Mendelspod Podcast

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

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comCan we finally replace animal testing in drug development—and still know a drug is safe and effective?That’s the provocative question at the heart of this episode, as we sit down with Andrei Georgescu, co-founder and CEO of Vivodyne. The company is developing robotic, AI-enabled systems for growing living, biopsy-like human tissues that can be used to t…

In this episode of Mendelspod, Theral welcomes Dr. Rita Shaknovich, Chief Medical Officer in Agilent’s Life Sciences and Diagnostics group, for a high-level and deeply insightful look at where liquid biopsy technology stands today.With her background in hematopathology and molecular diagnostics, Rita brings clarity to a field that has long promised transformation—and is now delivering. “It’s not the future anymore. It’s actually here,” she says. Liquid biopsy has moved beyond the buzzword phase and is increasingly integrated into both clinical trials and standard care for cancers like non-small cell lung cancer.We talk about why fluids are such a powerful source for diagnostics, with Rita reminding us, “Sixty percent of our body is water.” Sampling these accessible fluids not only makes for less invasive testing but also captures the heterogeneity and clonal evolution of diseases like cancer better than traditional biopsies.Rita also offers a tour through the latest technology advances, from target enrichment chemistry to the rise of multiomic platforms, including Agilent’s Avida portfolio. “There are 30 million CpG sites in the genome that can be methylated,” she explains, highlighting why DNA methylation is such a rich source of diagnostic information.She discusses the operational hurdles labs face in adopting liquid biopsy—chief among them being assay complexity and staffing—and how automation and customizable panels are easing the way.The show concludes with a call to action: "We are very slow often as a medical community adopting new tools. I hope we will democratize access as the clinical evidence grows.”Bonus: To go deeper, listeners are invited to attend a GenomeWeb webinar on July 8th, presented by Dr. Nicola Normanno, a leading voice in the liquid biopsy space. 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 episode of Mendelspod, Theral speaks with Frédéric Debode, Scientific Director at CRA-W in Wallonia, Belgium, about the evolving landscape of GMO detection in the age of gene editing. From early work in real-time PCR to the latest in next-gen sequencing and target enrichment, Debode has been on the front lines of tracking genetically modified organisms—often when the modifications leave almost no trace.What’s at stake? In Europe, labeling GMOs is not just a policy—it’s the law. Debode emphasizes that public trust hinges on scientific transparency: “Thanks to correct labeling, people can choose if they decide to eat or not food that is coming from GMOs.”* 0:00 What led you to GMO detection?* 4:00 How has your approach evolved?* 11:00 NGS plus target enrichment* 16:10 What are you testing?* 21:00 The future of GMO detectionThe conversation dives into the challenges posed by CRISPR and other new genomic techniques (NGTs), which can make single-base edits indistinguishable from natural mutations. “With CRISPR,” Debode explains, “you are not obliged to introduce a large fragment into the genome. You can just modify one base… and in fact, you will have a big effect.”Debode outlines how CRA-W is adapting its toolkit to these challenges, turning to high-throughput sequencing with target enrichment technology to screen for even subtle genetic changes. He also shares how Belgium and the EU are investing in collaborative efforts like the DETECTIVE project to establish viable detection protocols across a broad diversity of organisms.The work isn’t just regulatory. CRA-W is partnering with farmers and industry to improve diagnostics, ensure safety in bio-based fungicides, and support sustainability through gene mapping. “We’re not doing this alone,” says Debode. “There’s a strong European network working together to make these tools applicable and enforceable in the field.”For more from Debode on GMO detection, tune into an upcoming GenomeWeb 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

“We’re going to be rewriting the textbooks on how tissues work.”In this compelling reunion with spatial biology pioneer Joe Beechem and a first-time visit from Oliver Braubach, we explore the rapid evolution of spatial technologies at Bruker, a legacy instrumentation company newly resurgent in the spatial space. Following Bruker’s acquisition of Nanostring and Canopy, the company has emerged as a unifying platform where whole-transcriptome discovery meets translational assay development—under one roof.* 0:00 Red alert: we don’t yet understand how tissue biology works, and don’t let anyone tell you we do.* 5:12 Customer of spatial turned toolmaker* 10:00 What do you want researchers to know about Bruker Spatial?* 14:24 How do you go from discovery to assay?* 18:09 How has AI impacted spatial?* 22:41 The ongoing question of reductionism* 31:00 What’s your biggest challenge?Beechem, known for launching the first high-plex spatial platform at Nanostring, returns to Mendelspod to declare that spatial biology may be more consequential than genomics itself. “If somebody tells you they understand how tissue biology works, you can just cut them off. They don’t,” he says, describing the dramatic leaps from 84-plex in 2019 to 20,000-plex subcellular imaging today.Braubach, a neuroscientist turned toolmaker, shares his journey from early customer to R&D leader, developing user-friendly platforms that empower researchers with flexibility and speed. “We want researchers to assume again a degree of power over their assays,” he says, outlining Bruker Spatial’s mission to integrate discovery and translation.Together, the two leaders discuss how AI is accelerating the power of spatial, with foundational models that can identify patterns humans can’t. Beechem recounts feeding high-plex images into a GPT model: “It came back and told me where to look. And it was right.”They also reflect on the philosophical shift spatial enables—moving beyond genomics' reductionist lens toward a more holistic view of biology in situ. “The hype around spatial is not hype,” says Beechem. “It’s real.” 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.comIn this episode of Mendelspod, Theral sits down with Rob Neely, co-founder and CSO at Tagomics, to discuss how his company is fusing genomics, epigenomics, and fragmentomics into a single, assumption-free assay for early cancer detection. The conversation begins with breaking news: Tagomics has just received a new grant from the UK’s Innovation Agency a…

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comIn this premium episode of Mendelspod, we’re joined by one of the few people speaking clearly and globally about biosecurity in the era of synthetic biology and AI: Sophie Peresson.A consultant and leader in responsible innovation, Sophie brings an unusually broad and grounded perspective. With experience spanning international law and governance, she p…

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comAs artificial intelligence continues to influence the life sciences, some researchers are questioning not just what it can predict, but what it can explain. On this episode, Mike Kiebish, VP of Platform and Translational Sciences at BPGbio, discusses the company’s “biology-first” approach to drug discovery—one that begins not with models or literature, …

In this episode of Mendelspod, we plunge into the shape-shifting world of RNA with Dr. Gavin Knott, associate professor at Monash University and alum of Jennifer Doudna’s lab. Knott is part of a new generation of researchers setting structural biology ablaze with AI, decoding RNA-guided systems and expanding the CRISPR toolbox far beyond its original scope.Knott introduces the listener to RNA not just as code, but as living language. He discusses how AI now allows scientists to see molecules in 3D at the beginning of a project rather than years into it: “You can take that protein sequence, run it through something like AlphaFold, and there it is, looking at you.”* 0:00 RNA - the shapeshifting paradox of a molecule* 4:05 Using AI: here’s an idea—maybe we know enough about biology* 6:50 The ARC Institute, and that one paper* 9:05 Structural biology at everyone’s fingertips* 18:10 Why are gene therapy companies going so slow?* 23:40 The grammar of RNAWith infectious curiosity, Knott explains how protein design is entering an era of intent, not just discovery. “Maybe we understand enough about the rules of biology,” he posits, “that we can design the proteins we need.” He describes his lab’s twin tracks: mining microbial genomes for novel RNA-guided machines and using generative AI tools like RosettaFold and BindSpace to build bespoke editors of DNA and RNA.The conversation touches on emerging efforts to mitigate off-target effects in gene editing using AI, the data limitations holding back RNA-protein modeling, and a powerful metaphor comparing static protein images to photos of horses.Knott makes a striking point: “We’ve known the spelling of RNA for a while, but now we’re trying to learn its grammar.” This, he explains, means understanding not just RNA’s sequence but its shape, movement, and silent punctuation marks—an effort he sees as the next frontier. 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 decades, drug discovery has followed two main roads: small molecules that can slip into cells but often lack precision, and biologics that offer specificity but struggle with delivery and manufacturing. In this episode, Christian Schafmeister introduces us to a third path: spiroligomers—synthetic, fused-ring molecules designed to combine the best of…

What if drug design didn’t depend on pre-existing biological data? In this episode of Mendelspod, Theral sits down with Aridni Shah, co-founder and CEO of Immunito AI, a Bengaluru-based biotech startup reinventing how we develop antibody therapies. Shah and her team are using artificial intelligence to design antibodies from scratch, bypassing traditional animal-based and data-heavy methods. “We no longer need to rely on pre-existing data,” she explains. “We’ve gone to the fundamental atomic level and learned basic physics, chemistry, and maths—why do two proteins interact?”* 0:00 Discovering new antibodies without relying on biological processes* 4:45 The platform - a structure first approach* 10:00 The business model* 15:05 Bringing mathematics and physics to biology At the heart of Immunito’s innovation is a proprietary mathematical transformation that translates raw 3D structural data into rich, generative models capable of designing antibodies for even “undruggable” targets. It’s an ambitious approach to rational drug design that prioritizes data efficiency, leveraging physics-based complementarity rather than brute-force sequence matching. Still early in development, Immunito is already seeing promising lab results and aims to partner with pharma while building its own pipeline. “We should have signed a few multimillion-dollar multi-target deals,” Shah says of their goals over the next few years, “and be looking to progress towards IND.” This conversation opens a compelling window into how AI, when grounded in mathematical and physical intuition, may radically transform 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

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comYes, the Trump economy has been tough on life science tools—but according to today’s guest, the business model was failing us anyway. It’s time to go back to rethinking the basics.Today we’re joined by Stephane Budel, founding partner at DeciBio, one of the leading market research and consulting firms focused on life science tools and precision medicine…

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comOn today’s episode of Mendelspod, Theral sits down with Giovanna Prout, CEO of Scale Biosciences, to explore a how the company is achieving new orders of magnitude of scale in the single cell space."In the past, single cell was one cell per well—maybe 96 cells per experiment," Prout explains. "Now, with our Quantum Scale platform, we can scale from 85,…