In this episode of Let’sTalk About That, Anirvan Ghosh speaks with Jason Coloma, CEO of Maze Therapeutics, about what it really takes to build a biotech company at the intersection of human genetics, precision medicine, and long-term value creation.

Jason brings a rare end-to-end perspective—spanning big pharma, venture creation, and public company leadership. The conversation traces how Maze was conceived at Third Rock Ventures around a simple but powerful idea: move beyond statistical genetic associations and use human genetics to deeply understand disease biology, identify protective variants, and design medicines that mimic nature’s own experiments.

Using kidney disease as a central case study, Jason explains how Maze translates genetic risk and protective variants into concrete drug targets—and why this approach may finally unlock progress in complex, common diseases that have resisted traditional drug discovery. The discussion also explores the realities of company building: choosing focus over breadth, making hard portfolio decisions in capital-constrained markets, partnering and spinning out programs, and navigating board and investor dynamics.

Jason reflects candidly on leadership under uncertainty, the challenges of going public in a volatile biotech market, and why clarity of vision matters more than consensus in leading a new company.

In this episode of Let’s Talk About That, Anirvan Ghosh speaks with Monica Coenraads, a transformative leader in the raredisease community whose work has reshaped the field of Rett syndrome, a severe neurodevelopmental disorder.

Monica’s journey began as a parent, after her daughter Chelsea was diagnosed with Rett syndrome at a time when little was known about the disease and the causative gene, MECP2,had not yet been identified. Faced with limited answers and no treatments, Monica set out to understand the science—and soon recognized the need for a new, research-driven model.

She went on to found the Rett Syndrome Research Trust (RSRT),raising more than $125 million to accelerate rigorous, collaborative science. A pivotal moment came in 2007, when research funded by RSRT demonstrated that restoring MECP2 in animal models could reverse Rett symptoms—even later in life—fundamentally changing how the disease was understood.

In this conversation, Monica describes how RSRT built globalresearch consortia, catalyzed gene therapy programs now in the clinic, and is advancing next-generation approaches to cure Rett Syndrome.

It is a powerful story about resilience, scientific focus, and how determined leadership can turn a devastating diagnosis into a credible path toward cures.

In this episode of Let’s Talk About That, Anirvan Ghosh is joined by Gilmore O’Neill, President and CEO of Editas Medicine, for an in-depth conversation at the frontier of genetic medicine, neuroscience, and biotech leadership.

Gilmore traces his journey from clinical neurology at Mass General to a career in biopharma driven by frustration with the lack of effective treatments for devastating neurological diseases. He reflects on formative years at Biogen, where first-principles thinking—deep attention to human biology, PK/PD, and disease pathology—helped enable breakthroughs such as Spinraza for spinal muscular atrophy and transformative therapies in multiple sclerosis.

The discussion then turns to the rise of genetic medicines, from antisense oligonucleotides to gene therapy and, ultimately, gene editing. Gilmore offers a clear, accessible explanation of how CRISPR-based in vivo gene editing differs from traditional gene delivery—and why Editas is focused on single-dose, durable therapies that can be delivered with minimal healthcare infrastructure.

A major focus is Editas’s lead program targeting LDL cholesterol, where in vivo gene editing has shown unprecedented reductions in LDL levels in preclinical models. Gilmore outlines the scientific rationale, the public health implications of treating common diseases with genetic medicines, and what it will take to translate this technology safely into humans.

A thoughtful conversation on innovation, rigor, and reimagining medicine beyond chronic treatment.

In this episode of Let’s Talk About That, Anirvan Ghosh speaks with Andreas Wallnoefer, whose career spans the full arc of drug development—from early clinical research to senior R&D leadership at Roche, and later to venture investing and biotech board roles.

Andreas reflects on more than 25 years in big pharma, where he helped shape early translational medicine and confronted one of the field’s enduring challenges: why clinical success rates remain low despite enormous advances in science, biomarkers, and technology. He shares lessons from pioneering early human pharmacology, the importance of truly understanding mechanism of action, and why many drugs fail when commercial priorities override biology.

The conversation then turns to Andreas’s transition from Roche to venture capital and company building, including insights from launching and scaling early-stage biotechs. Using the EyeBio story as a case study, he explains why small, focused teams with strong leadership, disciplined decision-making, and aligned investors can often move faster—and succeed more often—than large organizations.

Looking ahead, Andreas discusses the types of companies and technologies that excite him today, from gene therapy and neurology to immunology and ophthalmology. Throughout the discussion, a clear theme emerges: breakthrough medicines require not just great science, but courage, persistence, and leaders willing to challenge conventional wisdom.

Host Anirvan Ghosh reflects on Season 1 of 'Let's Talk About That', highlighting themes around leadership, science and society, and our shared experiences as a nation of immigrants

Dr. Carla Shatz is one of the most influential neuroscientists of our time, whose work has fundamentally shaped our understanding of brain development and plasticity. She is the Sapp Family Provostial Professor of Biology and Neurobiology at Stanford University, a member of the National Academy of Sciences, and recipient of the Kavli Prize in Neuroscience.

In this episode, Carla sits down with Anirvan (who worked with her as a graduate student) to talk about her scientific journey, the work from her lab that revealed how early patterns of neural activity sculpt brain circuits during critical periods of development, and the surprising discovery that the developing brain uses spontaneous waves of activity—even before birth—to refine its wiring.

She also discusses how that investigation revealed an unexpected connection between the immune and nervous systems, and how an immune protein, PirB, plays a role in sculpting developing neural circuits. Remarkably, PirB can bind to beta-amyloid in an adult brain, suggesting an unexpected link with Alzheimer's disease and potential therapeutic strategies.

Scott Illingworth is a director, educator, and creative force who bridges theatre and social engagement. Much of his work focuses on new and adapted works that bring urgent human stories to the stage.

In this conversation, Scott sits down with Anirvan to discuss his work in capturing immigrant stories through the Verbatim Salon, a monthly event in New York City where actors perform real stories from people navigating the U.S. immigration system. He shares insights into the collaborative process of theater-making, the importance of storytelling in understanding the immigrant experience, and the emotional depth of the narratives presented.

The stories we hear of immigrants speaking of their experiences - an muslim woman who escaped conflict in Afghanistan, a central American man who came over as a young child, and a Ukrainian woman who came to the U.S. after the Russian invasion, highlight the complexities of identity and belonging, emphasizing the need for empathy and understanding in addressing immigration issues in America.

In this episode, Dr. Arshad Khanani sits down with Anirvan Ghosh to talk about vision loss and what we can do to slow or alter the course of disease.

Dr. Khanani, is one of the world’s leading innovators in retinal disease research and treatment. He is Managing Partner and Director of Clinical Research at Sierra Eye Associates, as well as a Clinical Professor at the University of Nevada, Reno School of Medicine. He has served as principal investigator in over 150 clinical trials and has pioneered first-in-human surgical procedures for sustained drug delivery and gene therapy.
In this wide-ranging conversation Dr. Khanani discusses eye diseases that lead to progressive vision loss, the importance of early detection in diseases that affect the retina such as age-related macular degeneration (AMD), diabetic eye disease, and Geographic Atrophy, and treatment options that can alter disease trajectory. He also discusses recent advances in the field, such as gene therapy, that could fundamentally change the way retinal diseases are treated in the future.

Liz Terrazas is teacher who has recently become engaged in issues of community safety, immigrant rights, and grassroots activism. She grew up in a Mexican-American family in Colorado—her father is from Chihuahua, Mexico, and her mother from Durango, Colorado. After earning her BA in Criminology and Criminal Justice with a minor in Anthropology from Northern Arizona University in 2015, Liz returned to work as a teacher in the Four Corners region of Colorado and New Mexico.

In recent months the Immigration and Customs Enforcement, or ICE—an agency responsible for enforcing immigration laws, conducting deportations, and investigating cross-border crimes, has been particularly active. In response to questions around immigration enforcement, Liz started a grassroots effort to educate community members about their rights, legal protections, and available resources. In this podcast Liz talks to Anirvan about growing up in a Mexican-American community, how immigration enforcement is shaping life in small-town America, and the ways communities are organizing to stay informed and safe.

Dr. Elora López-Nandam is a young evolutionary biologist and a Forbes 30 under 30 honoree, whose work spans the ecology, evolution, and conservation of marine ecosystems. Her work has ranged from studying the sustainability of sea cucumber fisheries in Fiji, to the mysteries of coral bleaching in American Samoa, and how we can restore coral populations. Now, at the California Academy of Sciences, she combines cutting-edge genomics with hands-on aquarium husbandry to guide how we can better steward and reintroduce vulnerable marine life.

In this conversation with Anirvan Ghosh, she talks about the biology and diversity of corals, their role in sustaining marine ecosystems, and how they are being decimated by rising ocean temperatures. She also discusses the fascinating and groundbreaking work she and her colleagues are doing to grow coral in labs and reintroducing them into the oceans to restore coral populations