The Bohjanen Lab

Paul R. Bohjanen M.D., Ph.D.
Co-Director, Center for Infectious
Diseases and Microbiology Translational Research
  Associate Professor
Department of Microbiology
Department of Medicine
Center for Immunology
email: - bohja001@umn.edu
Office
address:

Center for Infectious Diseases and Microbiology Translational Research
3-124 McGuire Translational Research Facility
2001 6th St SE
Minneapolis, MN 55455

 
Office phone:
Lab phone:
Fax:
612-625-7679
612-624-0469
612-626-0623 		 

 

Research Interests

1.
T Lymphocyte mRNA Stability
Access our mRna Decay Database
2.
HIV Immune Reconstitution Inflammatory Syndrome

 

Current Lab Members

 

T Lymphocyte mRNA Stability

Research in my laboratory focuses on the role of mRNA decay in regulating T lymphocyte activation and function. Many genes that are important for cell growth and immune function are turned on at precise times and turned off at precise times. Dysregulated expression of many of these genes, including proto-oncogenes and cytokine genes, occurs in disease states such as cancer, autoimmunity, or immunodeficiency. One mechanism that cells use to turn off gene expression is specific degradation of mRNA within the cytoplasm. We have recently shown that the rate of decay of many transcripts encoding important regulatory proteins changes upon cellular activation, and these changes in mRNA decay can have dramatic effects on overall gene expression. Our goal is to understand the biochemical mechanisms that regulate mRNA decay and to understand the role of mRNA decay in regulating gene expression in disease states such as malignancy or virus infection.

 

Related Publications:

I. A. Vlasova, N. M. Tahoe, D. Fan, O. Larsson, J. Vasdewani, G. Karypis, C. S. Reilly, P. Bitterman, and P. R. Bohjanen.  2007.
Conserved GU-rich elements mediate mRNA decay by binding to CUG-binding protein 1.
Submitted.

H. H. Hau, R. Walsh, R.L. Ogilvie, C.S. Reilly, and P.R. Bohjanen.  2007.
Tristetraprolin recruits functional mRNA decay complexes to ARE sequences. 
J. Cell. Biochem.  100:1477-92.

R. R. Graham, C. Kyogoku, S. Siggurdson, I. A.Vlasova, L. Davies, E. C. Baechler, R. M. Plenge, T. Koeuth, W. A. Ortmann, G. Hom, J. Bauer, C. Gillett, N. Burtt, D. S. Cunninghame-Graham, M. Petri, I. Gunnarsson, E. Svenungsson,L. Rönnblom, G. Nordmark, P. K. Gregersen, K. Moser, P. Gaffney, L. A. Criswell, T. J. Vyse, A. C. Syvänen, P. R. Bohjanen, M. J. Daly, D. Altshuler, and T. W. Behrens.  2007.
Three functional variants of interferon regulatory factor 5 (IRF5) define risk and protective haplotypes for human SLE. 
Proc. Natl. Acad. Sci. USA 104:6758-63.

J.A. Smith, S.C. Schmechel, A. Raghavan, M. Abelson, C. Reilly, M.G. Katze, R.J. Kaufman, P.R. Bohjanen, and L.A. Schiff.  2006. 
Reovirus infection induces and benefits from an integrated cellular stress response. 
J. Virol.  80:2019-33.

C. Reilly, A. Raghavan, and  P. Bohjanen.  2006.
Global assessment of cross-hybridization for oligonucleotide arrays. 
J. Biomol. Tech.  17:163-172.

I. Vlasova, J. McNabb, A. Raghavan, D. Williams, C. Reilly, K.A. Bohjanen, and P.R.  Bohjanen.  2005.
Coordinate stabilization of growth-regulatory transcripts in T cell malignancies. 
Genomics. 86:159-171.

R. L. Ogilvie, M. Abelson, H. H. Hau,I. Vlasova,P. J. Blackshear, and P. R. Bohjanen. 2005.
Tristetraprolin Down-Regulates Interleukin-2 Gene Expression through AU-rich Element-Mediated mRNA Decay. 
J. Immunol.  174:953-961.

A. Raghavan and P.R. Bohjanen.  2004. 
Microarray-based analyses of mRNA decay in the regulation of mammalian gene expression. 
Briefings in Functional Genomics and Proteomics.  3:112-124.

A. Raghavan, M. Dhalla, T. Bakheet, R. L. Ogilvie, I. A. Vlasova, K. S. A. Khabar, B. R.G. Williams, and P. R. Bohjanen.  2004. 
Patterns of Coordinate Down-regulation of ARE-containing Transcripts following Immune Cell Activation. 
Genomics. 84:  1002-1013.

A. Raghavan, R.L. Ogilvie, C. Reilly,  M.L. Abelson, S. Raghavan, J. Vasdewani, M. Krathwohl, and P.R. Bohjanen.  2002. 
Genome-wide Analysis of mRNA Decay in Resting and Activated Primary Human T Lymphocytes.
Nucleic Acids Res.  30:5529-5538.

A. Raghavan, R.L. Robison, J. McNabb, C.R. Miller, D.A. Williams, and P.R. Bohjanen.  2001.
HuA and tristetraprolin are induced following T cell activation and display distinct but overlapping RNA-binding specificities. 
J. Biol. Chem.  276:47958-47965.

 

 

HIV Immune Reconstitution Inflammatory Syndrome

We are applying our expertise in immune cell gene expression and microarray technology to HIV immune reconstitution inflammatory syndrome (IRIS), an important complication of antiretroviral therapy (ART) that has recently emerged in Africa. (IRIS) is a paradoxical inflammatory response that occurs after initiating HIV antiretroviral therapy (ART).  Common IRIS scenarios include the “unmasking” of an occult opportunistic infection or the “paradoxical” symptomatic worsening of a prior infection despite microbiologic treatment success. We have developed a collaborative project with the Infectious Diseases Institute at Makerere University in Kampala, Uganda to prospectively follow HIV-infected patients in Uganda 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.

 

Related Publications:

D.R. Boulware and P.R. Bohjanen.  2007.  Chapter 18: 
HIV Immune Reconstitution Inflammatory Syndrome. In: Global HIV/AIDS Medicine.
M. Sande, P. Volberding, J. Lange, and W. Greene, Eds. 
Elsevier, Philadelphia.  pp. 193-205.

J. Baker, D. Boulware, and P.R. Bohjanen.  2006.
A Case For Treating High Hepatitis B DNA Levels Prior to Starting HIV Therapy. 
AIDS 20:2402-3.

P.R. Bohjanen and M.A. Sande.  2005. 
HIV immune reconstitution syndrome:  An emerging problem in resource-poor regions. 
Contagion.  2: 117-119.

P. Bohjanen and M. Sadigh. 2004.
Chapter 2, Basic Immunology, pp 23-33, in HIV/AIDS Training Program for Medical Doctors in Africa,
M. Kamya and M. Scheld, Eds., Makerere University, Kampala, Uganda.

P. Bohjanen and G. Taylor.  2004. 
Chapter 5, Antiretroviral Therapy and Management: Drug Toxicities, pp 388-397, in HIV/AIDS Training Program for Medical Doctors in Africa,
M. Kamya and M. Scheld, Eds., Makerere University, Kampala, Uganda.

P.R. Bohjanen, M.D. Johnson, L.A. Szczech, D.W. Wray, W.P. Petros, C.R. Miller, and C.B. Hicks.  2002. 
Steady state pharmacokinetics of lamivudine in HIV-infected patients with end-stage renal disease. 
Antimicrob. Agents Chemother.  46:2387-2392.