Mendelspod Podcast

“We have been talking now for 15, 20 years about the diagnostic odyssey. That shouldn’t exist anymore. The new odyssey is the therapeutic odyssey.”
That’s Stephen Kingsmore, president and CEO of Rady Children’s Hospital (he just announced his retirement), explaining the impact of a new genome mapping technology from Illumina.
Whole-genome sequencing has transformed diagnosis, but some of the hardest pediatric cases persist because the structure of the genome has remained difficult to resolve. Today on Mendelspod, we cover Illumina’s newly launched proximity mapped reads, showing how long-range genomic context can be captured directly on existing Illumina sequencers and integrated into the lab workflow. The conversation traces how this added structural clarity is already improving diagnostic confidence and, critically, enabling highly precise n-of-1 therapies such as antisense oligonucleotides (ASOs).
Olivia Kim-MacManus, a pediatric neurologist and ASO trial leader, shows how the new diagnostic precision directly feeds therapeutic design.
“All of these genetic therapy approaches hinge on precise diagnostics,” she notes, emphasizing that allele-specific and haplotype-aware targeting is essential for ASOs and other emerging gene-based interventions.
From the product and workflow side, Ali Crawford joins us as Senior Director of Science Research at Illumina, detailing how the technology works without requiring new instruments or complex workflows, eliminating the need for separate library preparation steps.
“You just order the kit and go,” she says, highlighting how preserving spatial information on the flow cell unlocks variant calls and structural insight that were previously inaccessible with their standard short-read sequencing.
When genome structure comes into better focus, treatments are no longer theoretical.


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

CareDx is a company on the move. For years, they have been a bellwether in molecular diagnostics. Their early bet on gene expression testing in transplant medicine, their bruising fight over Medicare coverage, and their pivot into cell-free DNA monitoring have all reflected the growing pains of precision medicine itself.
Now, under CEO John Hanna, the company looks less like a single-test diagnostics firm and more like a clinical ecosystem.
Hanna brings an unusual vantage point. He began his career in health insurance before moving into molecular diagnostics—giving him insight into both innovation and reimbursement. That dual perspective shaped CareDx’s recent evolution: focus tightly on a defined clinical niche—transplantation—while expanding horizontally into the tools, software, and services that surround it.
Today, CareDx operates across three segments: lab products (including high-resolution HLA typing kits using PCR, NGS, and nanopore), a growing software and patient solutions business, and its flagship genomics portfolio led by AlloSure, its donor-derived cell-free DNA assay. What distinguishes the company now is its “solution selling” approach—engaging transplant centers not just with a test, but with workflow software, quality reporting tools, specialty pharmacy, and EMR integration.
“Our solution selling strategy is working,” he says today.
At the scientific core remains the effort to replace invasive biopsies with molecular monitoring. AlloSure’s innovation—detecting donor-derived cell-free DNA without requiring donor genotyping—made routine blood-based rejection monitoring scalable. Yet adoption is not purely technical.
“The biggest challenge with our space is building belief that molecular testing can replace tissue biopsy.”
Clinician education, clinical trials, and guideline inclusion remain central to shifting standards of care. CareDx has leaned heavily into this, hiring medical leadership specifically to translate data into practice. The company is also layering AI on top of its molecular assays. AlloSure Plus integrates genomic results with EMR-derived clinical variables to generate a rejection risk score. CareDx’s operational mantra has been to put the burden of complexity on the company, not the clinician.

Large-scale genomics is back — and this time, it’s global by design.
In this episode of Mendelspod, we return to the kind of ambitious, shared genomics project that helped define the field a decade ago. The Global Parkinson’s Genetics Program (GP2) has now genotyped more than 100,000 participants worldwide, with roughly one third of samples coming from historically underrepresented populations. That scale and diversity are already reshaping how Parkinson’s disease is studied — and how it may eventually be treated.
My guests are Andrew Singleton, co-lead of GP2, and Ignacio (Nacho) Mata, a geneticist at Cleveland Clinic and founder of the Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD). Together, they describe how globally representative datasets are not a political aspiration, but a scientific necessity — especially in an era of precision medicine.
Singleton explains that studying Parkinson’s across populations doesn’t just broaden participation; it increases scientific power.
“The more we learn about individual populations, the more we understand about disease as a whole — and the more chances we have to come up with treatments for disease as a whole,” he says.
Mata brings a complementary perspective from years of building Parkinson’s genetics infrastructure in Latin America. He emphasizes that without inclusion in genetic and biomarker research, entire populations risk being excluded from the next generation of molecularly targeted therapies.
“If we don’t have our patients studied for genetics or biomarkers, then those patients will not have access to the new treatments,” he notes, adding that GP2 is designed to narrow rather than widen existing health disparities.
We explores how GP2’s open-science structure has been key to its success and could serve as a model for other global research projects. GP2 has invested heavily in training and infrastructure so that researchers around the world can lead analyses locally, rather than simply contributing samples.
As both guests make clear, this is only the beginning. With hundreds of thousands of samples committed and a new generation of globally distributed investigators, GP2 is laying the groundwork for biologically defined subtypes of Parkinson’s and for more precise diagnostics and disease-modifying therapies.
When genomics gets big enough — and inclusive enough — scale itself becomes a discovery.


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

What if the hardest part of scaling cell therapy turned out to be a materials problem not a biological one—and the solution looked like a sponge?
On today’s show, Theral speaks with Yev Brudno, Associate Professor in the School of Pharmacy and also the Department of Biomedical Engineering at the University of North Carolina at Chapel Hill, about a deceptively simple technology that could dramatically accelerate manufacturing and lower the cost of cell therapies. Brudno’s lab works at the intersection of chemistry, biomaterials, and cell biology, with a focus on removing the manufacturing and scalability barriers that have kept powerful therapies like CAR-T out of reach for most patients.
At the center of the conversation is a dry, porous biomaterial sponge—developed initially by accident—that boosts viral transduction efficiency from roughly 10% to as high as 90% by forcing cells and viral vectors into intense, highly efficient contact. The sponge works across multiple delivery systems, including retroviruses, lentiviruses, AAVs, and even lipid nanoparticles, effectively functioning as a low-cost, scalable alternative to complex microfluidic systems. Brudno explains how this discovery reframes genetic modification as a physical- and materials-science problem rather than a purely biological one.
The discussion goes beyond mechanism into real-world impact. Brudno describes how these sponges—now commercialized for research use by Takara Bio USA—could compress weeks-long CAR-T manufacturing workflows into hours, enabling bedside or community-hospital cell engineering without the need for $100-million cleanroom facilities. The episode closes with a broader reflection on the future of cell therapy.
Once again, some of the most transformative advances might come from curious bench science and happy accidents rather than prediction alone.


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

For today’s show, we return to discussing the exciting new Cellanome platform. Joining Theral are Pier Federico Gherardini, VP of Computational Biology at Cellanome, and Matthew Spitzer, Associate Professor at University of California, San Francisco, whose lab is using Cellanome’s CellCage technology to study immune cells in dynamic, interactive contexts.
0:00 From static snapshots to observing cell function in real time
4:45 Pairing phenotype with function like we never could before
7:30 Can see cell-cell interaction
19:40 Early applications
Rather than relying on static single-cell snapshots, the Cellanome platform enables longitudinal observation of live cells—tracking division, interaction, and function over time—before pairing those behaviors with transcriptomic and molecular readouts. As Gherardini explains, “This creates essentially a new data type where you observe cells over time… and then you can pair all of that functional information with the molecular readouts that you get from sequencing.”
For Spitzer, that shift fundamentally changes what can be known. Traditional approaches often force scientists to infer function indirectly, correlating phenotype measured in one experiment with behavior measured in another. With CellCage, his lab can finally measure both in the same individual cell.
“Now we have measured the function of the cell and the phenotype for the same exact individual cell,” Spitzer says, “and this allows us to really understand how those core characteristics are linked in a much more detailed way.”
For Spitzer, a major advance comes from observing cell–cell interactions as they unfold. Where previous methods could show proximity in a tissue section, they could not reveal outcomes. Using Cellanome, Spitzer’s team can now watch whether a T cell activated by a dendritic cell actually proliferates, produces effector molecules, or kills a tumor cell—and then trace those outcomes back to specific molecular programs. This has already revealed surprising heterogeneity within supposedly uniform cell populations, identifying rare but highly potent immune cells that would have been invisible in bulk assays.
Looking ahead, both guests see immediate applications in cell therapy development, target discovery, and functional CRISPR screening—areas where measuring what cells actually do matters more than what they merely express. We close with a sense that cell biology is entering a new phase—one where function, interaction, and time are no longer inferred, but directly observed, measured, and modeled.


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