Principal Investigator Research Interests

Research Interests of CVID Faculty

	Toni Antalis Ph.D. Research in my laboratory is focused on the functions of proteases, the powerful hydrolytic enzymes that regulate the activities of many cellular proteins in vascular biology, angiogenesis and cancer. Specifically, we aim to understand how membrane serine proteases and their inhibitors contribute to cell survival, differentiation and malignant transformation. This work will provide insight into basic mechanisms of cell behavior, and enable the development of new targets for therapeutic interventions. Faculty Profile Research Staff

	Alexy Belkin Ph.D. My laboratory investigates the interactions of cells with the extracellular matrix. A major goal is to characterize the role of newly identified integrin-associated adhesion receptor, tissue transglutaminase (tTG), in cell migration, signaling and other adhesion-dependent processes. In turn, this work will elucidate a contribution of this protein to important human pathologies, including inflammatory and vasculoproliferative disorders and tumor metastasis. Faculty Profile

	Greg Carey Ph.D. Research in my laboratory is focused on understanding the mechanisms of action of anticancer agents, and is exploring the roles of receptor-stimulated reactive oxygen species in determining the fates of B-cells and lymphomas. Understanding this will help to design interventions to either protect helpful immune cells from unintended death (alleviating immunodeficiency), or to provoke carefully-controlled death of lymphomas. Faculty Profile

	Svetlana Chapoval M.D., Ph.D. My research is focused on immune semaphorins Sema4A and Sema4D. We will identify the cellular source of immune semaphorins and their receptors in the lung and define their precise roles in allergic airway inflammation in order to use them as novel targets for asthma therapy. Faculty Profile

	Nancy Fossett Ph.D. Hematopoiesis is coordinated by key regulatory molecules that drive lineage-specific developmental programs. Current models depict lineage commitment as a process that involves cross-antagonism between blood cell programs, which promotes one lineage at the expense of the others. The long-term goal of my laboratory is to better define the molecular genetic strategies that regulate hematopoiesis. This goal is accomplished by studying how evolutionarily conserved factors regulate blood and heart cell development in the fruit fly, Drosophila melanogaster. Faculty Profile

	Galina Hayes Ph.D. Faculty Profile

	Achsah Keegan Ph.D. Research in my laboratory is focused on signaling by the cytokines IL-4 and IL-13. These cytokines regulate many functions including protection from apoptosis, regulation of allergy and asthma, and the control of myeloid development and function. This work will provide insight into better therapies for asthma, inflammation, and for certain cancers. Faculty Profile Research Staff

	Leonid Medved Ph.D. My Laboratory is focused on the structure and interactions of fibrin(ogen). Specifically, we aim to complete the high resolution structure of the fibrinogen molecule and establish molecular mechanisms of its interaction with Lipoprotein(a), endothelial cells and leukocytes. This work will provide insight into the role of fibrin(ogen) in such important physiological and pathological processes as inflammation, angiogenesis and atherogenesis. Faculty Profile Research Staff

	Irina Mikhailenko Ph.D. Faculty Profile

	Sarah J Netzel-Arnett Ph.D. Targeting Serine Proteases for Ovarian Cancer Therapy Ovarian cancer is one of the most lethal female malignancies in the USA. Despite significant improvements in chemotherapy over the past decade, the long term survival of women with advanced ovarian cancer is poor, largely because the rates of disease recurrence are high. The underlying causes of ovarian cancers are little understood despite intensive study, and treatment options for patients with advanced disease are still inadequate. Membrane-anchored serine proteases are overexpressed by metastatic ovarian carcinomas and may contribute to cellular processes that drive advanced disease. In this research project, we propose to determine whether functional inhibition of these proteases impairs ovarian tumor growth and progression, and whether such inhibition can be exploited for new targeted drug therapies. Faculty Profile

	Sripriya Ranganathan Ph.D. Faculty Profile

	David Scott Ph.D. The Scott laboratory has been using gene therapy approaches to induce tolerance for undesirable immune responses, such as in autoimmunity and hemophilia. The approach is to express the targeted proteins (antigens) in a given disease as a fusion with an antibody molecule in white blood cells, called B lymphocytes, which present and produce these "fusion Igs" to tolerize the immune system. This system has been successful in four autoimmune disease models and in hemophilia. The laboratory is exploring the role of regulatory T cells in this model, and beginning to apply it in non-human primates, with a possible extension into the prevention of transplant rejection. Research Profile

	Dudley Strickland Ph.D. Work in my laboratory focuses on inflammatory events that contribute to the progression of diseases such as atherosclerosis. Key modulators of these processes are low density lipoprotein (LDL) receptor family members. One member of this family, the LDL receptor-related protein (LRP) is a large cellular receptor that not only functions as an important cargo transporter, but also informs the cell of changes in its environment by mediating signaling responses. A goal of these studies is to understand the role of LRP and other LDL receptor family members in modulating cell signaling events and how this affects development of certain diseases, such as atherosclerosis and Alzheimers disease.Faculty Profile Research Staff

	Mark Williams Ph.D. The major focus of research in the Williams laboratory is to investigate the mechanisms by which reactive oxygen or nitrogen species affect the immune system. Results from the laboratory have demonstrated that endogenous reactive species are produced upon T cell receptor (TcR) or Fas stimulation in cultured and primary T cells. Overexpression of specific antioxidant enzymes (catalase and superoxide dismutase) has been used to define the reactive oxygen species (ROS) produced upon receptor stimulation and is being used to define their biologic role(s) and the molecular targets of receptor stimulated ROS generation. This production of ROS has been shown to regulate TcR-stimulated signal transduction including activation of MAPK and expression of FasL.Faculty Profile Research Staff

	Jeff Winkles Ph.D. Research in my laboratory is focused on the biology of a cytokine named TWEAK and its cell surface receptor named Fn14, with particular emphasis on the role of this ligand-receptor pair in cancer. We have found that TWEAK is expressed in tumors and that it can induce blood vessel formation (angiogenesis) in vivo, so one of our projects is focused on determining whether this cytokine could play a role in the process of tumor neovascularization, which is required for tumor growth and metastasis. Also, since our laboratory and others have reported that Fn14 is overexpressed in several tumor types and that Fn14 levels may influence tumor cell migration, a second project is focused on the role of Fn14 in cell invasion, an essential step in the metastatic cascade. Taken together, these studies will provide insight into whether TWEAK and/or Fn14 are potential molecular targets for cancer therapy. Faculty Profile Research Staff

	Sergiy Yakovlev Ph.D. Faculty Profile

	Steve Zhan Ph.D. My laboratory has been investigating the molecular mechanism of tumor cell invasion by focusing on the regulation of actin polymerization, the driving force that facilitates the formation of membrane protrusions and the penetration of tumor cells into extracellular matrix. In particular, we have studied cortactin, a gene that plays a critical role in regulating the assembly of actin filaments at the foci of cellular protrusions. We showed that overexpression of cortactin, enhances metastasis and more recently that cortactin regulates cell motility and invasion by promoting membrane remodeling as well as intracellular trafficking of internalized receptors. This work has led us to investigate the mechanisms that regulate the function of cortactin by the oncogene Src and on a recently discovered cortactin binding protein called missing in metastasis (MIM). We aim to reveal the physiological and pathological role of MIM in cells and its role in tumor cell invasion. Faculty Profile

	Li Zhang Ph.D. Stem cells possess the ability to self-renew and to differentiate into multiple tissue types, and thus are ideal source of cells for tissue repair and regeneration. However, successful stem cell-based tissue regeneration depends on our ability to prepare a homogenous stem cell population and to overcome tissue rejection mediated by host immune cells. My research program comprises two separate projects: one is focused on the roles of mesenchymal stem cells in tissue repair/regeneration and the other is to study the roles of leukocytes in physiological processes such as innate and adaptive immune responses, and in development of such diseases as: atherosclerosis, myocardial infarction, stroke, and osteoporosis. Faculty Profile

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