Department of Pathology and Laboratory Medicine Spring 2015 Seminar Series: Friday, February 6,
B. S. Nikolajczyk, PhD
Associate Professor of Medicine and Microbiology
B.S. The Ohio State University, Columbus, Ohio
Ph.D. The University of North Carolina at Chapel Hill
My lab is interested in understanding inflammation in type 2 diabetes and inflammatory bowel disease patients. Inflammation is strongly implicated in the most dire complications of type 2 diabetes, including cardiovascular disease and stroke. We are focusing on two cell types that promote inflammation in these patients: monocytes and B cells. Monocytes are well known to produce significant amounts of pro-inflammatory cytokines. We are specifically interested in how IL-1 beta, a cytokine at the apex of multiple pro-inflammatory cascades, is hyper-expressed by monocytes from type 2 diabetics. We have defined a “poised promoter architecture” for the IL-1 beta locus in normal monocytes. This structure is characterized by a constitutively accessible promoter and constitutive transcription factor association. Current work is aimed at understanding how this structure is changed in patients to result in IL-1 beta hyper-production. A second focus of the lab is to understand how B cells contribute to type 2 diabetes and inflammatory bowel disease through production of pro-inflammatory cytokines. We have found B cells in type 2 diabetes patients are fundamentally altered such that they unexpectedly respond to inflammatory stimuli. Ongoing analyses are characterizing these responses as well as the underlying molecular mechanisms driving them. These studies are aimed at identifying targets for alleviating the over-production of pro-inflammatory cytokines generally associated with the devastating complications of systemic inflammatory diseases.
- Nikolajczyk, BS, Cortes, M, Feinman, and R, Sen, R. 1997. Combinatorial Determinants of Tissue-Specific Transcription in B Cells and Macrophages. Mol. Cell Biol. 17:3527-3535
- Nikolajczyk, BS, and Sen, R. 1999 Stereochemical Considerations of Immunoglobulin Heavy Chain Enhancer Activation. In The Biology-Chemistry Interface. Marcel Dekker Inc., New York.
- Nikolajczyk, BS, Sanchez, JA, and Sen, R. 1999. ETS-protein dependent accessibility changes at the immunoglobulin m heavy chain enhancer. Immunity 11:11-20.
- Nikolajczyk, BS, Dang W, and Sen, R. 1999. Mechanisms of mu enhancer regulation in B lymphocytes. Cold Spring Harb. Symp. Quant. Biol. 64:99-107.
- Lewis R.T., Andreucci, A. and Nikolajczyk, B.S. 2001. PU.1-mediated transcription is enhanced by HMG-I(Y)-dependent structural mechanisms. J. Biol. Chem. 276:9550-9557.
- Andreucci,A., Reeves,R., McCarthy,K.M. and Nikolajczyk, B.S. 2002. Dominant-negative HMGA1 blocks mu enhancer activation through a novel mechanism. Biochem. Biophy.Res.Comm. 292:427-433.
- McCarthy, K.M., McDevit, D.C., Andreucci, A., Reeves, Raymond, and Nikolajczyk, B.S. 2003. HMGA1 co-activates transcription in B cells through indirect association with DNA. J. Biol. Chem. 278:42106-42114.
- Marecki, S., McCarthy, K.M., and Nikolajczyk, B.S. 2004. PU.1 as a chromatin accessibility factor for immune system genes. Mol. Immunol. 40:723-731.
- McDevit, D., Perkins, L., Atchison, M.A. and Nikolajczyk, B.S. 2005. The Igk3’ enhancer is activated by gradients of chromatin accessibility and protein association. J. Immunol. 174:2834-2842.
- Liang, M.D, Zhang, Y., McDevit, D., Marecki, S, and Nikolajczyk, B. 2006. The IL-1beta gene is transcribed from a poised promoter architecture in monocytes.
J Biol Chem. 2006 Jan 26; [Epub ahead of print]
- McDevit, D.C., and Nikolajczyk, B.S. 2006. Changes in immunoglobulin-nucleoprotein complex structure mapped by chromatin immunoprecipitation. Mol Immunol. 43(10):1541-1548.
- Liang, M.D., Y. Zhang, D. McDevit, S. Marecki, and B.S. Nikolajczyk. 2006. The Interleukin-1beta Gene is Transcribed from a Poised Promoter Architecture in Monocytes. J. Biol. Chem. 281:9227-9237.
- Nikolajczyk, B. 2006. Regulation of Cytokine Transcription in the Context of Chromatin. Arch. Immunol. 54:299-305.
- Nikolajczyk, B.S., S.H. Sardi, J.R. Tumang, and L.M. Ganley-Leal. 2007. Immunoglobulin Kappa Enhancers are Differentially Regulated at the Level of Chromatin Structure. Mol. Immunol. Mar 21; [Epub ahead of print]
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