Mendelspod Podcast

An inventor of Solexa sequencing by synthesis has a new idea.On today’s show, Sir Shankar Balasubramanian revisits the accidental origins of Solexa sequencing, born not from a sequencing project at all, but from curiosity-driven experiments watching DNA polymerase at work. What followed helped transform DNA sequencing from a specialized pursuit into a routine engine of modern biology. But as Shankar makes clear, the biggest surprise may not have been genomics itself—it was how next-generation sequencing became a universal readout for biology, powering everything from single-cell and spatial biology to entirely new ways of probing molecules and mechanisms.Our conversation then turns to his latest venture, Biomodal, and the emerging world of 6-base sequencing. Shankar explains why distinguishing 5mC and 5hmC matters, and how six-base sequencing may improve early cancer detection. 6-base sequencing could also aid researchers in the exciting frontier of neurobiology.As always with great scientists, the story widens beyond any single technology. Shankar closes by reminding us that discovery follows better measurement. As our tools improve, biology will continue to surprise us. “That is what research is. It’s stepping into the unknown,” he says. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

There’s a famous line attributed to Ernest Rutherford, the father of nuclear physics: “All science is either physics or stamp collecting.” It’s still provocative. But it’s unfair to biology. Long before today’s omics era, biologists were uncovering causality everywhere from evolution and natural selection to Mendelian inheritance. They have never merely catalogued life. They have explained it. But modern biology has also generated extraordinary inventories of genes, proteins, and pathways, and those inventories now invite a deeper systems-level question: how do the parts behave together in living cells? Could new precise physical measurements aid biology and medicine?Todays’ guest, Erdinc Sezgin, is an Associate Professor at Karolinska Institute and recipient of the Biophysical Society Early Independent Career Award. His lab is bringing physics to biology. For example, Sezgin studies the cell membrane not as a passive wrapper, but as an active, dynamic system whose physical properties of fluidity, viscosity, charge, and organization help determine how cells signal and survive. His hope is to improve ways to measure these biophysical properties.Sezgin discusses his recent collaboration with Pixelgen Technologies, where Molecular Pixelation was used to study how changing membrane charge reshapes the cell surface. By knocking out a lipid-regulating complex, Sezgin and his colleagues showed that living cells can adopt surface features that alter immune recognition and may help explain how cancer cells evade destruction. It’s a reminder that major biological insights often arrive hand-in-hand with new tools that make previously hidden phenomena measurable.The conversation closes on a broader point about scientific boundaries. Biology is not separate from physics or chemistry, but an expression of them in living systems.“Cells don’t have physics, chemistry, biology. . . It is life,” he says. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

You’ve heard of 5-base genomics. How about 6-base? It turns out that separating 5-methylcytosine (mC) and 5-hydroxymethylcytosine (hmC) is pretty important.Peter Fromen has had a front-row seat to the evolution of sequencing, from the rise of high-throughput genomics at Illumina to long-read technologies at PacBio. Now, as CEO of Biomodal, he’s focused on integrating genetics and epigenetics into a single workflow—and showing that the regulatory layer of the genome may be where the next breakthroughs lie.Chapters:0:00: Why epigenetics needed a reset12:07 The colorectal cancer study and early detection signal16:41 Building the 6-base ecosystem21:23 Commercial traction and the road to the clinicIn today’s program, Fromen explains why distinguishing between mC and hmC changes how we read biology. Biomodal’s recent colorectal cancer study begins to demonstrate that value in practice. “We ultimately ended up generating an AUC of 95%,” he says, describing early-stage detection results that point to the power of combining both signals. More broadly, he frames hydroxymethylation as an early indicator of disease.“hmC is essentially the canary in the coal mine for early disease detection.”We also discuss the practical side—what a 6-base workflow looks like in the lab and where the company sits commercially as it pushes toward clinical validation. Will this be the new standard for how we read biology? This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

What is the value of someone’s genome over their life? Is a genome today what it was 10 years ago? How does the adoption of genomic testing compare to other areas in medicine, such as imaging or electronic health records?Today we take a pretty comprehensive look at genomic testing in practice with Damon Hostin, Head of Market Access, Clinical Solutions at Illumina. Damon brings a rare perspective to this conversation. He’s been in the field since the Celera era, when sequencing was helping define modern genomics, and he’s also worked on the front lines in a large community health system, CommonSpirit Health. At Illumina, he speaks regularly with payers and other stakeholders.Across oncology, rare disease, reproductive health, and pharmacogenomics, Damon describes a field that has clearly moved into standard of care in key areas—but is still very much in the phase of identifying the “eligible but under-tested.” Adoption is real, but it’s incomplete.Chapters:0:00 Genomic medicine arrives4:51 Genomics, imaging, and the EMR11:23 Oncology—from diagnostics to decision-making18:16 Rare disease and reproductive genetics28:51 The lifetime value of a genome36:03 Cost, quality, and what a genome isA central idea running through the podcast is that the genome is no longer a one-time diagnostic. Its value compounds over time as databases grow, variants are reinterpreted, and new therapies emerge. At the same time, even the basic notion of what a “genome” is, is beginning to shift. With the rise of multi-omic data—transcriptomics, proteomics, methylation—the question is no longer just cost per genome, but what kind of biological insight we’re actually measuring. “A genome isn’t a genome isn’t a genome,” Damon says.He ends with a line that neatly reframes the entire debate around cost: “When you look at the cost of healthcare . . . the cost of the genomics is almost nothing.”Genomic medicine is here. We’re now wrestling with how to scale it, how to use it earlier, and how to make it part of the everyday infrastructure of care. Note: For more discussion and analysis on this topic, check out this upcoming Virtual Roundtable Discussion at GenomeWeb. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Fei Chen of the Broad Institute describes the original problem simply: genomics gave us powerful inventories of gene expression, while microscopy gave us structure—yet the two lived in separate worlds. “You could either have your structure or you could have gene expression, but you couldn’t have both.”In this conversation, Fei walks us through how Slide-tags—now commercialized as Takara Bio Trekker technology—set out to close that gap. Instead of mapping gene expression onto a grid, his team flipped the problem: barcoding the cells in place, then reading them out with single-cell sequencing. The result is something closer to a GPS system for cells.What this unlocks is not just better maps, but better biology. Better questions. In cancer, Fei describes the discovery of local immune “circuits” that determine whether tumors respond to immunotherapy. And more broadly, spatial data turns tissue itself into a kind of experiment itself. Is this the biology of the future? “The spatial context is a natural experiment that has happened.”Chapters:0:00 The problem: structure vs gene expression1:36 A GPS for cells8:59 Immune circuits and cancer response20:04 Tissue as experiment26:24 New questions for biologyAcross applications, Fei emphasizes that the real shift is conceptual. Spatial biology is not just about adding location to sequencing. It’s about learning how to ask new questions—ones that treat cells not as isolated units, but as participants in research. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Peptides are having a moment. But beneath the market excitement and the GLP-1 headlines, something more interesting is going on. A field that for years seemed technically promising but perpetually constrained is becoming wide open.To see into that open terrain, we’re joined by Charlie Johannes, founder of EPOC Scientific and president of the Peptide Drug Hunting Consortium, along with Tomi Sawyer, a founder of the Consortium and founder of Maestro Therapeutics. We asked them for a high-level look at a field being reshaped by advances in chemistry, screening, delivery, and by a growing sense that peptides may be uniquely positioned to open up biology that other modalities have only partly been able to reach.And yet both are clear: the field is not mature. AI is accelerating biology, which still depends on existing knowledge. Prediction remains limited, especially with non-natural chemistry. And the core challenge may now be human—how to turn an overwhelming amount of data into real innovation. As Johannes puts it, “Turning knowledge into innovation is the real challenge.”Chapters:1:31 Why peptides are suddenly hot again6:10 Between small molecules and biologics10:14 Oral delivery, screening15:45 AI, automation, and the limits of prediction32:17 The Consortium and where the field is headingThis is not a finished revolution—it’s a launch. The field, Sawyer says, is “in the Artemis II rocket right now heading towards the moon.” The peptide story is now much bigger than obesity drugs. Where does the field stand today? What has changed, and what remains difficult? This episode is the first in a new partnership between Mendelspod and Peptide and Protein News, a media platform covering peptide and protein drug development. You can see what they’re up to at peptideandprotein.com. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

It was the biggest story in sequencing last year: Mark Kokoris, head of SBX sequencing at Roche and inventor of the technology, joins Mendelspod to talk about how Sequencing by Expansion (SBX) works and why it may redefine the limits of genomics.* 0:00 A long journey inspired by PCR* 7:20 What is sequencing by expansion?* 14:00 On scale and accuracy* 19:40 Multi-omics vision?* 24:40 What will be the killer app?* 30:00 Biggest challenge for launchKokoris recounts the long path from co-founding Stratos Genomics in 2007 to Roche’s acquisition in 2020, when his team’s “wildly ambitious chemistry” finally found its match in Genia’s high-density nanopore platform. “Our approach to efficiently sequencing DNA,” he explains, “is to not sequence DNA. We rescale the problem—expand the molecule about 50-fold—so we can read it with much higher signal-to-noise.”The result is astonishing speed. Working with the Broad Institute and Boston Children’s Hospital, SBX delivered whole-genome results in under four hours, with the sequencing step itself taking only about 15 minutes. Kokoris attributes the achievement to a confluence of chemistry and compute.SBX’s duplex mode achieves Illumina-level accuracy (F1 > 99.8 %) while maintaining single-molecule simplicity. Its tunable flexibility lets small labs run a handful of samples in hours or large centers run thousands per day. Kokoris describes it as a technology built on impatience and rule-breaking, designed to give scientists options they’ve never had.Looking ahead to the 2026 research-use launch, he’s characteristically bold:“For me, success means SBX becoming the new standard in sequencing. Innovation can’t stop—it has to keep evolving, because biology is complex and we’ve got a lot more to do.”This show was originally published Nov 11, 2025. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Why do some animals live ten times longer than others?That question opens today’s interview with Steve Austad, Distinguished Professor at the University of Alabama at Birmingham and one of the leading thinkers in the biology of aging. It quickly becomes clear why he’s been such an important voice in bringing aging research from the margins into the center of science. As he puts it, the field was once “where scientists went to die,” but with modern genetic and molecular tools, it has become one of the most active areas in biomedicine.Steve’s approach, laid out in his book for the empiricist (I’m an amateur), Methuselah’s Zoo, is deceptively simple: look at the animals. From birds and bats to clams that live for centuries, he shows that lifespan follows a clear evolutionary logic. Safer, more stable environments favor slower aging. “If it’s unstable and unsafe… it makes sense… to reproduce fast,” he explains, while protected environments allow organisms to invest in long-term maintenance. It’s a framework that turns curiosity into theory—and theory into something testable.Chapters:1:31 Where scientists went to die4:11 The opossum problem8:00 Air, land, sea14:23 The longevity quotient33:30 Not forever, just longerWhat makes Steve such a compelling guide is his tone. He’s low-key, almost amused at times, but unwavering on the science. Aging, he reminds us, isn’t programmed for our benefit—“evolution does not care how long you live.” That doesn’t mean we can’t intervene. The field is now moving into human trials, even if key tools like aging clocks are still imperfect. He has little patience for talk of immortality—calling it “completely delusional.” Still, he’s optimistic. Adding a decade or two of healthy life—not forever—is the goal today. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Molecular residual disease, or MRD, has been part of oncology’s vocabulary for decades. But knowing something is there and being able to measure it precisely are two very different things. In today’s show, we explore how MRD testing moved from a long-standing clinical suspicion to one of the most consequential tools in modern oncology.Joining us on the program are Chris Hourigan, Director of the Fralin Biomedical Research Institute Cancer Research Center (DC) at Virginia Tech, bringing the academic and clinical AML lens, and Gary Pestano, Chief Scientific Officer at Biodesix, offering the industry and diagnostic development perspective.Hourigan reminds us that MRD itself isn’t new. What was missing were the tools. From counting cells under a microscope to flow cytometry and now highly sensitive molecular techniques including droplet digital PCR, MRD has evolved into a quantitative, actionable signal. Coming from the side of commercializing and scaling assays, Pestano underscores the central challenge of distinguishing meaningful signal from background noise. “There is a lot circulating in our blood. The key is what is meaningful, what is not meaningful,” he explains. Sensitivity alone isn’t enough. Target selection, bioinformatic filtering, validation at scale, and real-world reproducibility all determine whether MRD can truly guide care. The field is very much still work in progress, say both.Looking ahead, they point toward quantification as the next frontier. MRD is no longer just about detecting what remains. It’s about deciding what happens next.“We’ve been talking about MRD as if it’s a binary concept” says Hourigan. “I can imagine in the future, there’s going to be windows, and we will tune therapy to what comes next.”Thank you to Bio-Rad for sponsoring today’s show. Bio-Rad is your trusted partner for absolute quantification and reproducible results in oncology research. Bio-Rad helps you move from data to confident decisions. Learn more at bio-rad.com/oncology. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comFor two decades, tests like Oncotype DX have helped oncologists decide which early-stage breast cancer patients should receive chemotherapy. But those tools were designed mainly to predict early recurrence, leaving physicians with far less clarity about the risk that cancer might return years later.For today’s program, George Sledge, Chief Medical Officer at Caris Life Sciences, discusses new findings from the TAILORx trial showing how multimodal AI—combining molecular sequencing, digital pathology, and clinical data—can improve long-term prediction of breast cancer recurrence.Sledge explains that breast cancer recurrence may actually reflect two different biological processes unfolding over time. Molecular signals captured through RNA analysis appear most informative for predicting recurrence in the first five years, while computational analysis of digital pathology images becomes especially powerful for predicting recurrence later in the disease course.“The best results come from looking at multiple omic levels,” Sledge says, describing a shift away from single biomarker tests toward integrated biological analysis.

We began this podcast back around the time the ENCODE project announced that much of the genome was biochemically active. The big science project was undoing the tidy idea of “junk DNA,” and not without controversy. But activity is not the same as purpose. On today’s show, we move past the question of whether the non-coding genome does something and ask a more ambitious one: why has evolution retained so much genomic material unless it carries adaptive potential?Theral speaks with Sudhakaran Prabakaran, computational biologist at Northeastern University and founder of NonExomics, about his provocative new book, “Eclipsed Horizons: Unveiling the Dark Genome.” Drawing on his lab’s work cataloging more than 250,000 non-canonical proteins, Prabakaran argues that regions outside traditional gene definitions are constantly generating novel open reading frames—previously unrecognized proteins that may shape adaptation, speciation, and disease.Chapters:(00:00) Identical Genomes, Wildly Different Fish(04:00) The Dark Proteome Wakes Up(10:00) Protein Pop-Up Shops(20:00) Homo Minimus and the Space Thought Experiment(30:00) Precision Medicine Beyond the ExomeFrom rapidly diversifying cichlid fishes to human accelerated regions (HARs) of the human genome linked to schizophrenia, he makes the case that protein birth and death is continuous, cheap, and exploratory. In his framing, the “dark genome” functions less like debris and more like a flexible evolutionary sandbox—capable of producing latent biological parts that can be deployed under stress or even extreme environments like spaceflight.The book goes beyond ENCODE’s demonstration of activity and asks what that activity is for, crossing into that taboo in biology, teleonomic analysis. Weaving together proteomics, evolutionary biology, information theory, and even speculative extensions into space biology, Prabakaran suggests that genomes may be structured not just to preserve past adaptations, but to enable future ones.For those of you staying put on the ground, the implications are very tangible for precision medicine. His company NonExomics is using non-canonical protein signatures to stratify cancer patients and refine difficult diagnoses, arguing that the next wave of biomarkers may lie outside the exome.Provocative? Certainly. Grounded in emerging proteomics tools and real clinical cases? Also yes. This conversation probes directly into that mysterious future of biology. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

“We have been talking now for 15, 20 years about the diagnostic odyssey. That shouldn’t exist anymore. The new odyssey is the therapeutic odyssey.”That’s Stephen Kingsmore, president and CEO of Rady Children’s Hospital (he just announced his retirement), explaining the impact of a new genome mapping technology from Illumina.Whole-genome sequencing has transformed diagnosis, but some of the hardest pediatric cases persist because the structure of the genome has remained difficult to resolve. Today on Mendelspod, we cover Illumina’s newly launched proximity mapped reads, showing how long-range genomic context can be captured directly on existing Illumina sequencers and integrated into the lab workflow. The conversation traces how this added structural clarity is already improving diagnostic confidence and, critically, enabling highly precise n-of-1 therapies such as antisense oligonucleotides (ASOs).Olivia Kim-MacManus, a pediatric neurologist and ASO trial leader, shows how the new diagnostic precision directly feeds therapeutic design. “All of these genetic therapy approaches hinge on precise diagnostics,” she notes, emphasizing that allele-specific and haplotype-aware targeting is essential for ASOs and other emerging gene-based interventions.From the product and workflow side, Ali Crawford joins us as Senior Director of Science Research at Illumina, detailing how the technology works without requiring new instruments or complex workflows, eliminating the need for separate library preparation steps.“You just order the kit and go,” she says, highlighting how preserving spatial information on the flow cell unlocks variant calls and structural insight that were previously inaccessible with their standard short-read sequencing.When genome structure comes into better focus, treatments are no longer theoretical. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comCareDx is a company on the move. For years, they have been a bellwether in molecular diagnostics. Their early bet on gene expression testing in transplant medicine, their bruising fight over Medicare coverage, and their pivot into cell-free DNA monitoring have all reflected the growing pains of precision medicine itself.Now, under CEO John Hanna, the company looks less like a single-test diagnostics firm and more like a clinical ecosystem.Hanna brings an unusual vantage point. He began his career in health insurance before moving into molecular diagnostics—giving him insight into both innovation and reimbursement. That dual perspective shaped CareDx’s recent evolution: focus tightly on a defined clinical niche—transplantation—while expanding horizontally into the tools, software, and services that surround it.Today, CareDx operates across three segments: lab products (including high-resolution HLA typing kits using PCR, NGS, and nanopore), a growing software and patient solutions business, and its flagship genomics portfolio led by AlloSure, its donor-derived cell-free DNA assay. What distinguishes the company now is its “solution selling” approach—engaging transplant centers not just with a test, but with workflow software, quality reporting tools, specialty pharmacy, and EMR integration.“Our solution selling strategy is working,” he says today.At the scientific core remains the effort to replace invasive biopsies with molecular monitoring. AlloSure’s innovation—detecting donor-derived cell-free DNA without requiring donor genotyping—made routine blood-based rejection monitoring scalable. Yet adoption is not purely technical.“The biggest challenge with our space is building belief that molecular testing can replace tissue biopsy.”Clinician education, clinical trials, and guideline inclusion remain central to shifting standards of care. CareDx has leaned heavily into this, hiring medical leadership specifically to translate data into practice. The company is also layering AI on top of its molecular assays. AlloSure Plus integrates genomic results with EMR-derived clinical variables to generate a rejection risk score. CareDx’s operational mantra has been to put the burden of complexity on the company, not the clinician.

Large-scale genomics is back — and this time, it’s global by design.In this episode of Mendelspod, we return to the kind of ambitious, shared genomics project that helped define the field a decade ago. The Global Parkinson’s Genetics Program (GP2) has now genotyped more than 100,000 participants worldwide, with roughly one third of samples coming from historically underrepresented populations. That scale and diversity are already reshaping how Parkinson’s disease is studied — and how it may eventually be treated.My guests are Andrew Singleton, co-lead of GP2, and Ignacio (Nacho) Mata, a geneticist at Cleveland Clinic and founder of the Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD). Together, they describe how globally representative datasets are not a political aspiration, but a scientific necessity — especially in an era of precision medicine.Singleton explains that studying Parkinson’s across populations doesn’t just broaden participation; it increases scientific power. “The more we learn about individual populations, the more we understand about disease as a whole — and the more chances we have to come up with treatments for disease as a whole,” he says. Mata brings a complementary perspective from years of building Parkinson’s genetics infrastructure in Latin America. He emphasizes that without inclusion in genetic and biomarker research, entire populations risk being excluded from the next generation of molecularly targeted therapies. “If we don’t have our patients studied for genetics or biomarkers, then those patients will not have access to the new treatments,” he notes, adding that GP2 is designed to narrow rather than widen existing health disparities.We explores how GP2’s open-science structure has been key to its success and could serve as a model for other global research projects. GP2 has invested heavily in training and infrastructure so that researchers around the world can lead analyses locally, rather than simply contributing samples.As both guests make clear, this is only the beginning. With hundreds of thousands of samples committed and a new generation of globally distributed investigators, GP2 is laying the groundwork for biologically defined subtypes of Parkinson’s and for more precise diagnostics and disease-modifying therapies.When genomics gets big enough — and inclusive enough — scale itself becomes a discovery. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

What if the hardest part of scaling cell therapy turned out to be a materials problem not a biological one—and the solution looked like a sponge?On today’s show, Theral speaks with Yev Brudno, Associate Professor in the School of Pharmacy and also the Department of Biomedical Engineering at the University of North Carolina at Chapel Hill, about a deceptively simple technology that could dramatically accelerate manufacturing and lower the cost of cell therapies. Brudno’s lab works at the intersection of chemistry, biomaterials, and cell biology, with a focus on removing the manufacturing and scalability barriers that have kept powerful therapies like CAR-T out of reach for most patients.At the center of the conversation is a dry, porous biomaterial sponge—developed initially by accident—that boosts viral transduction efficiency from roughly 10% to as high as 90% by forcing cells and viral vectors into intense, highly efficient contact. The sponge works across multiple delivery systems, including retroviruses, lentiviruses, AAVs, and even lipid nanoparticles, effectively functioning as a low-cost, scalable alternative to complex microfluidic systems. Brudno explains how this discovery reframes genetic modification as a physical- and materials-science problem rather than a purely biological one.The discussion goes beyond mechanism into real-world impact. Brudno describes how these sponges—now commercialized for research use by Takara Bio USA—could compress weeks-long CAR-T manufacturing workflows into hours, enabling bedside or community-hospital cell engineering without the need for $100-million cleanroom facilities. The episode closes with a broader reflection on the future of cell therapy.Once again, some of the most transformative advances might come from curious bench science and happy accidents rather than prediction alone. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

For today’s show, we return to discussing the exciting new Cellanome platform. Joining Theral are Pier Federico Gherardini, VP of Computational Biology at Cellanome, and Matthew Spitzer, Associate Professor at University of California, San Francisco, whose lab is using Cellanome’s CellCage technology to study immune cells in dynamic, interactive contexts.0:00 From static snapshots to observing cell function in real time4:45 Pairing phenotype with function like we never could before7:30 Can see cell-cell interaction19:40 Early applicationsRather than relying on static single-cell snapshots, the Cellanome platform enables longitudinal observation of live cells—tracking division, interaction, and function over time—before pairing those behaviors with transcriptomic and molecular readouts. As Gherardini explains, “This creates essentially a new data type where you observe cells over time… and then you can pair all of that functional information with the molecular readouts that you get from sequencing.”For Spitzer, that shift fundamentally changes what can be known. Traditional approaches often force scientists to infer function indirectly, correlating phenotype measured in one experiment with behavior measured in another. With CellCage, his lab can finally measure both in the same individual cell. “Now we have measured the function of the cell and the phenotype for the same exact individual cell,” Spitzer says, “and this allows us to really understand how those core characteristics are linked in a much more detailed way.”For Spitzer, a major advance comes from observing cell–cell interactions as they unfold. Where previous methods could show proximity in a tissue section, they could not reveal outcomes. Using Cellanome, Spitzer’s team can now watch whether a T cell activated by a dendritic cell actually proliferates, produces effector molecules, or kills a tumor cell—and then trace those outcomes back to specific molecular programs. This has already revealed surprising heterogeneity within supposedly uniform cell populations, identifying rare but highly potent immune cells that would have been invisible in bulk assays.Looking ahead, both guests see immediate applications in cell therapy development, target discovery, and functional CRISPR screening—areas where measuring what cells actually do matters more than what they merely express. We close with a sense that cell biology is entering a new phase—one where function, interaction, and time are no longer inferred, but directly observed, measured, and modeled. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Half of oncologists in the U.S. are now ordering MRD testing, according to Adam ElNaggar, MD of Natera — but the other half, he says, “are still figuring out how to use it, or that it even exists.”In this episode, we talk with ElNaggar about the rapid rise of ctDNA-based monitoring and how it’s changing the very rhythm of cancer care. From Natera’s “tumor-informed” SignateraTM assay to its new “tissue-free” LatitudeTM test, the company is reshaping oncology around the molecular traces that cancer leaves behind.“ctDNA-negative patients have an extremely low likelihood of showing disease on imaging,” he explains. “So rather than scanning every few months, we can tailor follow-up to when it’s actually needed—and spare the anxiety and cost that come with it.”The conversation also covers Natera’s EmpowerTM hereditary cancer panel, which has expanded testing to all patients with ovarian and endometrial cancer, and a new Hereditary Cancer Alert program that nearly doubled testing rates among eligible patients. ElNaggar describes how hereditary and MRD testing now reinforce one another, helping clinicians catch missed cases and close the loop for families.We finish with a look ahead: a future where ctDNA status becomes a staging element, where clinical trials are shortened by molecular endpoints, and where multi-omic assays—combining DNA, methylation, and protein—push oncology toward truly personalized medicine.“We’re reaching the point,” says ElNaggar, “where staging won’t just be about pathology—it’ll be about biology.”Note about trials mentioned:IMvigor010 compared adjuvant atezolizumab to observation (surveillance) in an unselected muscle-invasive bladder cancer (MIBC) populationIMvigor011 prospectively randomized only ctDNA-positive MIBC patients to atezolizumab versus placeboSee all SignateraTM Publications here. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Aging may be the last great frontier of precision medicine—not a single disease, but the slow re-patterning of immunity, metabolism, and resilience that determines how well and how long we live.In this wide-ranging and genuinely mind-bending conversation, Alan Landay and Tom Blackwell make a compelling case that aging itself is finally becoming a legitimate—and testable—target of medicine.For Landay, the path into aging biology began decades ago through HIV. Antiretroviral therapy transformed HIV from a fatal disease into a chronic one—but something didn’t add up. Patients were surviving, yet developing cardiovascular disease, neurocognitive decline, and metabolic disorders years earlier than expected. The immune system recovered on paper, but inflammation never fully resolved. That realization led Landay to view HIV as a model of accelerated aging, and to ask whether the same inflammatory processes drive aging in the broader population. As he explains, “we realized that persistent inflammation was the driver—pushing comorbidities forward in time. That’s when HIV stopped being just an infectious disease and became a window into aging itself.”Over the past decade, Landay has brought the full toolkit of systems biology to that question—proteomics, metabolomics, glycomics, microbiome analysis, and epigenetic clocks—to understand why some bodies grow frail while others remain resilient. A central theme is the gut: age-related changes in the microbiome weaken the intestinal barrier, allowing inflammatory signals to leak into circulation and quietly accelerate biological aging.Blackwell approaches the same problem from the clinic. As a geriatrician, he sees that most people ultimately die from one of three conditions—heart disease, cancer, or dementia—and that aging is the common denominator behind them all. His bold question is not whether we can treat these diseases individually, but whether we can slow the biological aging process that gives rise to them. That question underpins his ongoing clinical trial testing tirzepatide, a GLP-1–based therapy, not for weight loss, but for its potential to slow aging itself. ““There is no drug in the world proven to slow aging,” Blackwell says. “We haven’t proven this one either—but we’re finally running the experiment that can give us a real answer.”At the heart of the discussion is a shared fascination—and healthy skepticism—around aging clocks and biomarkers. Both researchers are using advanced epigenetic and proteomic clocks, including the DunedinPACE measure, to track whether interventions truly change the rate at which people age biologically. The clocks are powerful, but not yet definitive. The episode also explores how geroscience has moved from the fringe to the mainstream: NIH-wide initiatives, ARPA-H funding, repurposed drugs, and growing FDA openness to aging as a trial framework. Rather than chasing immortality, both guests emphasize healthspan—more years of mobility, cognition, and social engagement. “Our vision isn’t to live longer in a nursing home. It’s having a lot more 98-year-olds who drive themselves to clinic, go on dates, and still love their lives,” says Blackwell. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comThe RNA revolution didn’t end with COVID. It’s only just beginning.Today Theral is joined by Andrew Geall, co-founder and Chief Development Officer of Replicate Bioscience, to explore why self-replicating RNA may represent the next major leap in vaccines and therapeutics. While first-generation mRNA proved what was possible in a pandemic, Andrew argues …

Perhaps more than in any other field, AI is impacting drug discovery and development. To begin the year we’re joined by two AI software-as-service companies, one on the target discovery side and the other built for new compound identification for those targets.Theral speaks with Aqib Hasnain, Product Lead at Mithrl, and Cheng Hu, co-founder and CEO of Technetium Therapeutics, about how scientists can go from AI generated insights to AI generated assets, from AI-driven fast science, to AI-driven fast drug discovery.Aqib describes Mithrl as a virtual lab partner focused on shrinking the time between experiments by letting scientists interrogate their own data directly. One of the biggest lessons in building Mithrl, he says, was how much transparency matters. Biologists need to understand the methodology through and through, and this translates directly to how Mithrl works.“Scientists need to be able to scrutinize and trace everything—because it’s their responsibility to make the next decision.”Cheng explains Technetium’s vision of an “AI-driven hatchery of novel medicines,” using design-based, physics-guided approaches to move from target discovery to small-molecule hits in weeks rather than years as has been the case screening libraries of millions of compounds. Reflecting on the promise of AI co-scientists, he points to the industry’s biggest unmet need. “There’s a very serious deficit of novel therapeutic targets and also a very serious deficit of novel chemicals.”Together, the conversation explores how these two AI tools for target discovery and hit generation are beginning to reshape drug discovery workflows—and how a new ecosystem of services is developing that is redefining the field. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

In our most listened to episode this year, Certis Oncology CEO Peter Ellman breaks down how his company is reinventing cancer research by building orthotopic patient-derived tumor models that more faithfully mimic human cancer — and using them to improve both drug development and treatment decisions. What is meant by orthotopic? That’s when patient tumors are placed in the “correct place” inside mice to create more faithful cancer models.Ellman shares the deeply personal origin story behind Certis and explains why their models have changed lives. He discusses the company’s AI-driven predictive platform, now patented, that aims to double drug success rates and usher in truly personalized oncology.Happy New Year 2026! This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

As sequencing continues to become cheaper, more attention is being paid to sample prep. Today we’re following up with the company, Volta Labs, a genomics applications company transforming sample prep for NGS by increasing robustness and precision, and lowering operating costs. CEO Udayan Umapathi reflects on what has been a breakout first commercial year for Callisto, the company’s sequencer-agnostic, digital-fluidics platform for sample prep. When he was last on the show, Callisto had just launched. One year later, it is deployed across North America, Europe, and Asia, with rapid uptake in clinical labs, pediatric oncology centers, and high-throughput sequencing sites.Udayan says the scale of adoption surprised even the team. “We said we wanted to be the front end of every sequencing technology. We’ve actually done that,” he notes, adding that more than ten applications now support short- and long-read sequencing.What’s driving the momentum? Three things keep coming up from customers: true walk-away automation, the ability to run any chemistry on any sequencer, and major improvements in quality and cost. Labs without automation engineers can now “simply buy a kit and run software…without having to learn sample prep,” Udayan explains.A standout story this year has been pediatric oncology, where whole-genome sequencing and hybrid-capture workflows have shown strong performance on Callisto. Customers such as Prinses Máxima Center and UMC Utrecht are using the platform across Illumina, Oxford Nanopore, Ultima, and other chemistries, achieving the sequencer-agnostic vision Volta set out from the start.Looking ahead, Udayan sees sequencing as still early in its evolution and believes sample prep has vast room for innovation. “One platform to do Illumina, one platform to do Oxford Nanopore, one platform to do Ultima… long read, short read—we do it all,” he says. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Few startups have launched with such quiet anticipation—or such a remarkable founding pedigree—as Cellanome. Backed by veterans of the genomics revolution, the company aims to do for cell biology what Illumina did for sequencing: make it measurable, dynamic, and multidimensional.In this debut conversation, Cellanome CEO Omead Ostadan traces his path from the early days of Applied Biosystems and Solexa to what he calls “the multi-omics of the cell.” He describes a breakthrough platform capable of observing living cells in real time, combining imaging, molecular analysis, and computation in ways that bring biology closer than ever to its native state.“Our hypothesis,” says Ostadan, “is that you are now creating an environment that most resembles the natural environment in which these cells operate. Anything you’re measuring is much more likely to resemble what you’re going to see in real biology.”Using what the company calls CellCage technology, the Cellanome R3200 system can isolate and sustain thousands of living cells or co-cultures—neurons with microglia, for instance—allowing researchers to track interactions, responses, and phenotypic changes over time. Ostadan believes this kind of structured, longitudinal, multimodal data will be foundational for the next generation of AI-driven biological models.“The next leap in biology,” he says, “requires a fundamentally different mode of data. That has been our focus from the start—to generate data that most closely resembles what’s happening at the foundational basis of biology across all organisms.”Now in full commercialization, Cellanome has multiple units installed in the U.S. and preparing for expansion into Europe and Asia. For Ostadan, who has helped bring multiple life-science platforms to market, this moment feels singular: “I’ve never been as excited about the potential of a technology as I am about what we have at Cellanome,” he says. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

At the end of each year we look for a guest who in many ways defines the year. Today we sit down former NHGRI director Eric Green to reflect on the most turbulent year in his 31-year career at NIH. After leading the National Human Genome Research Institute for more than 15 years, Green’s appointment was abruptly non-renewed—a decision he learned about with “two or three days notice that I was going to have to retire from federal service.” What followed, he says, was a wave of terminations and forced retirements across NIH that left NHGRI “in trauma” as entire communications, education, and policy groups disappeared overnight.Yet alongside this institutional upheaval, Green describes a scientific landscape moving at astonishing speed—from the maturation of genome editing and long-read sequencing to the rise of multi-omics and the accelerating push toward routine healthy newborn genome sequencing. He believes widespread newborn sequencing is no longer a distant vision but “within striking distance,” driven by global studies, new U.S. programs, and rapidly falling costs.The conversation also explores the political pressures shaping genomics today, especially around the collection of heterogeneous genomic data and the cultivation of a diverse workforce. Green argues that scientists must learn to explain their work in human terms—as stories about patients and cures, not grants and budgets. He says it might also be a good idea to not use the “d” word (for example, “assortment” rather than “diversity”) in grants for now, silly as that is.Despite the personal and institutional losses of the past year, Green remains committed to the future of U.S. biomedical science which continues to surge in the headlines each day. In a reference to Dickens, he says it is literally the best and worst of times.Now entering what he calls “version 3.0,” Green sees his role as genomics evangelist, educator, and advocate—helping ensure that the momentum of genomic medicine continues even as the nation’s scientific infrastructure undergoes profound stress.“I am officially on call to help rebuild the NIH… It’s very easy to destroy a place, and very hard to rebuild it.” This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Note: This show was originally published on September 11, 2025. In light of the recent acquisition of Foresight Diagnostics by Natera, we’re re-publishing the interview with co-founders Jake Chabon and David Kurtz.Catching a cancer relapse before any scan could see it is the ultimate goal for minimal residual disease or MRD testing. And it’s the promise behind Foresight Diagnostics, a Stanford spin-out co-founded by scientist Jake Chabon and oncologist David Kurtz who say they have arrived at “next gen” MRD testing. In this debut interview, Jake and Dave walk us through their journey from academic research to launching one of the most sensitive MRD tests on the market—one that’s already shaped new NCCN guidelines.* 0:00 Origin story* 4:45 What makes this “next gen?”* 10:15 How do you get the leap in sensitivity* 15:45 Already had an impact on NCCN guidelines* 23:00 Launching lymphoma texting next year, then on to solid tumors* 28:00 How will this change standard of care?Jake explains how their novel PhasED-Seq technology, which tracks “phased variants”—usually two or three mutations on the same DNA molecule—enables unprecedented sensitivity, detecting cancer cells at levels as low as one part in 10 million. “It’s extremely unlikely to have two concurrent sequencing errors,” says Jake. “That’s functionally the core insight here.”For Dave, who still treats lymphoma patients, the clinical need is personal. “Our goal is to treat patients until there are no more cancer cells in the body. So having a tool that tells you when there are no more cancer cells left is kind of our holy grail.”Their MRD test, called Foresight CLARITY, launches first for lymphoma next year, with solid tumor applications in development. As their data have already begun to reshape the standard of care, Jake and Dave discuss a future in which MRD testing could come before PET scans—or even replace them.“We want MRD testing to become the standard of care across all cancers treated with curative intent,” says Jake. With Foresight CLARITY already in three prospective trials and in NCCN guidelines, and a clear clinical need, that vision may not be far off. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

This week on Mendelspod, we speak with Petter Brodin, Professor of Pediatric Immunology at the Karolinska Institutet and Director of Systems Immunology at Imperial College London, about his pioneering work in childhood immune development and his new spatial-proteomics investigations into lupus.Petter shares how a single lecture on natural killer cells pulled him into immunology, and how early twin studies convinced him that “our immune systems are shaped predominantly by non-heritable factors.” That insight drove him to study the earliest stages of immune development—when newborns leave a sterile environment for a microbial world that imprints their immune trajectories for life.A major theme of the conversation is Petter’s insistence that immune responses cannot be understood by looking at cells one by one. As he puts it: “Cells don’t ever work in isolation, but historically we’ve always been studying them in isolation—and I think that’s fundamentally problematic.”This systems view is now being partly enabled by Pixelgen’s spatial interactomics. Using their Proximity Network Assay, Petter’s group is finding that lupus B cells don’t just differ in protein expression—they differ in protein distribution, revealing organization patterns that classical flow cytometry cannot capture.These spatial signatures may point directly to new, more precise therapies. Petter explains: “If there is a difference in protein–protein interaction or protein distribution that characterizes disease, then surely that indicates a dysregulation—and that is something we can target.” Instead of broad immunosuppression or depleting whole cell populations, future treatments could focus on the exact cell states driving autoimmunity.Petter ends on an optimistic note: spatial interactomics won’t just help treat autoimmune disease—it may allow us to intervene earlier, even preventatively, as we learn how early-life immune disturbances set the stage for disease decades later. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

What if the next leap in human health isn’t hidden in our genes, but in everything that happens to them? In this week’s truly groundbreaking Mendelspod episode, we open a new chapter for the show: our first deep dive into exposomics—the study of all the physical, chemical, biological, and social exposures that shape the human body across a lifetime.To guide us, we welcomed two leaders at the center of this emerging field: Chirag Patel of Harvard and Gary Miller of Columbia University, fresh off organizing Genomics Meets Exposomics, a landmark meeting held at the Mendel Museum in Brno—the birthplace of modern genetics. In the same abbey where Mendel tended pea plants, genomics and exposomics researchers from Europe and the U.S. gathered for the first time to build a shared roadmap for understanding how genes and environment interact to drive disease.In our conversation, Chirag and Gary explain why the genome alone can’t answer the biggest questions in human health. While genomics accounts for roughly 20% of complex disease risk, the remaining 80% lies in our exposures—pollutants, diet, geography, stress, microbes, medications, and more—and the fingerprints these exposures leave on our biology. Exposomics, as Gary notes, is about moving from studying one factor at a time to systematically measuring the thousands of signals that accumulate in our tissues and blood.A major theme of the discussion—and the inspiration for our episode title—is Chirag Patel’s call for exposomics to follow the same playbook that transformed genomics in the early 2000s. Just as genome-wide association studies (GWAS) revolutionized how we identify genetic contributors to disease by moving beyond one-gene-at-a-time thinking, Patel argues that the field now needs exposome-wide association studies (EWAS) to systematically search for environmental drivers. “If we are to do an exposome-wide association study… we can now discover things that were missing,” he explains, shifting from narrow, candidate-factor approaches to broad, data-driven discovery.Both guests describe a field gaining momentum thanks to better measurement technologies, large biobanks, geospatial data, and new analytic frameworks inspired by genome-wide association studies. They also speak frankly about the remaining hurdles. As Chirag puts it, one of the major challenges is not just correlating exposures with disease but determining what these findings mean for people: “There’s a number of questions that come after that…how do you modify it? Is it causal? How do we remove it from the population if it’s adverse?”Gary, who has spent decades studying Parkinson’s and Alzheimer’s, explains how high-resolution mass spectrometry now allows researchers to see exposure signals that were invisible before—sometimes even in decades-old blood samples. And looking ahead, he offers a clear note of optimism about exposomics’ readiness for scale: “We can do this now. It’s a reality.”For long-time Mendelspod listeners, the episode marks an inflection point. After fifteen years covering genomics and the multi-omic revolution, this conversation shines a light on the other half of human biology—the environment—and what may become the next major frontier in disease prevention, drug development, and precision health. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

After more than a decade of success in research, long-read sequencing is more and more adopted into clinical testing. In today’s show, we speak with Rita Shaknovich, Chief Medical Officer at Agilent Technologies, and Sarah Kingan, Associate Director of DNA Applications at Pacific Biosciences (PacBio), about how their collaboration is speeding up this long-anticipated transition.* 0:00 Long read sequencing changing clinical landscape* 7:00 Long reads replacing older technologies* 13:15 Agilent/PacBio partnership – speeding up adoption* 16:00 Panels designed for short reads can be used for long reads* 24:25 Democratizing accessLong-read sequencing—once prized mainly by researchers for its ability to resolve structural variants, repeat expansions, and complex genomic regions—has reached a point of technical and economic maturity that now makes it viable in the clinical setting. “We can now see regions of the genome that were long considered dark matter,” says Shakhnovich. “That’s leading to improved diagnostic yield and, most importantly, better outcomes for patients.”Agilent brings to this collaboration a long-standing foothold in laboratory testing. Its automated platforms and target enrichment chemistries are already embedded in many diagnostic laboratories worldwide. PacBio, of course, brings the power of HiFi long-read sequencing to the table. Together, the companies are demonstrating that technologies originally designed for short-read sequencing can be seamlessly adapted to long-read workflows. “Panels that were designed for short reads can be used for long reads—essentially right out of the box,” explains Kingan. “It really just opens up a whole world of clinical applications immediately.”By combining Agilent’s infrastructure and expertise with PacBio’s long-read innovation, the partnership is accelerating the integration of comprehensive, single-platform sequencing into patient testing. The result is a streamlined, cost-effective approach that reduces the need for multiple assays while providing richer genomic insight. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

What used to take months of bioinformatics analysis can now happen in minutes—and with greater biological insight than ever before. In this episode, Theral Timpson sits down with Vivek Adarsh, co-founder and CEO of Mithrl, an “AI science” company that’s bringing the power of vertical AI to the lab bench.Adarsh began his career at Nvidia, long before the company became synonymous with AI. “What I learned there,” he recalls, “was that when you build a team around exceptional talent, deep passion, and empathy—especially empathy for your customers—everything else flows from that.” That lesson guides how Mithrl now builds tools for scientists drowning in data.At the heart of Mithrl is a platform that takes scientists from raw data to biological insight in minutes, complete with automatic data cleaning, literature integration, and a conversational interface. Adarsh describes how one pharma team identified new biomarkers in 15 minutes—a process that would normally take months—and how another user avoided a costly error when Mithrl’s reasoning layer caught an incorrectly labeled sample.Asked about the risk of losing “happy accidents” in a world of faster science, Adarsh pushed back:“AI doesn’t eliminate the happy accident—it multiplies the opportunities for it. You can’t control luck, but you can create the conditions for it to appear more often.”In closing, he offered a glimpse of what drives him:“If we can accelerate the path from raw data to real discovery—from sequencing files to the next therapy—then we’ve done something far bigger than building software. We’ve built a partner for science itself.” This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

The biggest story in sequencing this year lives up to the hype. Mark Kokoris, head of SBX sequencing at Roche and inventor of the technology, joins Mendelspod to talk about how Sequencing by Expansion (SBX) works and why it may redefine the limits of genomics.* 0:00 A long journey inspired by PCR* 7:20 What is sequencing by expansion?* 14:00 On scale and accuracy* 19:40 Multi-omics vision?* 24:40 What will be the killer app?* 30:00 Biggest challenge for launchKokoris recounts the long path from co-founding Stratos Genomics in 2007 to Roche’s acquisition in 2020, when his team’s “wildly ambitious chemistry” finally found its match in Genia’s high-density nanopore platform. “Our approach to efficiently sequencing DNA,” he explains, “is to not sequence DNA. We rescale the problem—expand the molecule about 50-fold—so we can read it with much higher signal-to-noise.”The result is astonishing speed. Working with the Broad Institute and Boston Children’s Hospital, SBX delivered whole-genome results in under four hours, with the sequencing step itself taking only about 15 minutes. Kokoris attributes the achievement to a confluence of chemistry and compute.SBX’s duplex mode achieves Illumina-level accuracy (F1 > 99.8 %) while maintaining single-molecule simplicity. Its tunable flexibility lets small labs run a handful of samples in hours or large centers run thousands per day. Kokoris describes it as a technology built on impatience and rule-breaking, designed to give scientists options they’ve never had.Looking ahead to the 2026 research-use launch, he’s characteristically bold:“For me, success means SBX becoming the new standard in sequencing. Innovation can’t stop—it has to keep evolving, because biology is complex and we’ve got a lot more to do.” This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

What company began as a sake manufacturer over a century ago and went on to launch the world’s first single-cell kit in 2011? It’s Takara Bio—and their story is far from finished.In this episode, we talk with Dr. Andrew Farmer, Chief Scientific Officer and Head of R&D at Takara Bio USA, about the company’s remarkable evolution from a Japanese enzyme maker to a global innovator in single-cell and spatial biology. Farmer recalls, “We go way, way back to being a sake manufacturer a hundred years ago. And it’s through that business—realizing that sake is basically fermentation—that we could use that to do other interesting things in biology.”* 0:00 Began as a sake manufacturer over 100 years ago* 5:25 First kit for single-cell sequencing* 11:10 Bought Curio Bioscience to bring in spatial omics* 15:00 Returning to the level of the cell* 26:40 The new “T-cell sponge”He describes how Takara Bio introduced the first commercial single-cell reagent kit long before the current explosion of single-cell technologies: “The first single-cell reagent kit on the market was actually from us. That was in 2011, and even the Fluidigm C1 system was driven by our chemistry.”The conversation then moves through Takara’s acquisition of Curio Bioscience, adding the Trekker and Seeker spatial platforms, which—remarkably—require no specialized instruments. Farmer explains how this simplicity could democratize access to spatial data and accelerate multiomic studies in cancer and drug discovery.And for an ending twist, he introduces the “T-cell Sponge,” a porous hydrogel matrix that activates and transduces T cells in a single step—an innovation recently named one of The Scientist’s Top Innovations of 2025. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

When should a genetic test be ordered—and who decides? It’s a question we are constantly asking on the program. Dr. David Braxton, Chief of Molecular Pathology at Hoag Memorial Hospital in Southern California, has built a system where the answer is simple: the pathologist decides. At Hoag, reflex testing protocols automatically trigger genomic tests when certain cancers appear under the microscope—embedding precision medicine directly into the biopsy workflow.* 0:00 How did you become an advocate for precision medicine?* 5:50 What triggers the ordering of a genetic test?* 12:00 Using national lab vs in-house* 19:03 Which areas show most progress?* 24:32 A fan of early cancer testing?* 29:42 How digitized is your lab?* 42:45 Moonshot? Treat CHIP“We developed standardized operating procedures where if a pathologist sees certain types of cancers in certain states, they automatically order the genomic testing,” Braxton explains. “It’s all very formalized. We call it pathologist-initiated reflex testing—and it gets results into the medical record before the oncologist even sees the patient.”Braxton talks about making genomic profiling routine in a community setting, the barriers that still slow precision medicine—education, reimbursement, regulation—and how digital pathology and AI are reshaping what pathologists can see and do. “The real value of digital pathology and AI,” he says, “isn’t necessarily helping pathologists do their jobs quicker or better—it’s going beyond what the human eye can see.”Braxton offers a pragmatic, hopeful look at how community hospitals can lead the next phase of precision oncology. We discuss the increasingly used MRD testing and get Braxton’s thought’s on early cancer detection tests. In the end, he shares his “moonshot:” using molecular diagnostics to detect clonal hematopoiesis, a precursor state that silently increases risk for leukemia, heart disease, and other inflammatory conditions. “If you want to talk about the role of diagnostics in decreasing chronic conditions like heart attacks and cancer,” he says, “this is the moonshot—catching that silent killer early with molecular techniques.” This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Illumina has just made a bold move into proteomics.In this episode of Mendelspod, Krishna Morampudi, Associate Director for Product Management at Illumina, joins Theral to talk about the company’s recent definitive agreement to acquire SomaLogic and the new launch of Illumina Protein Prep, their new end-to-end proteomics solution.0:00 On the acquisition of SomaLogic4:30 Scoop: Illuminated Protein Prep just launched8:00 Competitive edge14:15 The larger multi-omics visionIllumina’s new product can screen for 9,500 proteins using SomaLogic’s SOMAmer technology, with sequencing on NovaSeq and data processed through Illumina’s existing connected analysis platforms. According to Morampudi, the integration with Illumina’s NGS workflows gives researchers a competitive edge and lowers the barrier to proteomics adoption.The product has already launched with early access customers, including large biobank studies such as UK Biobank through partnerships with Decode Genetics. Krishna notes that “the motivation to buy the company was really coming from working with those early access customers.”With a vision to make large-scale quantitative proteomics standard in discovery research, Illumina is betting that SomaLogic’s scalable, high-throughput tech can eventually outpace long-established competitors.“We’re starting with 9,500 proteins with lower CVs than Olink. Our ability to scale faster to the entire native proteome gives us a real advantage,” Morampudi says.In the final segment, Morampudi connects the proteomics launch with Illumina’s broader multi-omics vision and outlines the potential for new biomarker discovery, PQTL analysis, and phenotypic insights. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comOn today’s debut interview with Truvian Health, CEO Jay Srinivasan lays out the company’s bold but grounded plan to radically decentralize blood testing. With over $150 million raised and a benchtop instrument already in FDA review, Truvian aims to run 34 lab-quality tests from just eight drops of blood—in under 30 minutes.“Why does your blood have to t…

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comPremal Shah says that many companies in personal genomics have emphasized quantity over quality. Premal is the CEO of Myome, a company offering whole-genome interpretation built for the clinic rather than the consumer. Shah says Myome was founded on the belief that more data isn’t better data. “Physicians don’t want a laundry list of genes,” he told us …

A few weeks back we featured a next gen PCR technology called iconPCR that carries the promise to dramatically impact research. Today we take a customer’s-eye view of the technology. Dr. Stefan Green, who directs the Genomics and Microbiome Core Facility at Rush University, has been putting the instrument through its paces on challenging projects ranging from pathogen surveillance in Chicago to ultra-low biomass cleanroom samples for NASA. “PCR is both the greatest and worst invention of all time,” he says. “It’s empowered everything in molecular biology, but it introduces biases and artifacts. With iconPCR we finally have adaptive cycling that lets us stop at the right point for each sample.”Joining him is Yann Jouvenot, Senior Director of Product at n6, who explains how the company designed iconPCR’s AutoNorm technology to take the guesswork out of amplification. “PCR is to genomics what the printing press was to knowledge,” he says. “But unlike a press, PCR doesn’t produce identical copies at cycle two and cycle twenty-five. With iconPCR we’re helping scientists cut cycles before artifacts creep in, which means more accurate data and a better chance for every molecule to be represented.”* 0:00 “I wanted a device like this a decade ago.”* 6:41 PCR, the greatest and worst invention* 10:20 The “slope” method* 18:00 Protecting small samples* 28:45 Impact on research?Together they paint a picture of a deceptively simple but transformative innovation: a thermocycler that adapts in real time, reduces artifacts, saves time and labor, and improves the quality of genomic data. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Alex Dickinson, former Illumina executive and now host of The Geonomics Podcast, joins us for a wide-ranging conversation on the state of DNA sequencing and its future. Known for his independent voice, Alex isn’t afraid to speak plainly about the industry’s biggest players and its shifting technology landscape.* 0:00 Squarely in the long read age* 6:10 When short reads, when long?* 9:20 Whole genome testing* 15:00 Targeted long reads* 19:40 Roche’s new technology* 23:00 Multiomics: the bigger picter* 26:50 “I love MRD!”Our focus today is the economics of short reads versus long reads, the unexpected dominance of liquid biopsy, and why long reads are proving indispensable in cancer and rare disease diagnostics. He uses an illuminative metaphor.“The genome is like a jigsaw puzzle. With short reads, you’re stuck with thousands of tiny sky-blue pieces—it’s ambiguous. With long reads, you get bigger chunks, and suddenly you can see where the pieces belong. That’s how you detect the real structural changes in cancer,” he explains.Alex also dives into the new technology from Roche, weighing their disruptive potential. Beyond sequencing, he highlights the surge in multi-omics, particularly proteomics, and the gap between fast-moving diagnostics and available therapies. “Diagnostics is now ahead in many ways. In MRD especially, we can double progression-free survival if we catch cancer’s return early. The question is, do we have enough therapies to act on all this new information?” This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

In a time when many diagnostics companies are struggling, GeneDx is thriving by focusing squarely on solving one of medicine’s most pressing problems: the diagnostic odyssey for rare disease. CEO Katherine Stueland explains why the company has committed to whole exome and genome testing as first-line answers for children, and how their recent acquisition of Fabric Genomics expands their reach into AI-powered interpretation services.* 0:00 Success coming from a focus on rare disease* 5:20 Why whole genome testing?* 13:30 “No margin, no mission”* 15:50 Acquiring Fabric Genomics* 26:10 Bullish on healthy newborn screening“We’ve been focused on solving the fact that it still takes, on average, five years for a child with a rare genetic disease to get a genetic test and an accurate diagnosis. That’s something we can now provide within weeks, if not days, if not 48 hours.”On newborn screening, Stueland points to the GUARDIAN study at Columbia as a model: “What we’ve been able to find is a diagnosis in 3.2% of these otherwise healthy newborns. And the average age of diagnosis for those same conditions, in GeneDx’s 25-year history, had been 7 to 11 years. We’re now able to find them at birth.”From shortening the time to diagnosis to embedding genetic testing in general pediatrics, GeneDx is showing what it looks like to deliver on the promise of genomics in everyday medicine. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comFew founders get to build the future of genomics twice—Moran Snir is doing it a fourth time. After founding Clear Genetics and helping Invitae scale genetic services, she’s back with a new venture: Nest Genomics, a software platform aiming to make genomic care routine across U.S. health systems.* 0:00 Founder of four genomic medical companies* 6:55 When sho…

The story of Certis Oncology begins with a patient. In 2012, Barney Berglund was diagnosed with a rare sarcoma. Standard treatments failed him, and though his doctors at UCLA tried to create mouse avatars of his tumor to test drugs, Barney passed away before the models were ready. Out of his family’s grief came a mission: to change the trial-and-error nature of cancer treatment. They joined with physician-scientists and entrepreneur Peter Ellman to found Certis.* Chapters:* 0:00 What are PDx models?* 6:30 Orthotopic experts* 10:45 Success stories* 18:45 Winning an AI patent* 23:40 Business model* 27:40 The future will be so differentSince then, Certis has become the orthotopic experts—placing patient tumors in the “correct place” inside mice to create more faithful cancer models. These avatars don’t just support research, they’ve helped extend lives. Peter tells the story of one patient who came to him simply hoping to live long enough to dance with his daughter at her wedding. Thanks to Certis’s avatars, he did.Today, the company is pushing further. They’ve built a tumor bank nearly as large as the NCI’s and, most strikingly, just won a patent for their AI platform. “Patents in AI are rare,” Peter told me. “To us, this one isn’t just a legal win—it’s recognition that our predictive platform is novel and fundamental to how oncology will be done in the future.”Ellman imagines a not-so-distant future where drug success rates could rise from 10% to 50%, creating a world where “standard of care gives way to truly personalized medicine.”Sponsor: This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

For his first interview as CEO of Myriad Genetics, Sam Raha joined us to help kick off Mendelspod’s 15th season. Raha, who took the helm in April after serving as COO and holding senior roles at Illumina and Agilent, leads Myriad at a pivotal moment. While consumer genomics has faltered—23andMe filed for bankruptcy earlier this year—Myriad continues to double down on its clinical strategy with new offerings in oncology, prenatal testing, and mental health.* 0:00 New MRD and HRD testing* 5:30 What has you excited?* 9:32 Great numbers year after year - what’s your secret sauce?* 16:00 “A long way to go” on physician education* 20:15 Thoughts on DTC?* 23:40 First test using AI* 27:00 The decade aheadMyriad has announced strong financials and a robust pipeline, including its first AI-powered test for prostate cancer launching in early 2026 and a proprietary minimal residual disease (MRD) test slated for mid-2026. “We’re still in the early innings of the golden age of genomics,” Raha said. “What excites me is taking a brand that’s well-known in our space and really having the company live up to its potential.”In this wide-ranging conversation, Raha discussed what he sees as Myriad’s “secret sauce” for steady growth, the need for greater physician education—“we have a long way to go”—and his vision of combining genomics with imaging, proteins, and AI over the next decade.“Success is not just the numbers,” he emphasized. “We can grow in the low double digits profitably, while being a company that patients, providers, and employees are proud to work with.” This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Catching a cancer relapse before any scan could see it is the ultimate goal for minimal residual disease or MRD testing. And it’s the promise behind Foresight Diagnostics, a Stanford spin-out co-founded by scientist Jake Chabon and oncologist David Kurtz who say they have arrived at “next gen” MRD testing. In this debut interview, Jake and Dave walk us through their journey from academic research to launching one of the most sensitive MRD tests on the market—one that’s already shaped new NCCN guidelines.* 0:00 Origin story * 4:45 What makes this “next gen?” * 10:15 How do you get the leap in sensitivity * 15:45 Already had an impact on NCCN guidelines * 23:00 Launching lymphoma texting next year, then on to solid tumors * 28:00 How will this change standard of care?Jake explains how their novel PhasED-Seq technology, which tracks “phased variants”—usually two or three mutations on the same DNA molecule—enables unprecedented sensitivity, detecting cancer cells at levels as low as one part in 10 million. “It’s extremely unlikely to have two concurrent sequencing errors,” says Jake. “That’s functionally the core insight here.”For Dave, who still treats lymphoma patients, the clinical need is personal. “Our goal is to treat patients until there are no more cancer cells in the body. So having a tool that tells you when there are no more cancer cells left is kind of our holy grail.”Their MRD test, called Foresight CLARITY, launches first for lymphoma next year, with solid tumor applications in development. As their data have already begun to reshape the standard of care, Jake and Dave discuss a future in which MRD testing could come before PET scans—or even replace them.“We want MRD testing to become the standard of care across all cancers treated with curative intent,” says Jake. With Foresight CLARITY already in three prospective trials and in NCCN guidelines, and a clear clinical need, that vision may not be far off. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Epigenetics has emerged as one of the most revealing windows into cancer biology. Long before genetic mutations appear, changes in DNA methylation can initiate tumorigenesis, shape tumor diversity, and provide powerful clues for biomarker discovery.In this episode of Mendelspod, we explore Illumina’s new 5-base solution with Dr. Bodour Salhia, a cancer epigenetics researcher at USC’s Keck School of Medicine, and Danielle Goldberg, senior product manager at Illumina. The conversation brings together the researcher’s perspective and the technology developer’s vision on how this advance could reshape cancer research.Dr. Salhia explains why DNA methylation is such a powerful lens into cancer biology:“DNA methylation is fundamental for regulating gene expression and maintaining genome integrity. It’s also one of the earliest tumorigenic events that often precedes genetic mutation.”She details the challenges of older methods like whole-genome bisulfite sequencing and why her lab was eager to test the new workflow.Goldberg describes what makes Illumina’s 5-base solution a leap forward:“It’s a single assay that gives you dual insights—one library prep, one sequencing run, and an analysis pipeline that enables the detection of both genomic variants and methylation with high accuracy.”Together, they discuss how combining genetic and epigenetic information in one streamlined workflow not only increases efficiency and reduces cost but also eliminates biases introduced by multiple assays. The result, they say, is a more integrated view of cancer biology and more accessible research at a time when budgets are tightening.Looking ahead, both Salhia and Goldberg envision deeper integration of genomic and epigenomic data accelerating discovery and biomarker development.To learn more about Illumina’s 5-base solution, tune into an upcoming webinar here. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Reinventing PCR, huh? That’s what we asked Pranav Patel, CEO and co-founder of N6 Tec, on today’s show. After all, PCR is one of the oldest tools in the molecular biology toolbox. Isn’t that field… done?Turns out, not at all.Patel — a veteran of PacBio, 10x Genomics, and founder of 2D Genomics — is back with a bold rethink of thermocycling itself. His new platform, IconPCR, isn’t just another black box with 96 wells. It’s the first of its kind to feature independently controlled wells, enabling real-time amplification, quantification, and normalization — all in a single run. If PCR was once just about making more DNA, IconPCR is about making just the right amount, at just the right time — and eliminating the variability that can quietly wreck your sequencing before it even starts.“Instead of me telling it how many cycles, I can tell it how much DNA I want — and it will determine the cycles by itself. That’s the fundamental shift,” he says.But maybe the bigger shift is cultural — a refusal to treat sample prep as solved, and a willingness to build new tools for today’s applications, not yesterday’s.“It gets branded as a PCR machine. But honestly, the capability of it is so much more. It does what would otherwise take multiple instruments — and it does it from day one.”With a blend of unaffected humor and technical rigor, Pranav walks us through the frustration that led to this innovation, the simplicity of the idea, and the engineering feat that makes it possible. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

Today we sit down with renowned geneticist David Ledbetter, whose pioneering work helped uncover the chromosomal basis of Prader-Willi, Angelman, and Miller-Dieker syndromes. He served as Chief Scientific Officer at Geisinger, where he led the MyCode Community Health Initiative—one of the largest population genomic screening programs in the world. Now, he's bringing his decades of experience to bear on a bold new initiative: the Institute for Pediatric Rare Diseases at Florida State University.Funded through Florida’s landmark Sunshine Act, the new institute is part of a broader vision to create a statewide pediatric genetics network and pilot universal newborn whole genome screening. Ledbetter walks us through how this model could reshape not only early diagnosis but the entire standard of care for children with rare genetic conditions.* 0:00 From 5 to 50% rare disease diagnosis* 4:00 The MyCode story at Geisinger* 7:00 Leading the new pediatric rare disease institute at FSA* 11:20 Moving closer to universal newborn screening* 20:20 More information is better* 34:00 WGS as universal platformLedbetter is bullish on whole genome sequencing (WGS) as the foundation for future genetic testing:“Whole genome sequencing is becoming the universal platform for genetic testing. That greatly simplifies testing—physicians no longer need to know dozens of platforms. They just need to provide good clinical info, and we’ll handle the rest.”He also makes the ethical case for early diagnosis as a matter of patient rights:“If you really have a genetic technology that can identify every rare genetic disease individual at birth, that child has the right to be found.”From the cost and logistics of trio testing to the promise of AI in variant interpretation, this conversation offers a powerful glimpse into where rare disease diagnosis is headed—and why Florida may be leading the way. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

In this special tribute episode, Mendelspod honors the life and legacy of Dr. Atul Butte (1969-2025), a towering figure in big data and precision medicine who passed away earlier this year. Atul was more than a pioneer in translational bioinformatics—he was a mentor, a builder, and a boundless source of ideas. He sought to “lift all boats in the harbor.”Joining the conversation are three scientists who worked closely with him and continue to carry forward his vision:* Dr. Marina Sirota, UCSF professor and acting director of the Bakar Computational Health Sciences Institute,* Dr. Chirag Patel, associate professor at Harvard’s Department of Biomedical Informatics,* Dr. Mike Snyder, chair of genetics at Stanford and longtime collaborator.Together, they reflect on Atul’s energy, his fearlessness, and his talent for getting to the right question. “Nearly everything I know about doing science I learned from Atul,” says Marina. “He taught us how to ask the right questions—and how to tell the story so others would care.”Chirag speaks to the connective tissue of Atul’s thinking: “He helped us link previously disconnected fields—gene expression, hospital systems, exposures—and showed us that the real frontier is in the integration.”Mike recalls Atul’s blunt honesty and unmatched creative force: “He was a fire hydrant of ideas. When others were cautious, he just said it like it was. And often, he was right.”The episode traces Atul’s influence from his early work mining public gene expression data at Stanford, to building the UCSF clinical data warehouse and leading data-sharing efforts across the entire University of California system. In each role, he remained committed to one core belief: that data should not sit idle—it should lead to insights, tools, and ultimately, better health for patients.From early exposomics to the new AI-enhanced diagnostics, his legacy stretches across the most urgent frontiers in biomedical research today. As Mike puts it, “There were no boundaries in Atul’s science. He just moved—quickly—into what mattered.” This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comMost cancer biomarkers aren’t found in your DNA—they’re found on a microscope slide. And according to Dr. Andy Beck, CEO and co-founder of PathAI, that slide is undergoing a digital transformation.In this episode, Andy takes us behind the scenes of modern pathology to reveal how AI is reshaping not only cancer diagnostics but also drug development. From…

In this episode of Mendelspod, we’re joined by Raju Rayavarapu, bioinformatician at DNAnexus and former FDA data specialist, to discuss how regulatory science is adapting to the age of AI, big data, and cloud platforms.* 0:00 How has AI changed regulatory informatics?* 4:15 KISS* 12:50 On standards* 25:00 So nothing new about AI? The juicy question of the interview* 32:45 Raju’s life: good days and bad nightsDespite the buzz around AI, Raju insists the fundamentals haven’t changed much. “It still essentially follows the same patterns,” he says. “Here's data that needs to be analyzed in order to help make a safety and efficacy decision.” What has changed is scale: more data, more submissions, more complexity. But also more tools.On that note, Raju makes a strong case for keeping it simple. “It's a really strange choice to do something like a complex language model when all you really need is a string search,” he says. Simpler tools not only reduce costs and computing overhead, they’re more transparent—an essential trait in a regulatory environment where explainability is everything.Oh, come on, Raju . . . what’s really different about AI? He warns against blind trust in black-box models, especially when trained on biased datasets. We also explore cloud adoption, standardization, and the global regulatory landscape. Raju explains how DNAnexus is working behind the scenes with agencies around the world to implement trusted environments and validate evolving standards. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe

This is a free preview of a paid episode. To hear more, visit www.mendelspod.com“Genomics works. Don’t be scared of it.” That’s the message from Mike Kreitzinger, a longtime Illumina leader now advising the Institute for Pediatric Rare Disease at Florida State University and stepping into a broader role as a genomics advocate.In this episode, Mike gives us an inside look at Florida’s newly funded Sunshine Genetics Act, which includ…

Illumina’s new interpretation software, Illumina Connected Insights, signals a turning point in oncology genomics—where sequencing power meets end-to-end clinical utility. On this episode of Mendelspod, host Theral Timpson sits down with Jing Gao, VP of Software Engineering at Illumina, to explore how the company is extending its leadership from sequencers to software.“We’ve moved from offering modular tools to building full-stack solutions,” Jing explains. “Connected Insights is about taking raw genomic data and delivering meaningful answers—quickly and consistently.”* 0:00 With Connected Insights, Illumina now has end-to-end support* 4:30 What’s your niche in oncology?* 10:40 Can software really interpret biology?* 14:45 What’s new and updated?* 17:00 The future of genomic interpretation in oncologyFrom variant annotation to case summaries aligned with clinical guidelines, Connected Insights integrates more than 55 curated databases, AI-driven tools like SpliceAI and PrimateAI-3D, and a design philosophy that emphasizes both comprehensiveness and human-centered transparency.Gao previews upcoming innovations—such as integration with Illumina’s MRD and Constellation technologies—and paints a future where interpretation is more automated, collaborative, and expansive.“Our goal,” says Gao, “is not to replace scientists, but to scale their expertise. Connected Insights is an intelligent assistant that amplifies what experts do best.”🎧 Also, don’t miss the GenomeWeb Webinar on July 9 at 10 AM EDT, where Jing Gao and team go deeper into real-world use cases and the future of variant interpretation in precision oncology. This is a public episode. If you'd like to discuss this with other subscribers or get access to bonus episodes, visit www.mendelspod.com/subscribe