Mendelspod Podcast

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?


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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.


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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 is
A 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.



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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 biology
Across 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.



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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 heading
This 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.


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