Research Interests
Dr. Tsygankov’s research interests lie in the area of cell signaling, in particular, of its regulation by protein tyrosine kinases and phosphatases. Previous work of this laboratory with protein kinases of Src and Syk families and adaptor proteins of Cbl family, which is involved in Src- and Syk-mediated signaling, defined the novel protein family TULA. Dr. Tsygankov’s laboratory identified and characterized TULA, a Cbl-associated protein and later demonstrated that TULA-2, but not TULA, is an active protein tyrosine phosphatase capable of dephosphorylating Syk, which along with the highly-related kinase Zap-70 is a bona-fide substrate of TULA-2.
The current interests of Dr. Tsygankov are focused on understanding the role of TULA-family proteins in cell signaling and activation. This issue is addressed in two experimental systems – T lymphocytes and platelets. The results of the laboratory indicate that TULA- and TULA-2-null mice are significantly more responsive to experimentally induced colitis and that this inflammation to a large degree depends on hyper-responsiveness of TULA-deficient T cells to stimulation through T-cell antigen receptor. These results are directly related to understanding of molecular and cellular mechanisms of inflammatory bowel disease.
In collaboration with platelet experts, including Dr. Kunapuli from Temple University School of Medicine, Dr. Tsygankov’s group has also shown that TULA-2-mediated dephosphorylation of Syk significantly reduces platelet signaling mediated by GPVI collagen receptor, thus increasing the platelet activation threshold, which prevents unnecessary and potentially dangerous stimulation of platelet responses by sub-optimal stimuli. These results indicate that TULA-2-null platelet exhibit greatly potentiated responses in vitro and in vivo. Likewise, pharmacological inhibition of TULA-2 by a novel compound appears to exert similar effects on platelets. The current focus of Dr. Tsygankov’s laboratory in these studies is deciphering the molecular mechanism of down-regulatory functions of TULA-2 in GPVI signaling and assessing the therapeutic potential of TULA-2 as a target in treatment of platelet-dependent bleeding disorders.
Education, Training & Credentials
- Bach Institute of Biochemistry, Moscow