Pharmacology and Toxicology

Benjamin Tourdot

Graduate Student
Department of Pharmacology and Toxicology

B.S., University of Wisconsin-Madison

Faculty Advisor:  Dr. Debra Newman
Email: btourdot@mcw.edu
Phone: (414) 937-3825

Research Interest

Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a glycoprotein constitutively expressed on the surfaces of endothelial cells, platelets, and subsets of leukocytes. PECAM-1 serves a variety of functions in vascular homeostasis, including inhibition of thrombosis and inflammation. PECAM-1 KO mice are more susceptible to noninfectious inflammatory stimuli than their WT counterparts due to a heightened inflammatory response that is characterized by increased cytokine production, leukocyte migration and vascular permeability. Whether the intensified immune response of PECAM-1 KO relative to WT mice could be beneficial to PECAM-1 KO mice challenged with an infectious stimulus, however, is not known. We hypothesize that, due to heightened immune responses, PECAM-1 KO mice will more rapidly resolve an acute infection than their WT counterparts. To test this hypothesis we are comparing the survival of PECAM-1 KO and WT mice challenged with either Sendai virus or colon ascends stent peritonitis, both of which are models of acute infection.

Our lab is also interested in how PECAM-1 inhibitory signaling is regulated. Many inhibitory functions of PECAM-1 depend on recruitment of the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase, SHP-2, which itself depends on phosphorylation of ITIMs (Immunoreceptor Tyrosine-based Inhibitory Motifs) within the PECAM-1 cytoplasmic domain. Phosphorylation of PECAM-1 ITIM tyrosine residues is mediated by non-receptor tyrosine kinases (NRTKs). Previous studies in our laboratory have provided evidence for sequential phosphorylation of PECAM-1 ITIMs, with Y₆₈₆ phosphorylation preceding that of Y₆₆₃. However, the mechanism underlying sequential phosphorylation of the PECAM-1 ITIMs remains unknown. My research currently focuses on using biochemical approaches to determine the mechanism underlying the sequential ITIM phosphorylation of PECAM-1. These studies will enable us to gain a better understanding of how PECAM-1 inhibitory signaling is regulated.

Publication

Privratsky JR, Tourdot BE, Newman DK, Newman PJ. The anti-inflammatory actions of PECAM-1 do not involve regulation of endothelial cell NFκB. J Immunol. 184(6):3157-63, 2010.

Research Interests:

Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a glycoprotein constitutively expressed on the surfaces of endothelial cells, platelets, and subsets of leukocytes. PECAM-1 serves a variety of functions in vascular homeostasis, including inhibition of thrombosis and inflammation. PECAM-1 KO mice are more susceptible to noninfectious inflammatory stimuli than their WT counterparts due to a heightened inflammatory response that is characterized by increased cytokine production, leukocyte migration and vascular permeability. Whether the intensified immune response of PECAM-1 KO relative to WT mice could be beneficial to PECAM-1 KO mice challenged with an infectious stimulus, however, is not known. We hypothesize that, due to heightened immune responses, PECAM-1 KO mice will more rapidly resolve an acute infection than their WT counterparts. To test this hypothesis we are comparing the survival of PECAM-1 KO and WT mice challenged with either Sendai virus or colon ascends stent peritonitis, both of which are models of acute infection.

Our lab is also interested in how PECAM-1 inhibitory signaling is regulated. Many inhibitory functions of PECAM-1 depend on recruitment of the Src homology 2 (SH2) domain-containing protein tyrosine phosphatase, SHP-2, which itself depends on phosphorylation of ITIMs (Immunoreceptor Tyrosine-based Inhibitory Motifs) within the PECAM-1 cytoplasmic domain. Phosphorylation of PECAM-1 ITIM tyrosine residues is mediated by non-receptor tyrosine kinases (NRTKs). Previous studies in our laboratory have provided evidence for sequential phosphorylation of PECAM-1 ITIMs, with Y₆₈₆ phosphorylation preceding that of Y₆₆₃. However, the mechanism underlying sequential phosphorylation of the PECAM-1 ITIMs remains unknown. My research currently focuses on using biochemical approaches to determine the mechanism underlying the sequential ITIM phosphorylation of PECAM-1. These studies will enable us to gain a better understanding of how PECAM-1 inhibitory signaling is regulated.

Publication:

Privratsky JR, Tourdot BE, Newman DK, Newman PJ. The anti-inflammatory actions of PECAM-1 do not involve regulation of endothelial cell NFκB. J Immunol. 184(6):3157-63, 2010.