Mendelspod Podcast

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,…

What if you could step inside a molecule? On today’s episode of Mendelspod, we talk with Steve McCloskey, founder and CEO of Nanome, the company bringing virtual reality into the world of drug discovery and molecular modeling. A former nanoengineering student at UC San Diego and a self-described futurist, Steve founded Nanome to create what he calls the "ultimate scientific interface"—a way for scientists not just to visualize molecules, but to interact with them naturally in 3D space.* 0:00 The ultimate science app* 2:15 A use case* 7:15 How does VR interaction change things?* 12:47 Intuition at the nanoscale * 23:10 Can VR redefine biological models and become the norm?* 35:15 Hard to give career advice now with rapid rise of techNanome’s VR platform enables researchers to grab, rotate, and manipulate proteins, explore molecular dynamics, and even collaborate remotely inside a shared molecular environment. Built with both scientific rigor and the playful spirit of a 3D gamer, Nanome is already being used from classrooms to major pharmaceutical firms.One of the most compelling ideas discussed today is the possibility that VR can help biologists build intuition at the nanoscale, much like space exploration and science fiction helped earlier generations develop intuition about the cosmos. "Ninety-nine percent of people have no intuition for the nanoscale," McCloskey says. "You look at molecules on a 2D screen, and it's like a ball of spaghetti. But in VR, you pretty much instantaneously get it."​This new kind of "nano-intuition" could, McCloskey argues, open doors for faster discovery, better communication, and broader scientific literacy. As he puts it, "Space is fascinating because it's so vast and mysterious. But the nanoscale is even denser with phenomena—and we’re just beginning to explore it."​Looking ahead, Steve sees VR as becoming a normal part of the scientific workflow. Though today's headsets are still bulky, future versions could be as light as eyeglasses, embedding a whole new layer of spatial computing into everyday research.As Steve says: "If we can give scientists—and even the general public—intuition for the nanoscale, it might radically change how we approach biology, drug development, and science education 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

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comWait! What? Sequencing as a service?That was the reaction when Mark Budde first set out to upend a basic ritual in molecular biology—confirmation Sanger sequencing—with his company Plasmidsaurus. You’ve heard it many times: Illumina machines sequence around 80% of the bases in the world. But as Mark points out in today’s interview, it’s not 80% of th…

Just weeks before the FDA’s sweeping rule to regulate laboratory-developed tests (LDTs) was set to take effect, a federal court struck it down. What does this mean for the field of precision medicine and for labs themselves? There are have been those on the side of regulation arguing its importance for reimbursement. Yet many, such as the plaintiffs in this case, the ACLA and AMP, have argued that FDA regulation could stifle innovation in a new field and even force labs to shut down. Today we talk with Sarah Overton, Senior Director of Revenue Cycle Management at Velsera, whose team helps clinical labs with everything from validation to reimbursement strategy. She walks us through the practical implications of the ruling. “It came just in time. Even meeting stage one was going to be incredibly burdensome,” she says in today’s interview. (Link to a webinar with Sarah on this topic here.)* 0:00 Impact of recent court decision on LDTs * 5:15 Supports an in-between regulation * 15:15 How are your clients choosing between LDT and IVD?* 20:00 Topic goes hand-in-hand with reimbursement * 25:20 Every test is differentInstead of scrapping oversight altogether, Overton argues for a middle ground — more robust than the current CLIA framework, but less rigid than the FDA’s approach. “We need something in between,” she says. “There are already mechanisms in place — like MolDX’s technical assessment — that address analytic validity, clinical validity, and clinical utility. That could be a model to build on.”We explore how Velsera’s clients are choosing between launching LDTs or IVDs, and what factors drive that decision. Overton emphasizes that reimbursement strategy must be integrated from the beginning — not bolted on at the end. “The test might be clinically excellent, but if it’s not reimbursable, it won’t sustain a lab,” she warns.“We need standards that ensure quality without crushing innovation,” she says. “There are ways to do that now. Let’s build on what’s working.” 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 today’s show, Theral is joined by Chris Petersen, Chief Technology Officer at Scientist.com, a company sometimes called the "Amazon for science"—though with a great deal more complexity. Chris pulls back the curtain on how AI is transforming the research services marketplace and offers a rare look into how AI is already reshaping the infrastructure of pharma and biotech.Calling this the "tinkering phase" of AI, Chris likens the current moment to the early days of the web—when best practices were still forming and every developer had to invent their own solutions. “It’s one of the most exciting times to be a software developer,” he says, describing how AI has enabled a leap forward in productivity across the board—from writing code to streamlining negotiations and customer service. One internal tool, Elisa, functions like a fine-tuned ChatGPT within Slack, answering employee and customer queries on the fly.AI, he says, is speeding up nearly every part of the business. "There are all of these problems that were impossible to solve a year and a half ago. And now you can solve them. One of the hardest things… is your old preconceptions of what you're capable of? You have to let some of that go because you're capable of so much more now."Petersen also talks risk: while AI promises a democratizing effect, making outsourcing more accessible to small players, he warns of the dangers of consolidation—where just a few massive models hold everyone’s data. To avoid that future, Scientist.com is building its own internal LLMs, training and fine-tuning models like Mistral and DeepSeek on proprietary data, all under an evolving platform they call Benchmate.Scientist is betting that AI will not only enhance their marketplace but change how science itself is organized and conducted. Stay tuned for more in this new series on AI. 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 today’s program, we continue our series on disease subtyping with Dr. Jeffery Klco, a pediatric pathologist and researcher at St. Jude Children’s Research Hospital. Dr. Klco joins us to discuss groundbreaking work recently published in Nature Genetics, which redefines the genomic landscape of childhood acute myeloid leukemia (AML).Klco and his team have identified twelve novel molecular subtypes of pediatric AML—some driven by genetic alterations that had long gone undetected by standard computational tools. Chief among these is the UBTF tandem duplication, a complex mutation previously overlooked but now shown to be a distinct disease subtype that accounts for up to 10% of pediatric AML cases and is associated with relapse and poor outcomes.“We’ve been misclassifying childhood AML for years,” says Klco. “It’s the same disease as in adults—but it behaves very differently. And we’ve been using an adult framework to treat kids.”* 0:00 We’ve been misclassifying childhood AML* 7:25 Challenges with current treatment paradigm* 11:05 Doing clinical whole genome and RNA sequencing* 17:25 How might this new approach work for other pediatric cancers?The conversation delves into how St. Jude’s use of whole genome and RNA sequencing, paired with advanced analytics, has enabled more precise subtyping. In response, Klco’s team is already developing targeted therapies, including the use of menin inhibitors, which have shown early promise.But discovery is just one side of the coin. Implementation is another. Klco discusses the development of a new 357-gene panel—specifically designed for pediatric cancers and incorporating structural variants—that is now in clinical use at St. Jude. It fills key gaps in diagnosis, risk stratification, and minimal residual disease monitoring, especially in complex cases such as post-transplant patients or those whose tissue samples are incompatible with full genome sequencing.Asked about future potential, Klco notes that while most pediatric cancers may now be genomically defined, new methods such as long-read sequencing and methylation profiling still hold promise for sharpening diagnostic tools and stratifying risk.“Pediatric cancers are driven by different genomic forces than adult cancers,” he explains. “Even within the first 18 years of life, we see distinct subtypes emerge at different ages. If a child under three comes in with AML, I already have a good idea what subtype it might be.”It’s a compelling example of how detailed genomic subtyping is not only advancing our understanding of pediatric disease—but directly shaping the next generation of therapies. 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

Dr. Aaron Viny, oncologist and researcher at Columbia University, begins today’s conversation with a personal milestone—he’s now been leukemia-free for 21 years. This experience gives his work on cancer a powerful human dimension that comes through in his interview with Theral today—not only in his dedication to patient care, but in his boundary-pushing research on the epigenetic roots of cancer.Dr. Viny’s research focuses on the epigenetic architecture of hematologic malignancies, exploring how errors in chromatin structure—not just mutations in DNA—can lead to cancer. “Cancer, at its root, is often a disease of dysregulated identity,” he says. “Cells that have lost their ability to regulate their own gene expression are primed for malignant transformation.” This breakdown in regulation becomes a doorway to cancer—a perspective that reshapes how we think about both origin and treatment.* Chapters:* 0:00 Leukemia free for 21 years* 5:25 Life as a researcher at Columbia University today* 8:30 Epigenetics and cancer etiology* 17:03 Impact of new spatial and single cell tech* 25:00 What is hypomethylating treatment?* 28:40 Using type and proximity of cell surface proteins to understand immune regulation* 34:15 What next?Dr. Viny discusses how emerging spatial and single-cell technologies are giving researchers a new kind of lens into these processes. The tools allow him and others to study not just what genes are expressed, but where in the tissue and in what context—something that’s proving crucial for understanding the complexity of the tumor microenvironment. He highlights the use of Pixelgen's platform for analyzing cell surface proteins, which offers fine-grained insights into how immune cells interact with cancer cells. “The type and proximity of cell surface proteins,” he notes, “tell us an entirely new story about immune regulation.”He also speaks candidly about the realities of doing science today, especially within a strained academic system. Despite recent threats to research funding at Columbia, Dr. Viny remains resolute: “If we’re not investing in understanding cancer, what are we doing?” 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 happy to welcome back Ben Busby, Principal Scientist at DNAnexus, to dive deeper into the evolving world of disease subtyping and multi-omic data sets. Building on our previous conversation with Busby about the genomic data ecosystem, we explore the shift from single-cause disease models to multifaceted approaches that incorporate genomics, proteomics, imaging, and more."We’re no longer in a world where we’re doing genomics or imaging or proteomics," he explains. "These things are all coming together, and it’s important that they do. The UK Biobank will soon have 80 million images."Busby highlights the UK Biobank’s leading role in this transformation, with its extensive genomic, imaging, and clinical data available to researchers worldwide. He emphasizes the importance of enabling scientists to access and analyze vast datasets collaboratively while ensuring participant privacy, and points to the role of DNAnexus in providing a trusted research environment where multiple stakeholders, from pharma to academia, can work with data efficiently and securely.The episode also explores the impact of AI in bioinformatics, particularly in hypothesis generation. "AI is helping us think beyond single-cause events," Busby notes, referencing its ability to generate novel insights from complex biological data. He underscores the need for proper alignment between AI systems and scientific goals, stressing that human intuition remains essential in guiding these technologies toward meaningful discoveries.As the field moves forward, Busby calls for more equitable data sharing practices, ensuring credit for data generators and benefits for study participants. "We need to figure out how to incentivize data generation in a way that’s fair and equitable," 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

John Cumbers, founder of SynBioBeta, is a pioneer in synthetic biology and AI integration. He discusses the blending of these fields, emphasizing its potential to transform our understanding and engineering of biology. Cumbers highlights the need for a 'ChatGPT moment' in synthetic biology to enhance public engagement and awareness. He explores themes for the upcoming SynBioBeta 2025 conference, including advancements in longevity, AI-driven drug development, and innovative applications of non-canonical amino acids—all crucial for making biology more accessible.

Today Theral is joined by returning guests Chris Mason of Weill Cornell Medicine and Simon Fredriksson, CEO of Pixelgen Technologies, for a deep dive into the emerging field of cell surface proteomics and its power to illuminate both space biology and cancer research.Chris Mason shares new insights from his work on the Space Omics and Medical Atlas (SOMA), the largest collection of astronaut health data to date. His latest findings confirm that space is more than a hostile environment—it’s a revealing one. Space is a kind of alternate reality that lets us test fundamental questions about biology and human health. Mason says changes in telomere length, immune system behavior, and skin inflammation during spaceflight are offering a new window into how the body responds to stress—whether in orbit or in disease states like cancer on Earth.Enter Pixelgen’s breakthrough technology, the proximity network assay, which allows researchers to map how proteins are organized on the surface of immune cells with nanoscale precision. As Fredriksson explains, “Cells don't operate only by parts lists, but by how they're organized to do all their functions.” Their approach enables the first large-scale spatial mapping of protein-protein interactions in three dimensions using DNA sequencing—unlocking insights not possible through traditional single-cell or bulk assays.In a collaborative effort, Mason’s lab and Pixelgen are applying this technology to study T-cell dynamics during spaceflight and in acute myeloid leukemia (AML). The results are striking: specific protein markers cluster together only during spaceflight and only at relapse in leukemia, offering clean, quantifiable signatures with clinical potential.As Mason puts it, “This is a new modality of data—it forces you to ask, ‘Well, what does this mean?’ And you’re like, ‘Well, we’ve never seen it before.’ So we’re figuring it out.” Whether predicting relapse in cancer or designing better drugs for space and Earth, cell surface proteomics is opening a new frontier in biomedical science. 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