The Living Brain Project: Upending decades of neuroscience

In the world of medical research, few journeys feel as personal and urgent as that of Dr. Alexander W. Charney. His career began with curiosity, but patient care reshaped it into a mission. A recent interview published in Genomic Psychiatry shows how his work has upended decades of neuroscience and is redefining the study of the human brain.

Dr. Charney, who treats patients with schizophrenia, quickly learned that the brain holds more mysteries than most other organs. While the heart, lungs, and kidneys are mapped in detail, the brain remains elusive at the molecular level. "I was struck by how little we truly understand the brain at a molecular level, particularly when compared to other organs," he said. "That gap felt like both a scientific challenge and a moral imperative." His answer to this challenge was the creation of the groundbreaking Living Brain Project at Mount Sinai, which has already changed neuroscience in surprising ways.

The Living Brain Project is the first large-scale effort to study fresh brain tissue collected during neurosurgery. To date, the project has gathered over 300 samples from living patients. The results are striking: 80% of genes show different expression levels in living versus postmortem brain tissue.

This single finding challenges decades of neuroscience research, much of which relied on frozen samples taken after death. If the molecular signals of a living brain are so different, then countless conclusions built on old methods may need rethinking.

By questioning assumptions, Dr. Charney and his team have redefined what reliable brain data looks like. "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 explained. This leadership included not only directing the Charles Bronfman Institute for Personalized Medicine but also serving as Vice Chair of the Windreich Department of AI in Human Health.

The COVID-19 pandemic forced many researchers to rethink their work. For Dr. Charney, it became a turning point. After completing medical school in 2012 and finishing his residency in 2018, he still described himself as part of "a new generation of leaders in medicine."

When New York City faced its first surge in March 2020, he redeployed his entire lab to fight the virus. The pivot was bold but fruitful. His team published key studies in Nature Medicine, Cell, and Science. Soon after, he became Lead Principal Investigator for the NIH RECOVER Initiative, securing $22 million to study long COVID.

This effort revealed how crisis can accelerate discovery. What began as a temporary pivot turned into one of the most significant phases of his career. It also cemented his reputation as a leader who could act quickly when science and public health demanded it.

The Living Brain Project is not Dr. Charney’s only bold initiative. He also co-directs the Mount Sinai Million Health Discoveries Program. This program, created with the Regeneron Genetics Center, plans to sequence one million patients over five years. It focuses on expanding precision medicine while ensuring diverse populations are represented.

Precision medicine aims to tailor treatments to individual genetic profiles rather than offering one-size-fits-all care. By analyzing DNA from such a large group, scientists hope to better understand not just common diseases but also the health challenges faced by underrepresented communities.

At the heart of his work is a mission that has never changed: finding cures for severe mental illness. Schizophrenia, a condition that disrupts thought and emotion, remains central to his research. "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 said.

His team recently published findings that could advance this mission. By applying computational psychiatry, psychiatric genomics, and multi-omics analysis, they aim to bring new treatments into reach. Artificial intelligence also plays a role, helping analyze massive amounts of brain data faster than traditional methods would allow.

Dr. Charney’s leadership is not limited to science. He directs the Blau Adolescent Consultation Center for Resilience and Treatment and heads the Brain and Data Sciences Lab at Mount Sinai. His efforts combine mental health care with data-driven solutions, ensuring the next generation of medicine is both humane and high-tech.

He is also unafraid to call out weaknesses in the scientific community. "We have a crisis of reproducibility driven by researchers prioritizing personal prestige over finding solutions for patients," he said. His commitment is to rigor, questioning assumptions until all alternatives are ruled out.

Science often feels abstract, but Dr. Charney’s story highlights its human side. At a Mount Sinai retreat, he even interviewed Ameca, described as the most advanced humanoid robot in the world. The robot’s lifelike expressions and speech embodied his institution’s vision for AI in medicine.

Outside of work, he seeks balance through long-distance sea kayaking on lakes, rivers, and oceans. His favorite possession, a Gibson J-200 acoustic guitar named Gertrude, reflects his creative side. These moments show how personal passions can fuel resilience in high-pressure careers.

The interview featuring Dr. Charney is part of the "Innovators & Ideas" series, which explores the lives of scientists shaping today’s discoveries. By mixing personal insight with cutting-edge research, the series reminds us that science is built not just on data but also on values, vision, and determination.

In Dr. Charney’s case, the message is clear: transforming brain research requires more than tools. It requires urgency, leadership, and the willingness to build what does not yet exist. The Living Brain Project and his work on precision medicine prove that redefining neuroscience is not just possible—it is already underway.

Note: The article above provided above by The Brighter Side of News.

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