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Dan LittmanHelen L. and Martin S. Kimmel Professor of Molecular Immunology, Department of Pathology
Professor, Department of Microbiology
Our laboratory investigates 1) the molecular events underlying T-lymphocyte differentiation and activation and 2) how the human immunodeficiency virus (HIV) enters target cells and causes systemic depletion of helper T cells. In both areas, we study the functions of T-cell surface molecules and their interactions with intracellular signal transducing components.
During development, CD4 and CD8 glycoproteins are co-expressed on immature thymocytes (double-positive cells), which are then selected according to their ability to interact productively with host major histocompatibility complex (MHC) molecules expressed on thymic epithelium. Cells with T-cell receptors specific for MHC class I shut off CD4 and commit to becoming cytotoxic cells, while cells with T-cell receptors for MHC class II shut off CD8 and become helper cells. We use gene targeting and transgenic technology in mice to study how the double-positive cells commit to either of the two major T-lymphocyte lineages.
In our studies with immunodeficiency viruses, we seek to understand how the interaction of viral envelope glycoproteins with CD4 and various chemokine receptors on the target cells results in membrane fusion and viral entry. We are also developing mouse model systems to determine how HIV infection causes loss of CD4+ helper T cells. In related studies, the functions of chemokine receptors in development and in inflammatory responses are being investigated.
Research KeywordsT-lymphocyte development and retroviral pathogenesis, cancer, immunology, metabolism, microbiology, microbiome, RNA biology, stem cell biology
Distinct Roles of Brd2 and Brd4 in Potentiating the Transcriptional Program for Th17 Cell Differentiation
Cheung, Ka Lung; Zhang, Fan; Jaganathan, Anbalagan; Sharma, Rajal; Zhang, Qiang; Konuma, Tsuyoshi; Shen, Tong; Lee, June-Yong; Ren, Chunyan; Chen, Chih-Hung; Lu, Geming; Olson, Matthew R; Zhang, Weijia; Kaplan, Mark H; Littman, Dan R; Walsh, Martin J; Xiong, Huabao; Zeng, Lei; Zhou, Ming-Ming. Distinct Roles of Brd2 and Brd4 in Potentiating the Transcriptional Program for Th17 Cell Differentiation. Molecular cell. 2017 Mar 3;65(6):1068-1080.e5 (2476932)
Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation
Karwacz, Katarzyna; Miraldi, Emily R; Pokrovskii, Maria; Madi, Asaf; Yosef, Nir; Wortman, Ivo; Chen, Xi; Watters, Aaron; Carriero, Nicholas; Awasthi, Amit; Regev, Aviv; Bonneau, Richard; Littman, Dan; Kuchroo, Vijay K. Critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation. Nature immunology. 2017 Feb 6;18(4):412-421 (2437332)
Disrupting Hepatocyte Cyp51 from Cholesterol Synthesis Leads to Progressive Liver Injury in the Developing Mouse and Decreases RORC Signalling
Urlep, Ziga; Lorbek, Gregor; Perse, Martina; Jeruc, Jera; Juvan, Peter; Matz-Soja, Madlen; Gebhardt, Rolf; Bjorkhem, Ingemar; Hall, Jason A; Bonneau, Richard; Littman, Dan R; Rozman, Damjana. Disrupting Hepatocyte Cyp51 from Cholesterol Synthesis Leads to Progressive Liver Injury in the Developing Mouse and Decreases RORC Signalling. Scientific reports. 2017 Jan 18;7:40775-40775 (2412972)
Short- and long-term effects of oral vancomycin on the human intestinal microbiota
Isaac, Sandrine; Scher, Jose U; Djukovic, Ana; Jimenez, Nuria; Littman, Dan R; Abramson, Steven B; Pamer, Eric G; Ubeda, Carles. Short- and long-term effects of oral vancomycin on the human intestinal microbiota. Journal of antimicrobial chemotherapy. 2017 Jan;72(1):128-136 (2274192)
miRNAs Are Essential for the Regulation of the PI3K/AKT/FOXO Pathway and Receptor Editing during B Cell Maturation
Coffre, Maryaline; Benhamou, David; Riess, David; Blumenberg, Lili; Snetkova, Valentina; Hines, Marcus J; Chakraborty, Tirtha; Bajwa, Sofia; Jensen, Kari; Chong, Mark M W; Getu, Lelise; Silverman, Gregg J; Blelloch, Robert; Littman, Dan R; Calado, Dinis; Melamed, Doron; Skok, Jane A; Rajewsky, Klaus; Koralov, Sergei B. miRNAs Are Essential for the Regulation of the PI3K/AKT/FOXO Pathway and Receptor Editing during B Cell Maturation. Cell reports. 2016 Nov 22;17(9):2271-2285 (2314502)