Mendelspod Podcast

Theral Timpson

Offering a front row seat to the Century of Biology, veteran podcast host Theral Timpson interviews the who's who in genomics and genomic medicine. www.mendelspod.com

  1. Building the Diagnostic Layer of Modern Cancer Care with Rita Shaknovich and Karina Kulangara of Agilent

    May 29

    Building the Diagnostic Layer of Modern Cancer Care with Rita Shaknovich and Karina Kulangara of Agilent

    For years, precision oncology has largely been discussed through the lens of breakthrough drugs. But there’s another story running underneath modern cancer care: the quiet rise of companion diagnostics. These tests are increasingly deciding who receives those therapies in the first place. In many cases, the real bottleneck is no longer discovering a drug target. It’s building a reliable system for identifying the right patient at the right moment in the disease. That challenge sits at the center of this conversation with Rita Shaknovich, Chief Medical Officer for Life Sciences and Diagnostis, and Karina Kulangara, Associate Vice President of R&D in Companion Diagnostics at Agilent Technologies. Agilent has always had a major role in this field. Rita and Karina explain how companion diagnostics evolved from the original Herceptin test into a vision for a much broader ecosystem spanning pathology, automation, regulation, and global clinical deployment. We dive into Agilent’s recent FDA approval expanding PD-L1 IHC 22C3 PharmDx into ovarian cancer, a development both guests describe as particularly meaningful given the historically poor outcomes associated with the disease. As Rita puts it: “Precision medicine is based fundamentally on scientific truth . . . it brought real results for patients. It brings better survival for patients, fewer side effects from the medication.” Karina offers one of the clearest explanations we’ve heard for why immunohistochemistry or IHC has endured so long in modern oncology. “It’s the ability to detect protein biomarker in the spatial context of the tissue,” she explains, emphasizing that location and cellular context can fundamentally shape how therapies work. What emerges is a picture of precision oncology that is becoming less exotic and more routine. We’re talking not just new drugs, but an entire clinical and technological infrastructure which is designed to match therapies to biology more effectively and over time. 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

    32 min
  2. Mapping the Multi-Omic Era with Eric Green of Illumina

    May 28

    Mapping the Multi-Omic Era with Eric Green of Illumina

    Dr. Eric Green returns to Mendelspod in a new role: Chief Medical Officer of Illumina. After more than three decades at the National Human Genome Research Institute, where he helped guide genomics from research initiatives to clinical reality, he now joins one of the industry’s most influential companies at a moment when the field is expanding beyond DNA alone. Green takes us on a tour around the world of multi-omics, which he says is not a branding exercise but a practical response to the limits of sequence data by itself. Genomics remains foundational, but many clinical questions require additional layers of biology, including RNA, epigenomics, proteomics, and single-cell analysis. As he puts it, “DNA sequence alone may not reveal it.” The discussion highlights rare disease as one of the clearest examples. Genome sequencing can solve roughly half of suspected cases, Green notes, but many patients remain undiagnosed because the relevant signal may lie in RNA splicing, epigenetic regulation, structural variation, or downstream protein effects. In those settings, multi-omic approaches can provide the missing evidence needed to move from uncertainty to diagnosis. In oncology, the challenge is different. Cancer genomes can be highly complex and heterogeneous, making it difficult to distinguish driver events from background noise. That is one reason why researchers and clinicians are increasingly incorporating methylation markers, transcriptomic data, and proteomic signals into early detection, disease sub typing, and monitoring strategies. Green also emphasizes that the next bottleneck may be less about generating data than interpreting it. “The human brain is not going to be the thing that’s going to crack this nut,” he says. “It’s going to be AI and computational biology.” The result is an overall picture of where the field may be headed as we go from genomic medicine to a broader molecular medicine with multiple data types that will improve diagnosis, stratify disease, and guide care worldwide. 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

    44 min
  3. Separating Epigenetic Signals Improves Early Cancer Detection with Rob Osborne, Biomodal

    May 19

    Separating Epigenetic Signals Improves Early Cancer Detection with Rob Osborne, Biomodal

    We’ve gotten very good at reading DNA. We’re just beginning to understand how to read its state. On today’s show, Rob Osborne, Senior Vice President of R&D at Biomodal, discusses new evidence that separating two epigenetic marks—5-methylcytosine and 5-hydroxymethylcytosine—can improve early cancer detection from liquid biopsy. In a recent Nature Communications Medicine study, his team showed that analyzing these signals independently in circulating DNA significantly enhanced detection of Stage I colorectal cancer compared with approaches that combine them. The advance does not require new sequencing hardware. Biomodal’s approach uses a sample preparation kit compatible with existing platforms, paired with bioinformatics tools, potentially lowering the barrier to adoption while expanding the information content of standard sequencing workflows. The underlying insight is biological as much as technical. Most methylation assays collapse 5mC and 5hmC into a single signal, masking early transitions in gene regulation. Osborne describes this as “squishing them into one output,” a simplification that can obscure meaningful changes in disease onset and progression. By separating the signals, the study identified patterns that emerge earlier in tumor development, offering a more sensitive window into disease biology. But the deeper message of the interview is that this work may only scratch the surface. “I think that we’re just at the beginnings of really understanding this biology,” Osborne 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

    23 min
  4. Solexa Co-Inventor Shankar Balasubramanian on Six-Base Sequencing and What's Next in Genomics

    May 7

    Solexa Co-Inventor Shankar Balasubramanian on Six-Base Sequencing and What's Next in Genomics

    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

    38 min
  5. The Next Frontier in Biology: Physics? Erdinc Sezgin of the Karolinska Institute

    Apr 30

    The Next Frontier in Biology: Physics? Erdinc Sezgin of the Karolinska Institute

    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

    33 min
  6. The Case for a 6-Base Genome with Peter Fromen, CEO of Biomodal

    Apr 28

    The Case for a 6-Base Genome with Peter Fromen, CEO of Biomodal

    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 clinic In 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

    35 min

Ratings & Reviews

4.6
out of 5
34 Ratings

About

Offering a front row seat to the Century of Biology, veteran podcast host Theral Timpson interviews the who's who in genomics and genomic medicine. www.mendelspod.com

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