Glenn Dorsam

Associate Professor

Office: IACC 320

Office Phone: 701 231 5388

Lab: Loftsgard 210

Lab Phone: 701 231 7242

glenn.dorsam@ndsu.edu

Education

  • Ph.D. in Biochemistry from Virginia Commonwealth University (1998)

Professional Experience

  • Assistant Professor in the Department of Chemistry and Biochemistry (2004-2012)
  • Research Immunologist at the University of California, San Francisco (2002-2004)
  • NIH Postdoctoral Fellow athe University of California, San Francisco (2000-2002)
  • Postdoctoral Fellow at the University of California, San Francisco (1998-2000)

Research Interests

Research efforts in my laboratory are focused on two major fronts centered around the neuropeptide receptor, vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide receptor – 1 (VPAC1). First, we are interested in understanding the molecular mechanisms controlling the expression of VPAC1, a G protein coupled receptor (GPCR), in mammalian cells with an emphasis on the immune system. Recent studies in my laboratory have demonstrated that Src and JNK kinases, downstream of the T cell receptor (TCR), regulate the expression levels of VPAC1 at the mRNA and protein levels in murine CD4 T cells. The TCR is a unique receptor (antenna for cells) that can recognize foreign molecules expressed by invading organisms (example: bacteria and viruses) to alert the immune system to clear an infection. The above kinases are signaling enzymes that amplify this intracellular chemical message that promotes cellular division (called clonal selection) and generates the “cellular army” needed to clear the invading organism. Our studies show that VPAC1 is significantly downregulated during this process and suggests that its normal role is to keep immune cells in a quiescent, non-dividing state. Moreover, we have investigated whether subnuclear localization changes of the VPAC1 gene encoded in DNA is moved from a transcriptionally permissive to a transcriptionally refractory environment. A technique called chromatin immunoprecipitation (ChIP), which allows for a “snapshot” of protein/DNA interactions, revealed that the VPAC1 loci most likely remains in a transcriptionally permissive environment irrespective of signals emanating from the TCR. This indicates that the molecular mechanism governing its downregulation during TCR signaling and T cell proliferation is not due to a repositioning of the VPAC1 gene but rather direct suppressive effects in a transcriptionally permissive nuclear environment. Such mechanisms now being investigated are: i.) transcriptionally repressive epigenetic signals (methylation and/or acetylation of histone proteins part of chromatin), ii.) changes in stability of the VPAC1 mRNA message and iii.) trans-acting factors binding to cis-acting regulatory sequences in the VPAC1 promoter. Second, my research is interested in defining signal transduction cascades elicited by the VPAC1 receptor and how these intracellular chemical signals changes gene expression. To this end, we used murine CD4 T cells to identify global gene expression changes mediated by VPAC1 signaling. These data reveal important hypothetical molecular mechanisms that could explain well-known biology of VPAC1, including cellular homing of resting (non-dividing) T cells, and the differentiation of a suppressive T cell subtype called regulatory T cells. Current research is now ongoing to move both projects forward by validating our results in in vivo mouse models and utilizing human cellular samples. Preliminary discoveries have included fascinating possibilities regarding VPAC1 as a tumor suppressor in its ability to be silenced in human leukemia as well as its potential at regulating the biological activity of a master regulator and anti-leukemic factor, called Ikaros. Our laboratory is currently funded by the National Institutes of Health, and we work closely in collaboration with the Center of Protease Research and the Core Biology Facility at NDSU.

Most Recent Publications

  • Provost JJ, Rastedt D, Canine J, Ngyuen T, Haak A, Kutz C, Berthelsen N, Slusser A, Anderson K, Dorsam G, Wallert MA. (2012) Urokinase plasminogen activator receptor induced non-small cell lung cancer invasion and metastasis requires NHE1 transporter expression and transport activity. Cell Oncol (Dordr). Jan 31.
  • Hermann RJ, Van der Steen T, Vomhof-Dekrey EE, Al-Badrani S, Wanjara SB, Failing JJ, Haring JS, Dorsam GP. (2012) Characterization and use of a rabbit-anti-mouse VPAC1 antibody by flow cytometry. J Immunol Methods. Feb 28;376(1-2):20-31.
  • Vomhof-DeKrey, E.E., Sandy, A.R., Failing, J., Hermann, R.J., Hoselton, S., Schuh. J., Weldon, A, Payne, K, and Dorsam G. (2011) Radical Reversal Vasoactive Intestinal Peptide Receptors in Early Lymphopoiesis. (2011) Peptides. doi:10.1016/j.peptides.2011.08.014 epub ahead of print
  • G Dorsam, K Benton and S Batra. The Vasoactive Intestinal Peptide Signaling Axis in Human Leukemia. (2011) World Journal of Biological Chemistry. June26;2(6):146-60.
  • E. Vomhof-Dekrey, J. Haring and G. Dorsam. Vasoactive Intestinal Peptide Receptor 1 is Downregulated During Expansion of Antigen-Specific CD8 T Cells Following Primary and Secondary Listeria monocytogenes Infections. (2011) Journal of Neuroimmunology. May;234(1-2):40-8.
  • G Dorsam, S Hoselton, A Sandy, A Samarasinghe, E Vomhof-DeKrey, S Dorsam and J Schuh. Gene Expression Profiling and Network Analysis of Peripheral Blood Monocytes in a Chronic Model of Allergic Asthma. (2010) Microbiol Immunol. Sep;54(9):558-63.
  • S Dorsam, E Vomhof-DeKrey, R Hermann, J Haring, T Van der Steen, E Wilkerson, G Boskovic, J Denvir, Y Dementieva, D Primerano and G Dorsam. (2010) Identification of the Early VIP-Regulated Transcriptome and its Associated Interactome in Resting and Activated Murine CD4 T Cells. Mol Immunol. 2010 Mar; 47(6):1181-1194.
  • Benton KD, Hermann RJ, Van der Steen, Travis, Smith J, Dovat S, Dorsam G. (2009) Transcriptionally Permissive Epigenetic Landscape at the Vasoactive Intestinal Peptide Receptor-1 Promoter Suggests a Euchromatin Nuclear Positioning in Murine CD4 T Cells. Regulatory Peptides Nov 27; 158 (1-3): 68-76.