MICaB Graduate Program
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Paul R. Bohjanen, M.D., Ph.D.
Director, Center for Infectious Diseases and Microbiology Translational Research
Director, Division of Infectious Diseases and International Medicine
Department of Microbiology and Immunology
Department of Medicine
University of Michigan, 1993, M.D., Ph.D
612-625-7679 - office
612-624-0469 - lab
T Lymphocyte mRNA Stability
My laboratory studies the role of mRNA decay in regulating T lymphocyte gene expression. We have discovered a novel mRNA degradation pathway regulated by the RNA-binding protein CELF1 and its binding site on mRNA known as the GU-rich element (GRE). This pathway coordinately regulates the expression of transcripts that encode regulators of cell growth and apoptosis. Our goal is to understand the biochemical mechanisms that regulate mRNA decay during T lymphocyte activation and disease states such as malignancy or virus infection.
HIV Immune Reconstitution Inflammatory Syndrome
We are applying our expertise in immune cell gene expression to HIV immune reconstitution inflammatory syndrome (IRIS), an important complication of antiretroviral therapy (ART) that is common in patients with advanced AIDS in Africa. IRIS is a severe and sometimes fatal paradoxical inflammatory response that occurs in AIDS patients as the immune system improves following initiation of ART. We are collaborating with the Infectious Diseases Institute at Makerere University in Kampala, Uganda to prospectively follow HIV-infected patients after they initiate antiretroviral therapy and to compare immune activation using microarrays, cytokine profiling, and flow cytometry in patients that do or do not develop IRIS. These studies will identify biomarkers that can be used to diagnose, predict, or monitor IRIS and will provide insight into the pathophysiology of IRIS that will allow the development of better treatments.
Bohjanen Lab Site
Selected Recent Publications:
- I. Vlasova-St. Louis, A.M. Dickson, P.R. Bohjanen, and C.J. Wilusz. 2013. CELFish ways to modulate mRNA decay. Biochim Biophys Acta-Gene Regul Mech. 1829:695-707.
- D. L. Wiesner, O. Moskalenko, J. M. Corcoran, T. McDonald, M. A. Rolfes, D. B. Meya, H. Kajumbula, A. Kambugu, P. R. Bohjanen, J. F. Knight, D. R. Boulware, and K. Nielsen. 2012. Cryptococcal Genotype Influences Immunologic Response and Human Clinical Outcome after Meningitis. mBio 3: e00196-12.
- D. Beisang, B. Rattenbacher, I.A. Vlasova-St. Louis, P.R. Bohjanen. 2012. Regulation of CUG-binding Protein 1 (CUGBP1) Binding to Target Transcripts upon T Cell Activation. J Biol Chem. 287: 950–960.
- I. A. Vlasova-St. Louis and P. R. Bohjanen. 2011. Coordinate Regulation of mRNA Decay Networks by GU-rich Elements and CELF1. Curr Opin Genet Dev. 21:444-51.
- D. R. Boulware, S.C. Bonham, D.B. Meya, D.L. Wiesner, G.S. Park, A, Kambugu, E.N. Janoff, P.R. Bohjanen. 2010. Paucity of initial cerebrospinal fluid inflammation in cryptococcal meningitis is associated with subsequent immune reconstitution inflammatory syndrome. J Infect Dis. 202:962-70.
- D. R. Boulware, D. B. Meya, T. L. Bergemann, D. Williams, I. A. Vlasova-St. Louis, J. Rhein, J. Staddon, A. Kambugu, E. N. Janoff, and P. R. Bohjanen. 2010. Antiretroviral therapy down-regulates innate antiviral response genes in patients with AIDS in sub-Saharan Africa. J Acquir Immune Defic Syndr. 55:428-38.
- D. R. Boulware, D. B. Meya, T. L. Bergemann, D. L Wiesner, J. Rhein, A. Musubire, S. J. Lee, A. Kambugu, E. N. Janoff, and P. R. Bohjanen. 2010. Clinical Features and Serum Biomarkers in HIV Immune Reconstitution Inflammatory Syndrome after Cryptococcal Meningitis: A Prospective Cohort Study. PLoS Med. 7:e1000384.
- B. Rattenbacher, D. Beisang, J. C. Jeschke, I. A. Vlasova-St. Louis, and P.R. Bohjanen. 2010. Analysis of CUGBP1 targets identifies GU-repeat sequences that mediate rapid mRNA decay. Mol. Cell Biol. 30:3970-80.
- R. L. Ogilvie, J. R. SternJohn, B. Rattenbacher, I. A. Vlasova, D. A. Williams, H. H. Hau, P. J. Blackshear, and P.R. Bohjanen. 2009. Tristetraprolin mediates interferon-gamma mRNA decay. J. Biol. Chem. 84:11216-11223.
- I. A. Vlasova, N. M. Tahoe, D. Fan, O. Larsson, B. Rattenbacher, J. R. SternJohn, J. Vasdewani, G.Karypis, C. S. Reilly, P. Bitterman, and P.R. Bohjanen. 2008. Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1. Mol. Cell. 29:263-70.