Mendelspod Podcast

Coming from the field of digital pathology, Joachim Schmid has a unique perspective on the evolution of multi-omics.  Schmid was recently appointed as Vice President of Multiomics Data Solutions at Illumina.In this episode, Theral dives into the burgeoning field of multi-omics—integrating data from various omic layers such as genomics, proteomics, and transcriptomics—and the massive data challenges that come with it. Schmid discusses how sequencing costs are plummeting, leading to an explosion in multi-omics applications. Yet, with all the data being generated, biologists often lack the computational background to make sense of it.  Schmid highlights Illumina's acquisition of Partek, a company that has been developing multi-omics data analysis tools for over 30 years, and he emphasizes that empowering researchers with accessible analysis tools is crucial to advancing the field.AI is poised to play a key role in moving multi-omics forward. Schmid discusses both the opportunities and limitations of AI, noting that while AI can streamline data processing, there are still areas for improvement, particularly in developing more intuitive and user-friendly tools for biologists. He shares some exciting applications of multi-omics in personalized medicine and cancer research.

Dr. Mark Lewis is a well known GI oncologist at Intermountain Health in Salt Lake City, Utah. Gifted with a passionate communication style, he has over 93,000 Twitter followers. Next month, he will live-tweet his upcoming colonoscopy.  

In this episode, Dr. Lewis joins Theral in our ongoing series on minimal residual disease (MRD) testing, a revolutionary blood test that is helping detect residual cancer causing a paradigm shift in patient management.

Dr. Lewis belongs to a pioneering group that allows oncologists to specialize in a single cancer type. He says MRD testing has transformed his own practice, describing how this “liquid biopsy” approach, previously common in hematology, is also advancing the detection of solid tumors.

“News flash,” he says in today’s show. “We were trained a certain way.  My training ended 12 years ago, and I had fantastic training.  I did my fellowship at the Mayo Clinic.  But if I practiced now the way I was trained then, my patients would be so underserved, almost to the point of malpractice.”  

Dr. Lewis considers MRD testing a key part of his own standard of care and anticipates its broader adoption among GI oncologists. He also highlights the recent findings from the GALAXY study, which shows improved survival rates for patients utilizing MRD testing, underscoring its potential to reshape GI oncology practices in the near future.

When Bill Clinton announced the sequencing of the human genome in 2000, the New York Times ran the following headline on the front page: "Genetic Code of Human Life is Cracked By Scientists.”We’re still living up to that headline.

Ed Abrahams has led the Personalized Medicine Coalition (PMC) for twenty years. Before his retirement in December, we asked him to join us to reflect on his tenure and take stock of the field. PMC was established as a “catalyst” and organizer to bring the various stakeholders in personalized medicine together and do the human work that science and business were missing.Ed tells Theral that the political problem may be more difficult than the science. Even with the scientific breakthroughs, he says that what Biden called his Cancer Moonshot has proved more difficult than actually going to the moon!Ed traces the field’s roots back to the groundbreaking announcement of the Human Genome Project and reflects on the significant strides in personalized drug development, which now represents over a third of recent drug approvals, as well as breakthroughs and difficulties on the diagnostics side.Current challenges are regulation in the second Trump era and the persistent practice gap, but Ed ends with excitement for what’s next.The Personalized Medicine Coalition hosts its annual conference in Boston this week, Nov 13-14th.  They have just announced their new president to be Amy Nicole Nayar, formerly Vice President for U.S. Patient Advocacy & Government Affairs at Novartis Gene Therapies

In this episode, Theral delves into the groundbreaking role of microRNA as a cancer biomarker with Tim Williams, professor of clinical pathology at the University of Cambridge Veterinary School, and Paola Ulivi, a leading researcher at the Instituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori (IRST) in Italy. MicroRNA, which recently garnered its discoverers a Nobel Prize, has emerged as a powerful tool for detecting and tracking cancer progression.

Williams and Ulivi share their latest research, highlighting how microRNA’s rise in cancer diagnostics parallels the evolution of fragmentomics, which analyzes cell-free and circulating tumor DNA. We explore the key differences between using RNA and DNA in biomarker development, the advancements in tools driving these discoveries, and the timeline for microRNA-based diagnostic tests to reach clinical practice.

“There’s a lot of potential,” says Ulivi, “but the challenge in translating this into clinical practice will be the standardization and normalization of the process."

Join us as we discuss the promise, obstacles, and future of microRNA in transforming how we diagnose and treat cancer.

Jacob Rubens is having quite a career.  Studying at  MIT in the Synthetic Biology Center with Professor Tim Lu, he invented gene circuits that allow engineered cells to do novel analog, digital, and hybrid computations, enabling the emerging field of “intelligent” cell therapies. In 2017, he was honored in Forbes 30 under 30 and, in 2021, in Business Insider’s list of 12 young serial entrepreneurs building the next generation of biotech. He has co-founded Kaleidoscope Biosciences, Sana Biotechnology, and the focus of today’s interview, Quotient Therapeutics.To understand what Quotient is up to, we must go back to basic biology and remember what are somatic genomics.  Germline mutations are changes to your DNA inherited from the egg and sperm cells during conception. Somatic mutations are changes to your DNA that happen after conception to cells other than the egg and sperm. These somatic mutations can lead to genetic conditions that affect your health. In truth, our bodies contain not one but trillions of divergent genomes, the sum of which we can call our “somatic genome.” Quotient Therapeutic studies this library of variant genomes that contains vastly more genetic information than we ever thought possible. In today’s show, Rubens says that the rise of somatic genomics offers a revolution in biology and that his company has a step up on those now getting excited about the field, including $100 million being invested by the NIH in this area of genomics.”This is some of the coolest science I have seen in my career,” says Rubens.   "The somatic genome is a revolutionary alternative view of what is going on in every cell.  All 30 trillion cells in our bodies have a distinct sequence of DNA. Two cells sitting next to each other may differ by thousands of base pairs.”Rubens says this new biology will lead to many new targets for drug discovery as well as biomarkers for diagnostics. How far has the company developed their platform—where are they at today?  Which disease areas are they pursuing for new drugs? Is the company itself pursuing drug development?  Join us as we explore somatic genomics in our series, “The New Biology.”

Human genomics is complex. With new, scalable tools, we are unraveling that complexity. For example, we don’t just each have one genome; we have trillions, as each cell has a unique genome. Analyzing biology at the single-cell level continues to be one of the major frontiers in research.

To learn how Single Cell Discoveries (SCD), a contract research organization in Utrecht, the Netherlands, has scaled and innovated in this field, Theral sits down with Mauro Muraro, cofounder and CEO of SCD. Muraro discusses the company's origins as a small university lab and its rapid growth due to increasing demand for single-cell and multiomic applications in biotech and pharma.

The conversation delves into the transformative potential of single-cell technologies, addressing key topics like identifying rare cell types, single-cell atlases, and the challenges of handling the enormous data generated from these analyses. Muraro explains how Single Cell Discoveries is advancing the field with cutting-edge techniques, such as spatial transcriptomics and high-throughput sequencing, to push the boundaries of biological research and drug discovery.

Why does a single cell require such a large sequencing capacity? What are the challenges in finding new higher-quality targets for pharma?  And how does SCD aim to push the boundaries of current single-cell technologies?

One of the ways SCD helps pharmaceutical companies is by stratifying tissue by cell type to better find targets that will work. Muraro tells of a client working on neurodegenerative diseases who says, "It’s like doing a clinical trial in a dish."

Vik Bajaj is bullish on genomics in the age of artificial intelligence. A pioneering figure in biotech—co-founder of Verily and Grail—Bajaj now leads Xaira Therapeutics, where he's exploring how AI can revolutionize drug development. In today’s episode, he joins Theral to break down how the intersection of AI and genomics is unlocking new possibilities in drug development, with the potential to accelerate every stage of drug discovery.

Bajaj explains that at Xaira, machine learning and advanced modeling enable drug development to happen almost entirely in silico. By simulating biological systems and predicting drug interactions, AI could dramatically cut the time and cost of traditional methods.

However, there are still hurdles, especially the need for more robust genomic datasets to better understand causality. Bajaj discusses how Xaira Therapeutics is addressing this gap, driven by an ambitious vision to harness AI for breakthroughs that could reshape the field.

What are the most exciting applications of AI in biotech today? And what does Bajaj see as the biggest challenges ahead? We even ask for his thoughts on unified information theory—a concept that could integrate biology, AI, and computational science for a more comprehensive approach to human health.

Join us as we take a broad look into what’s happening now in AI-driven biotech with one of the field’s leading innovators.

Singular Genomics launched its fast and flexible mid-throughput sequencing platform, the G4, in the heady days of the pandemic when we saw a renaissance in new technologies and companies.

At AGBT earlier this year, the company unveiled its latest offering in development, the G4X Spatial Sequencer, an upgrade to the G4 that unlocks the system to perform high-throughput in situ multiomics.  The platform will be capable of simultaneous direct RNA sequencing, targeted transcriptomics, proteomics, and fluorescent H&E from FFPE tissues at subcellular resolution. The G4X positions Singular to be the only company worldwide to offer capabilities for tissue-based in situ spatial multiomics and NGS on the same instrument.Singular's CEO, Drew Spaventa, joins us to discuss the G4X platform and the latest evolution in spatial biology.Drew says the field of spatial biology is a billion-dollar market, is growing rapidly, and the platform hits a sweet spot for throughput to bring down running costs. "The biggest issue people have right now in spatial is throughput cost per sample,” says Drew.  “It’s prohibitively expensive.”What early applications does the company see in their early service work?  When will the instrument be available?  And how does Drew see research evolving in the next couple years?

Ellen Matloff is back on the show today to discuss the changing landscape of genetic testing and counseling in 2024. She is the founder and CEO of MyGeneCounsil and a strong advocate for the critical role of genetic counselors in healthcare. She also writes a regular column for Forbes magazine.In 2024, we’ve seen a dramatic transformation of the genetic testing landscape, with big labs buying the small ones. Ellen says this is “forcing genetic testing to go mainstream.”Surely that’s a good thing. Ellen parses through the good, the bad, and the ugly of the recent changes in the field. We mostly focus on the role of the genetic counselor, for which Ellen has some ideas.

Ellen will be discussing this further with a panel at the upcoming Precision Oncology and Diagnostics 2024 in Chicago.

Depending on your age, DNA sequencing is experiencing a second or third renaissance. New sequencing tools continue to make genomics one of the fastest-growing industries of all time. All this scaling can create a bottleneck in sample prep. Volta Labs, a company founded out of the MIT Media Lab by Udayan Umapathi, has just commercialized a new instrument for sample prep called Callisto. The instrument manipulates samples with electric, magnetic, and acoustic fields.   

Udayan joins us today to describe the new instrument and comment on how sample prep is evolving today. Most importantly, the company wants to develop new apps with customized settings based on the customer's particular application, such as isolating really long, high-molecular-weight DNA for long-read sequencing. 

“The vision is to have a vast set of apps, similar to an iPhone.  We will continue to provide more and more apps that cater to various customers,” says Udayan in today’s show.

What are the apps Udayan sees in the next few years?  And what is the ultimate sample prep in today’s world of sequencing?