Mount Sinai researcher uncovers how the brain and body interact in aging and depression

In a comprehensive Genomic Press interview published in Brain Medicine today, Dr. Hamilton Se-Hwee Oh reveals groundbreaking insights into the complex dialogue between our brains and bodies that fundamentally shapes aging, depression, and neurodegenerative disease. Working at Mount Sinai's prestigious Brain-Body Institute and Ronald M. Loeb Center for Alzheimer's Disease in New York City, Dr. Oh bridges multiple scientific disciplines to decode mechanisms that could transform treatment approaches for millions suffering from neuropsychiatric disorders.

Personal journey shapes scientific vision

The concept of "sonder" first sparked Dr. Oh's fascination with biology during high school. This profound realization that every person experiences life as vividly and complexly as our own led him to marvel at how trillions of cells coordinate to create rich emotional and subjective experiences. His scientific path gained urgency through personal experience when diagnosed with a rare chronic kidney disease and witnessing his best friend develop persistent, unexplained abdominal pain.

"I hoped that by studying the intricate inner workings of life, I might one day contribute to curing the kinds of conditions that cause such deep and often invisible suffering," Dr. Oh explains in the interview. This personal motivation drives his current research examining how immune cells and metabolic organs amplify or dampen mood symptoms.

Revolutionary discoveries transform understanding of aging

During his Stanford PhD under Dr. Tony Wyss-Coray, Dr. Oh achieved remarkable breakthroughs that reshaped scientific understanding of human aging. His research demonstrated that human organs age at dramatically different rates, with profound implications for disease susceptibility. These findings, published in three first-authored papers in Nature and Nature Medicine, reveal why some individuals develop heart disease while others face neurodegeneration despite similar chronological ages.

Perhaps most significantly, Dr. Oh identified cerebrospinal fluid synaptic biomarkers capable of predicting Alzheimer's dementia onset years before clinical symptoms manifest. This discovery opens possibilities for early intervention strategies that could alter disease trajectories. How might healthcare systems adapt if we could identify Alzheimer's risk decades before symptoms appear?

Bridging brain and body systems

Dr. Oh's current research at Mount Sinai investigates bidirectional communication between the brain and peripheral organs under the mentorship of Drs. Scott Russo and Alison Goate. His work reveals that depression involves far more than brain chemistry alone. By integrating large-scale human proteomics, single-cell transcriptomics, and mechanistic animal models, he demonstrates how psychological stress accelerates organ aging while peripheral molecular signals rewire neural circuits affecting mood and cognition.

This multidisciplinary approach positions Dr. Oh at the forefront of precision medicine development. His research examines molecular fingerprints of interventions including exercise and ketamine therapy, seeking to understand why certain treatments work for specific individuals while failing for others. Could peripheral blood markers eventually guide personalized depression treatment selection?

From stem cells to systems biology

Dr. Oh's scientific evolution reflects broader shifts in biomedical research. Initially drawn to stem cell research at UCLA for its regenerative potential, he noticed inflammation appearing across diverse diseases from cancer to heart disease. This observation led him to study hematopoietic stem cells in Dr. Hanna Mikkola's laboratory, investigating how transcription factors regulate immune system development.

His transition to studying brain-immune interactions emerged from recognizing that external environmental cues profoundly influence cellular identity and function. This systems-level perspective now guides his investigation of how metabolic organs and immune cells shape emotional states and cognitive function. What other unexpected organ systems might influence brain health in ways science has yet to discover?

Implications for future therapeutics

The implications of Dr. Oh's research extend beyond academic discovery. By revealing how specific proteins and metabolites track with depressive behavior, his work identifies novel therapeutic targets. Understanding differential organ aging patterns could enable interventions targeting root causes rather than symptoms alone. His research on exercise and ketamine's molecular mechanisms provides frameworks for developing next-generation treatments.

Major depressive disorder affects multiple body systems, yet current treatments primarily target brain neurotransmitters. Dr. Oh's findings suggest that effective therapies might need to address peripheral inflammation, metabolic dysfunction, and organ-specific aging processes. How might psychiatric care transform if clinicians routinely assessed organ aging profiles alongside traditional mental health evaluations?

Advancing scientific culture

Beyond his research contributions, Dr. Oh advocates for transforming scientific funding priorities. He notes that while scientists celebrate unconventional thinking and groundbreaking discoveries, funding agencies often favor incremental research with substantial preliminary data. This disconnect may limit transformative discoveries that require high-risk exploration.

Dr. Oh particularly values academic freedom to pursue unexpected leads and develop new skills, even when this temporarily reduces productivity. His career trajectory from stem cell biology to computational aging biology exemplifies how interdisciplinary exploration can yield unexpected breakthroughs. What revolutionary discoveries might emerge if funding structures better supported exploratory research?

Dr. Hamilton Se-Hwee Oh'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/.