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The Fitzgerald Laboratory research centers on cardiovascular disease, cholesterol metabolism and innate immunity. This effort is anchored by investigation of the efflux transporter ABCA1, which exports cholesterol and phospholipid from cells in the first step of HDL biogenesis. HDL is a lipoprotein whose blood level is inversely correlated with cardiovascular disease. Tangier patients with ABCA1 mutations develop premature vascular disease, peripheral neuropathies and lack circulating HDL. ABCA1 poly-morphisms are also of diagnostic interest, since they exert a strong influence on HDL levels in the general population.
Additionally, we investigate how HIV infection and antiretroviral treatment can alter HDL function and cardiovascular disease risk. Here the Fitzgerald Laboratory has developed methods to profile HDL from HIV positive individuals using mass spectrometry methods to quantitate protein and lipid content in this athero-protective lipoprotein. Additional work has analyzed how the HIV Nef protein reprograms macrophage lipid metabolism to maximize virion envelope production. Importantly, we have found that activation of the LXR nuclear hormone receptor strongly inhibits viremia in a humanized mouse model of HIV disease.
Finally, we are analyzing the mechanisms by which formation of cholesterol crystals in the artery wall can incite inflammatory processes through molecular pathways that involve a cellular multi-protein complex termed the “inflammasome”. This collaborative work with the laboratory of Eicke Latz has suggested cyclodextrin, a carrier molecule for hydrophobic drugs, has potential to be repurposed as an anti-atherosclerotic therapy that, in part, reprograms macrophage LXR transcriptional networks.
Michael L. Fitzgerald, PhDMichael Fitzgerald, PhD is an Assistant Professor of Medicine at Harvard Medical School and a faculty member in the Lipid Metabolism Unit of the Department of Medicine at Massachusetts General Hospital.
Min Hi Park, PhDResearch Fellow
Victoria Hawxhurst, BSResearch Technician
Zahedi Mujawar, PhDTraining Period: 2007-2016American Heart Association Research Fellow
Norimasa Tamehiro, PhDTraining Period: 2006-2016Uehara Research Fellow
Debbie Zhuang, BSTraining Period: 2006-2008 Current Position: Analyst, ClearView Healthcare Partners
Cari Brown, MDTraining Period: 2005-2007 Current Position: Obstetrics & Gynecology, Mount Auburn Hospital
Suiping Zhou, PhDTraining Period: 2005-2007Current Position: Senior Research Investigator, Institute for Environmental Medicine, University of Pennsylvania
R01HL112661-01Contact PI: Fitzgerald ML; mPI: Latz, E9/1/12 - 6/30/17NIH/NHLBI
This basic and translational grant explores the relationship between HIV infection, anti-retroviral therapy, and the ability of HDL to prevent vessel wall cholesterol crystal inflammation.
R01 HL101274-01A1Co-PI: Fitzgerald ML; Contact PI: Bukrinsky, M7/1/10-12/31/16NIH/NHLBI
This grant explores the role that HIV infection and antiretroviral drug therapy play in causing dyslipidemia and increased risk of cardiovascular disease in HIV positive individual. The role of the Fitzgerald lab is to develop a HDL proteomic and lipid profiling procedure to monitor changes in HDL composition during the acute infection period and subsequent drug treatment phase.
Michael L. Fitzgerald, PhDLipid Metabolism UnitCenter for Computational and Integrative BiologyMassachusetts General Hospital/Harvard Medical SchoolSimches Research Building185 Cambridge Street, Room 7214Boston MA 02114-2790
Office Phone: 617-726-1465Lab Phone: 617-724-0439
Email Dr. Fitzgerald
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