Lee Ratner, M.D., Ph.D.

Professor
Internal Medicine
Molecular Oncology
Molecular Microbiology
Pathology and Immunology

Molecular Microbiology and Microbial Pathogenesis Program
Molecular Genetics and Genomics Program

  • 314-362-8836

  • 314-362-8827

  • 314-362-8838

  • 314-747-2120

  • 8069

  • 562 McDonnell Medical Sciences Building

  • lratner@dom.wustl.edu

  • lymphocytes, virology, AIDS, leukemia, HIV, HTLV, NF kB

  • Molecular biology and pathogenesis of HIV and HTLV

Research Abstract:

My laboratory is involved in a molecular dissection of virus-cell interactions. We focus on two retroviurses: Human T-Cell Leukemia Virus Type 1 (HTLV-1) which causes a specific form of lymphoma, and Human Immunodeficiency Viruses (HIV) Types 1 and 2. Our studies of HTLV-1 are concerned with analysis of the mechanisms of leukemogenesis through studies of: transforming determinants in an infectious immortalizing HTLV-1 proviral clone; transgenic models utilizing the HTLV-1 trans-activator protein, which results in a lymphoproliferative malignancy; humanized mice; and identification and characterization of the receptor for the virus.

Our studies of HIV-1 focus on two distinct questions: 1) How does viral protein X (Vpx) enhance virus replication in quiescent cells? 2) How does the envelope glycoprotein interact with the receptor (CD4) and coreceptor (CXCR4 or CCR5) to allow virus entry? For these studies, we utilize infectious molecular clones of HIV-1 and HIV-2, cell culture and animal studies, small molecule and siRNA inhibitors, as well as viral and cellular cofactor mutants.

Information from these studies has been applied to developing novel therapeutic approaches for HTLV-1 and HIV-1 infections.

Selected Publications:

Cherian MA, Olson S, Cates K, Sundaramoorthi H, Cheng X, Harding J, Martens A, Challen GA, Tyagi M, Ratner L, Rauch D. 2018. An activating mutation of interferon regulatory factor 4, unique to adult T cell leukemia, J Biological Chemistry, 293:6844-6858, PMID:29540473.

Ratner L, Rauch D, Abel H, Caruso B, Baydoun HH, Noy A, Barta SK, Parekh S, Ramos JC, Ambinder R, Phillips A, Harding J, Cheng X, Jacobson S. 2016. Dose-adjusted EPOCH chemotherapy with bortezomib and raltegravir for human T-cell leukemia virus-associated T-cell leukemia lymphoma. Blood Cancer Journal, 6:e408, PMID:27015285

Zhang J, Gao X, Martin J, Rosa B, Chen Z, Mitreva M, Henrich T, Kuritzkes D, Ratner L. 2016. Evolution of coreceptor utilization to escape CCR5 antagonist therapy. Virology, 494:198-214, PMID:27128349

Cherian M, Baydoun H, Al-Saleem J, Kvaratskhelia M, Green P, Ratner L. 2015. Akt activation by human T-cell leukemia virus Tax oncoprotein. J Biological Chemistry, 290:26270-26281. PMID:26324707

Kyei GB, Cheng X, Ramani, R, Ratner L. 2015. Cyclin L2 is a critical HIV dependency factor in macrophages that controls SAMHD1 abundance. Cell Host Microbe, 17:98-106 , PMID: 25532805, PMCID: PMC4297224.

Baydoun HH, Cherian MA, Green PL, Ratner L. 2015. Inducible nitric oxide synthase mediates DNA double strand breaks in HTLV-1 induced leukemia/lymphoma Retrovirology, 12:71. PMID: 26265053, PMCID: PMC4534112

Rauch DA, Harding JC, Ratner L. 2014. IL-15 deficient Tax mice reveal a role for IL-1alpha in tumor immunity. PLOS One, 9:e85028, PMID: 24416335, PMCID: PMC3885672

Cheng X, Ratner L 2014. HIV-2 Vpx interacts with IRF5 inhibits its function. J Biological Chemistry, 289:9146-9157 PMID:24532789, PMCID: PMC3979364

Harmon B, Campbell N, Ratner L (2010). Role of Abl kinase and the Wave2 signaling complex in HIV-1 entry at a post-hemifusion step. PLOS Pathogens 6:e1000956.

Gross S, Rauch D, Harding J, Heinecke JW, Ratner L, Piwnica-Worms D (2009) Bioluminescence imaging of myeloperoxidase activity in vivo. Nature Med 15:455.

Last Updated: 7/27/2018 11:25:31 AM

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