Groundbreaking Living Brain Project challenges decades of assumptions in neuroscience

In a revealing Genomic Press Interview published today in Genomic Psychiatry, Dr. Alexander W. Charney describes how treating patients with schizophrenia transformed his scientific pursuits from abstract questions to an urgent mission, ultimately leading to discoveries that challenge fundamental assumptions in neuroscience research.

The interview explores Dr. Charney's creation of the groundbreaking Living Brain Project at Mount Sinai, which has collected over 300 brain tissue samples from living patients undergoing neurosurgery. His team's findings reveal a startling reality: 80% of genes exhibit different expression levels in living versus postmortem brain tissue, calling into question decades of neuroscience research based primarily on postmortem samples.

From big questions to bold solutions

"I am drawn to big questions - how things work, how people work," Dr. Charney explains in the interview. However, it was his direct experience treating patients with schizophrenia that transformed intellectual curiosity into moral imperative. "I was struck by how little we truly understand the brain at a molecular level, particularly when compared to other organs. That gap felt like both a scientific challenge and a moral imperative."

This realization propelled Dr. Charney to build unprecedented research infrastructure. As Director of the Charles Bronfman Institute for Personalized Medicine and Vice Chair of the Windreich Department of AI in Human Health at Mount Sinai, he recognized that achieving his goals required creating entirely new systems. "I moved into leadership as it became clear to me that the systems I needed to accomplish my goals did not exist yet, and no one else was working on building them," he shares.

Pandemic as catalyst

The COVID-19 pandemic emerged as a defining moment in Dr. Charney's career trajectory. Having graduated medical school in 2012 and completed residency in 2018, he represents what he calls "a new generation of leaders in medicine." When the pandemic struck New York City in March 2020, he made the bold decision to redeploy his entire laboratory to the crisis response effort.

This pivot proved transformative, leading to landmark publications in Nature Medicine, Cell, and Science. As Lead Principal Investigator, he secured $22 million for the NIH RECOVER Initiative to study long COVID, demonstrating how crisis can accelerate both scientific discovery and leadership development.

Building tomorrow's medicine today

Beyond the Living Brain Project, Dr. Charney co-directs the Mount Sinai Million Health Discoveries Program, one of America's largest precision medicine initiatives. In partnership with Regeneron Genetics Center, the program will sequence one million patients over five years, with particular emphasis on advancing health equity for underrepresented populations.

The interview reveals Dr. Charney's multifaceted approach to advancing psychiatric care. As Executive Director of the Blau Adolescent Consultation Center for Resilience and Treatment and Head of the Brain and Data Sciences Lab, he integrates artificial intelligence and machine learning to accelerate therapeutic development. His team's work spans psychiatric genomics, computational psychiatry, and multi-omics analysis.

A lifelong mission

Throughout the interview, Dr. Charney's ultimate goal remains clear: developing cures for severe mental illnesses like schizophrenia. "My lifelong goal is to develop cures for severe mental illnesses like schizophrenia. Everything I do in my career is with an eye towards that goal," he states, referencing his team's recent Nature Genetics publication on the subject.

The interview also captures a lighter moment from a Mount Sinai retreat, where Dr. Charney interviewed Ameca, described as the world's most advanced humanoid robot. This interaction, showcasing the robot's lifelike expressions and conversational abilities, embodied the institution's bold vision for AI's role in healthcare's future.

Values and vision

When discussing the scientific community's challenges, Dr. Charney doesn't mince words about what he sees as a fundamental problem: "We have a crisis of reproducibility driven by researchers prioritizing personal prestige over finding solutions for patients." His commitment to scientific rigor permeates his approach, as he emphasizes the importance of questioning assumptions and ruling out all alternative explanations before accepting findings.

Outside the laboratory, Dr. Charney finds balance through long-distance sea kayaking, describing his love for spending time on rivers, lakes, and oceans. His favorite possession, a Gibson J-200 acoustic guitar named Gertrude, hints at the creative outlets that complement his scientific pursuits.

Dr. Alexander W. Charney's Genomic Press interview is part of a larger series called Innovators & Ideas that highlights the people behind today's most influential scientific breakthroughs. Each interview in the series offers a blend of cutting-edge research and personal reflections, providing readers with a comprehensive view of the scientists shaping the future. By combining a focus on professional achievements with personal insights, this interview style invites a richer narrative that both engages and educates readers. This format provides an ideal starting point for profiles that explore the scientist's impact on the field, while also touching on broader human themes. More information on the research leaders and rising stars featured in our Innovators & Ideas – Genomic Press Interview series can be found in our publications website: https://genomicpress.kglmeridian.com/.