Mendelspod Podcast

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

Christian Henry, CEO of Pacific Biosciences, discusses the pivotal role of DNA in genomics and the anticipated launch of the Vega system, a groundbreaking long-read sequencer priced at $169,000. He highlights how this innovation enhances access to long-read sequencing and addresses the pressing concerns over NIH funding and its potential impact on research. Henry is optimistic about the future of genomics, emphasizing the unique discoveries that long reads unlock, including those in epigenetics and disease understanding.

This is a free preview of a paid episode. To hear more, visit www.mendelspod.comIt’s time for our annual deep dive into sequencing—no, wait—multi-omics! Back on the show is our resident sequencing guru, Keith Robison, scientist at Ginkgo Bioworks and author of the OmicsOmics blog. Keith is our all time return champion, and as always, he brings technical experience alongside the storytelling instincts of a seasoned journalist.Keith …

This week on Mendelspod, as we celebrate International Women’s Day, we’re spotlighting groundbreaking contributions from women in science. Our guest, Dr. Mirna Ghemrawi, is at the forefront of forensic genetics, where DNA analysis meets the pursuit of justice. As Associate Director at the Center for Forensic Science Research and Education, Ghemrawi applies next-gen sequencing and AI to some of the most challenging questions in forensic biology.Originally from Lebanon, Ghemrawi’s path to forensic science began in the medical field before she earned a Fulbright scholarship to study in the U.S. and ultimately pursued a PhD in forensic genetics. “I always knew I had a passion for forensics,” she says. “There weren’t many opportunities back home, but I knew that any science-related field would help me get there.”One of the most exciting areas of her current research involves using genetic and epigenetic markers to predict what a suspect may look like—an approach that, when combined with forensic genetic genealogy, could revolutionize investigations. “The idea is that we can not only get human identification from DNA but also predict age, eye color, hair color, and even certain phenotypic traits,” she explains. “If this works, it could help narrow down family trees in genealogical investigations.”The conversation also touched on the evolving challenges in forensic science, particularly as DNA analysis becomes more sensitive. Questions around DNA transfer—whether genetic material was directly or indirectly placed at a crime scene—are increasingly shaping legal arguments. “We can now get a profile from an incredibly small sample,” Ghemrawi notes, “but that raises questions about how the DNA got there, and courts are having to consider these new complexities.”Ghemrawi is passionate about mentoring the next generation, particularly encouraging young women to step into forensic science. “The only way you know you can’t do something is by trying,” she advises. “Ask questions, be persistent, and don’t be afraid to push into new territory.” 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 urgent and unflinching conversation, Stanford law professor Hank Greely returns to Mendelspod to address the mounting threats of the Trump administration to public science funding and the institutions that regulate medicine. As the NIH faces existential challenges and the FDA comes under fire, Greely lays out a compelling case for why government-supported research remains essential—not just for innovation, but for maintaining a functional society.“Research is like fishing,” Greely explains. “You cast your net, and sometimes you catch something big, sometimes you don’t. But if you stop casting altogether, you’re guaranteed to catch nothing.” He argues that long-term investment in science is the only way to sustain real progress, even if individual studies don’t always yield immediate breakthroughs.Greely also draws a stark historical comparison, warning that the current climate resembles the Communist Cultural Revolution, “except this time the war on expertise and knowledge isn’t coming just from the top down—it’s being fed from every direction.” The consequences, he suggests, could be felt for generations.Yet, while calling for outspokenness, Greely also urges compassion for those in academia and government who feel they cannot safely speak out. “Some of the people who aren’t being as forthright as we’d like—it’s not personal cowardice,” he says. “They’re trying to protect their institutions, their labs, their students, their colleagues. And that’s something we need to understand, even as we push for change.” 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