Mendelspod Podcast

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We’ve become remarkably good at reading cancer cells. Spatial biology enabled us to read them in context. Today we discuss a new Nature study suggesting that the tumor microenvironment—the immune cells, stromal cells, and surrounding biology that often determines whether a therapy succeeds or fails—can be measured from a simple blood draw, or liquid biopsy.
To do that we’re joined by Dr. Vincent Miller, an oncologist and former founding Chief Medical Officer of Foundation Medicine, and Dr. Mirna Jarosz, CEO of LiquidCell Dx.
The work introduces a striking idea. Rather than focusing only on mutations inside tumor cells, it identifies recurring spatial ecosystems within tumors and then shows that their signatures can be recovered from plasma cell-free DNA using methylation patterns. The implication is that liquid biopsy may soon reveal not only what mutations a tumor carries, but how its surrounding biology is organized before treatment ever begins.
But wait. How can blood possibly contain information about spatial organization inside a tumor? That answer unfolds gradually on today’s show, making the final portion of the discussion particularly rewarding.
As Jarosz explains, “We’ve condensed spatial biology to really critical and recurring biological programs. And then we can measure those in blood. So now we have that spatial insight of the tumor microenvironment in a liquid biopsy.”
For Miller, the significance is ultimately clinical. “The tumor is almost like an organ,” he says. “The ability to understand how that organ is constructed and what structures are near one another and how they’re functioning... is really the underpinning” of why patients with seemingly similar cancers can have dramatically different responses to therapy.
If this approach continues to hold up in larger clinical studies, liquid biopsy may expand from reading the genetics of cancer to reading its ecosystem. This shift could improve immunotherapy selection, longitudinal monitoring, and our understanding of cancer biology itself.

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For the past decade, liquid biopsy has largely been defined by oncology. Tumors shed DNA carrying mutations and epigenetic changes which allows researchers to detect cancer and monitor response. With this physicians are increasingly able to guide treatment. But chronic diseases are different. There is no tumor. Biological signals are subtle and quite d…

The future of genomics has arrived in Abu Dhabi.
On today’s show, Dr. Mohamed Alameri of the UAE Department of Health and Albarah El-Khani of M42 describe one of the most ambitious precision medicine efforts underway anywhere in the world: the Emirati Genome Program, which has already sequenced more than 900,000 genomes and is rapidly integrating that data into everyday healthcare.
The UAE program is not only a large sequencing effort and database—soon to be made available for research anywhere—but a coordinated national strategy built on prevention, diagnosis, and long-term population health. Particularly striking is the UAE’s focus on inherited and autosomal recessive diseases, which occur at significantly higher prevalence in the region than in many Western populations. Rather than treating genomics as an isolated research exercise, the program has pushed aggressively into premarital screening, newborn genomic screening, pharmacogenomics, hereditary cancer risk assessment, and rare disease diagnosis.
“We truly believe in the philosophy of ‘sequence once, analyze for life,’” says El-Khani. “Imagine a society where every individual from birth holds a whole genome sequence throughout their life. How powerful is that tool at every intersection of public health, clinical care, and screening?”
The scale of the project is already yielding discoveries difficult to achieve elsewhere. According to Alameri, roughly 12% of the variants identified in the Emirati population are not represented in existing global databases, underscoring just how underrepresented Middle Eastern populations remain in genomics research. In some cases, variants previously considered pathogenic in European populations appear to behave differently in Emirati patients, opening entirely new biological questions.
Perhaps the most impressive aspect of the program is the degree to which genomics has been operationalized across the healthcare system. The UAE has invested heavily in physician education and public engagement to move genomics from bench to bedside. Our guests describe a healthcare ecosystem where genomic reports, pharmacogenomic guidance, and hereditary risk assessments are increasingly available directly within clinical workflows.
“The vision was not sequencing everyone for its own sake,” says Dr. Alameri. “It was to build a national asset that could support more predictive, preventative, personalized healthcare for our population and for future generations.”
There is always hype in genomics, as with other emerging technologies. But the UAE effort is already very comprehensive and clinically grounded. This is genomics functioning as healthcare infrastructure in real time.


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On today’s show, Dr. Ryan Flynn of Harvard Medical School and Boston Children’s Hospital takes us into a newly emerging layer of biology: the architecture of the cell surface itself. Flynn first gained attention for the discovery of glycoRNA — RNA molecules displayed on the outside of cells — a finding that challenged the traditional picture of the cell surface as a world composed primarily of proteins and glycans. RNA has long been understood mainly as a carrier of genetic information (messenger RNA), but Flynn’s work has show that it has other functions critical to basic processes in the cell.
As we’ve been hearing on the program, biology has largely been a science of inventory. Throughout today’s conversation, Flynn argues that molecular organization itself may be a fundamental biological variable. Not simply whether a molecule exists, but where it exists, what it is adjacent to. Using technologies such as Pixelgen’s Proximity Network Assay, his lab is beginning to map the “cell surface architecture,” or the arrangement of proteins, glycans, and nucleic acids that together govern signaling and cellular behavior.
The implications stretch across biology. Flynn describes early evidence that extracellular RNA can tune classical signaling pathways such as VEGF-mediated angiogenesis by physically modulating how growth factors engage receptors on endothelial cells. Remove the RNA, and growth factor binding changes dramatically. Rather than acting as a simple on/off switch, the RNA appears to function as a finely tuned regulatory layer controlling signaling strength.
In cancer, where cell-surface signaling drives growth, invasion, and immune escape, looking at the organization of the cell surface may determine whether therapies can physically access their targets. Flynn points to bispecific antibodies and T-cell engagers as examples of drugs whose function already depends on proximity and molecular arrangement, even if work in biology has not fully measured those variables before.


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For decades, biology has been driven by the powerful notion that if we could sequence enough genomes, transcriptomes, epigenomes, then we could finally explain the cell. On today’s show, Gary Schroth, the Chief Scientific Officer at Cellanome, argues that something essential was still missing.
Schroth spent nearly two decades at Illumina helping build the sequencing revolution. He has now joined Cellanome to pursue an expanded vision of biology that connects transcriptomics with live-cell imaging. Our conversation centers around two newly released preprints describing the company’s platform and its application to CRISPR screening, where imaging and transcriptomic data are explicitly linked in the very same cells.
“What we show in a few examples in both papers,” Schroth explains, “is that it’s the combination of transcriptome information and imaging information that really gives us the complete story of what that cell is doing.”
That idea—linking what researchers literally see under the microscope with the molecular state of the exact same cell—emerges as the core concept of the interview. Rather than treating imaging and transcriptomics as separate measurements, Cellanome brings them together in a longitudinal workflow where cells can be observed alive over time and then profiled at the transcriptomic level.
“Sequencing has certainly taught us a lot about cells and sort of the parts list inside cells,” he says. “But it doesn’t really explain biology.”
Will this be the next phase of post-genomic biology where the field moves beyond static snapshots toward directly observing cellular function as it unfolds?


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