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Matthew Girgenti, PhD

Assistant Professor of Psychiatry
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Assistant Professor of Psychiatry

Biography

Dr. Matt Girgenti is an Assistant Professor of Psychiatry at Yale School of Medicine. He is a neuroscientist and molecular biologist and a member of the Division of Molecular Psychiatry and the Wu Tsai Institute at Yale. He is also a VA-NCPTSD Research Scientist at the West Haven VA Medical Center. He received his doctoral degree at the University of Connecticut in molecular neuroscience. He completed his postdoctoral fellowship in Molecular Psychiatry at Yale followed by a VA Career Development fellowship in postmortem brain genomics. His early research focused on the epigenetic basis of schizophrenia using neural stem cells to demonstrate a role for the SCZ-risk gene ZNF804a as a gene transcription regulator. During his postdoc, his research focused on the cell-type-specific effects of rapid antidepressants, including ketamine and scopolamine using pharmacogenomic approaches. During his VA Career Development fellowship he worked on human postmortem studies focused on the functional genomics of neuropsychiatric disorders, specifically PTSD and major depression. He published the first genome-wide transcriptomic study of the human PTSD brain (Girgenti MJ, et al. 2021). His research now focuses on genomic studies of the postmortem human brain, combining molecular biology and bioinformatics to understand the neurobiology of major brain and behavioral disorders, including depression, PTSD, and alcohol use disorder.

Appointments

Education & Training

PhD
University of Connecticut (2015)
BS
Fairfield University, Molecular Biology (2002)

Research

Overview

While recent large-scale genetic association studies have identified numerous risk loci for PTSD and MDD, the mechanisms through which they contribute to disease remain largely unknown. By applying single cell molecular approaches to the affected tissue (in this case, the human brain), we can uncover novel cellular subpopulations that are associated with these disorders. In parallel, cell type-specific molecular studies allow us to characterize the effect of genetic variation on the complex mechanisms that regulate gene expression in those cells relevant to disease. The goal of our research is to identify causal genes and therapeutic targets relevant to stress-related disorders utilizing human brain derived datasets from frozen postmortem tissue across multiple brain regions and diagnostic groups and couple those with hIPSCs and animal models to understand the neurobiological mechanisms involved.

Current projects include:

  • Cell type-specific genomic atlas of stress disorders- we are currently profiling 2 molecular modalities (transcriptome and epigenome) in 10 human postmortem brain regions across 3 diagnostic cohorts PTSD, MDD, and normal control donors.
  • Functional characterization of PTSD risk variants- here we are expanding upon the rich transcriptomic data generated from our PTSD and MDD postmortem brain tissue by incorporating genome-scale DNA methylation (DNAm) data, alternative splicing, and non-coding RNAs with genetic data to better determine how genetic risk for PTSD and MDD manifests in the human brain.
  • iPSC Functional Validation of PTSD causal genes- we are applying hiPSC-based approaches to manipulate the genotype and/or expression levels of a putative causal risk genes identified in large GWAS and postmortem datasets.
  • Animal models of traumatic and chronic stress- we are validating our molecular findings using a broad array of mouse models and techniques (viral vectors and genetic mutants) in females and males to characterize the behavioral and molecular mechanisms of stress-related disorders.
  • Molecular pathology of suicide- We are identifying cell types, networks, and genes with causal roles in suicide by comparing transcriptomic signatures of PTSD and MDD subjects with or without death by suicide.

Medical Subject Headings (MeSH)

Anxiety Disorders; Behavior and Behavior Mechanisms; Genetics; Genomics; Neurobiology; Neurosciences; Proteomics; Stress Disorders, Post-Traumatic; Stress, Psychological; Suicide; Transcriptome

Research at a Glance

Yale Co-Authors

Frequent collaborators of Matthew Girgenti's published research.

Publications

2024

2023

2022

Academic Achievements & Community Involvement

  • activity

    National PTSD Brain Bank

  • activity

    Faculty Advisory Council

  • activity

    VA National PTSD Brain Bank

  • honor

    Rafaelsen Young Investigators Award

  • honor

    Lawrence Young Investigator Fellow

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