Overview
My lab uses mouse genetic modeling and molecular and cellular techniques to study basic biochemical pathways of relevance to aging biology.
I. Aging is often accompanied by increases in inflammation. A major interest of the lab is how perturbations in the regulation of autophagy and mitochondrial dynamics in cells are linked to inflammation. One project in the lab focuses on a family of interferon-gamma and LPS regulated proteins, the Immunity Related GTPases (IRGs). The lab has shown that mice and cells lacking one of these proteins, Irgm1, have excessive inflammatory responses that are accompanied by decreases in autophagy and mitophagy, and altered cellular metabolism. IRG genes in human (IRGM) have been linked to several inflammatory diseases including Crohn’s disease and sepsis. Current work in the lab focuses on their role in those diseases using bacterial and relevant mouse models.
II. Altered expression of the cytokine Transforming Growth Factor beta (TGF-b) has been linked with a number of aging processes, including stem cell and neural function. TGF-b is consequently a therapeutic target for a number of age-related diseases. The lab is studying a novel regulator of TGF-b expression called P311, which drives TGF-b translation. Mice have been created that lack P311 and are being used to address the role of P311 in a number of physiological processes.
Current Appointments & Affiliations
Recent Publications
Type I interferon signaling and peroxisomal dysfunction contribute to enhanced inflammatory cytokine production in IRGM1-deficient macrophages.
Journal Article J Biol Chem · November 2024 The human IRGM gene has been linked to inflammatory diseases including sepsis and Crohn's disease. Decreased expression of human IRGM, or the mouse orthologues Irgm1 and Irgm2, leads to increased production of a number of inflammatory chemokines and cytoki ... Full text Link to item CiteIrgm proteins attenuate inflammatory disease in mouse models of genital Chlamydia infection.
Journal Article mBio · April 10, 2024 UNLABELLED: Chlamydiae are obligate intracellular bacterial pathogens that may cause genital pathology via induction of destructive host immune responses. Human-adapted Chlamydia trachomatis causes inflammatory disease in human hosts but is easily cleared ... Full text Link to item CitePosttraumatic stress disorder, trauma, and accelerated biological aging among post-9/11 veterans.
Journal Article Transl Psychiatry · January 6, 2024 People who experience trauma and develop posttraumatic stress disorder (PTSD) are at increased risk for poor health. One mechanism that could explain this risk is accelerated biological aging, which is associated with the accumulation of chronic diseases, ... Full text Open Access Link to item CiteRecent Grants
Duke/UNC ADAR Program
Inst. Training Prgm or CMEMentor · Awarded by National Institutes of Health · 2024 - 2029IRGM proteins as regulators of inflammation
ResearchPrincipal Investigator · Awarded by National Institute of Allergy and Infectious Diseases · 2020 - 2026Role of IRGM proteins in immunity to enteric bacteria
ResearchPrincipal Investigator · Awarded by National Institutes of Health · 2019 - 2025View All Grants