Expertise

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. The focus of my research is to investigate the molecular mechanisms governing Ikaros-mediated transcriptional regulation of vasoactive intestinal peptide receptor - 1 (VPACR-1) in T lymphocytes.

Past Affiliations

Adjunct Faculty, Department of Chemistry and Biochemistry, College of Science and Mathematics, North Dakota State University

Assistant Research Immunologist, Allergy and Infectious Disease

Visiting Fellow, Allergy and Infectious Disease

Visiting Fellow, Allergy and Infectious Disease

Graduate Student, Biochemistry

Technician, Oral Biology

Assistant Professor, Department of Veterinary and Microbiological Sciences, College of Agriculture, Food Systems, and Natural Resources, North Dakota State University

Assistant Professor, Department of Chemistry and Biochemistry, College of Science and Mathematics, North Dakota State University

Communities
Molecular Biology, Veterinary Medicine, Veterinary Microbiology, Microbiology, Biochemistry, Molecular Biology, Cellular Biochemistry, Molecular Biochemistry, Agriculture
Degrees
PhD, Virginia Commonwealth University, Biochemistry, 1998
BS, Michigan State University, Biochemistry, 1990
Keywords
immunology cancer or carcinogenesis leukemia hematology molecular biology transcription chemical sciences biochemistry
Languages
English
Honors

Young Investigator Award (Neuropeptide Research), Twenty-third Annual Winter Neuropeptide Conference

Associations
American Association for Cancer Research
American Association of Immunologists
American Chemical Society
American Society for Biochemistry and Molecular Biology