Assistant Professor @CDN
Department of Psychiatry
Department of Genetics and Genomic Sciences
Icahn School of Medicine at Mount Sinai
Computational Neuroepigenomics Group @ Center for Disease Neurogenomics (CDN)
I’m interested in how genetic risk for psychiatric and neurodegenerative disease is encoded in the human genome and how this risk manifests as specific molecular programs in the brain. Rather than thinking about disease in terms of individual genes, my work asks how groups of regulatory programs emerge in particular cell types and how these programs change across the human lifespan.
What especially motivates my work is the question of timing. Many psychiatric disorders, including schizophrenia, are highly heritable, yet clinical symptoms such as psychosis typically do not appear until adolescence or early adulthood, when the brain is still maturing. This raises a fundamental question: if genetic risk is present from birth, what drives the delayed onset of disease? Which cell types become vulnerable, and which molecular mechanisms shift during development to unmask this risk?
I pursue similar questions in neurodegenerative disease, where genetic and regulatory vulnerabilities may remain latent for decades before becoming biologically consequential with aging. By studying cell-type–specific regulatory architecture across development, adulthood, and aging, my goal is to understand which parts of the genome become vulnerable over time and how these changes contribute to disease onset and progression.
My research is centered on understanding how genetic variation shapes brain function across the human lifespan, and how this variation gives rise to vulnerability in psychiatric and neurodegenerative diseases. I take a mechanistic, genome-wide view of disease risk, focusing on how molecular programs emerge in specific brain cell types during development, mature through adulthood, and become destabilized with aging.
This is a highly data-driven research effort, grounded in the integration of large-scale human postmortem brain datasets from multiple brain regions. As new data are produced, we systematically examine regulatory and epigenomic programs across diverse cell types to identify those that are selectively vulnerable in psychiatric and neurodegenerative disease. A complementary goal of this work is to connect shared and region-specific molecular programs across distinct brain regions, providing an integrated, systems-level view of disease biology.This work is led by Hui Yang, Lyra Sheu, Swadha Singh and Chinwe Nwaneshiudu from our team.
In parallel, our team study the regulatory architecture of the healthy human genome across development, adulthood, and aging. By mapping chromatin accessibility and gene regulation in specific brain cell types, this project seeks to define how molecular programs normally emerge, stabilize, and decline over time. This provides a critical reference for distinguishing disease-related changes from normal developmental and aging processes.This work is led by Hui Yang from our team.
Tandem repeats (TRs)—short DNA motifs repeated consecutively—are highly polymorphic elements that comprise approximately 6% of the human genome, far exceeding the ~2% devoted to protein-coding sequences. Variation in TR length is known to influence gene expression, RNA splicing, and chromatin structure, positioning these elements as powerful regulators of genome function.Despite their abundance and functional impact, tandem repeats and other repetitive elements have been largely overlooked in large-scale genetic studies, which have focused predominantly on single-nucleotide polymorphisms. As a result, the contribution of these highly mutable genomic elements to psychiatric and neurodegenerative disease risk—and to missing heritability more broadly—remains poorly understood. This work, led by Christian Dillard as part of our team, aims to address this gap by integrating repeat variation with cell-type–specific regulatory and epigenomic maps of the human brain.
30+ publications | View all on PubMed
Nature Neuroscience (2025) 28:2451–2460
Population-scale chromatin accessibility profiling (N = 1,393) of neurons and non-neurons from human neocortex reveals that schizophrenia-associated regulatory programs are strongly linked to early fetal brain development and enriched for genetic risk loci.
Nature Neuroscience (2022) 25:474–483
Integrated histone modification landscapes from 739 adult prefrontal cortex samples to map coordinated regulatory domains, revealing disease-associated restructuring of 3D genome organization enriched for schizophrenia heritability.
Nature Neuroscience (2018) 21:1126–1136
Generated cell-type–specific histone modification maps from human frontal cortex, directly linking schizophrenia genetic risk to neuronal epigenomic signatures.
Biological Psychiatry (2022) 92:443–449
Review synthesizing emerging evidence linking epigenomic regulation, chromatin structure, and schizophrenia risk.
medRxiv (2025)
Single-cell transcriptomic profiling of 1.3 million cells across the human lifespan, revealing continuous developmental and aging trajectories across neuronal and glial populations.
Nature Neuroscience (2022) 25:1366–1378
Integrated chromatin accessibility and 3D genome architecture to identify regulatory reorganization in Alzheimer's disease cortex.
University of Illinois Urbana-Champaign
Urbana-Champaign, Illinois, USA
Technical University of Munich
Munich, Germany
Punjab Engineering College
India