INDIVIDUAL RESEARCHER

Harold A. Singer , Ph.D.
Professor & Director
e-mail: singerh@mail.amc.edu

Education

1982 - Ph.D. from Dept. of Pharmacology, University of Virginia

Current Research

Research Interests: 1. intracellular signaling by protein kinases 2. structure/function of CaM kinase II isozymes 3. regulation of vascular smooth muscle cell contraction, migration and growth The principal objective of this laboratory is to define intracellular signaling pathways that mediate contractile and growth stimulus induced responses in vascular smooth muscle (VSM). This knowledge provides a basis for; a) understanding pathology underlying pervasive vascular diseases including hypertension, atherosclerosis, and injury-induced blood vessel occlusion resulting from VSM cell hyperplasia, and b) rational targeting of therapeutic agents aimed at controlling these disorders. Research is focused on two multifunctional protein kinase families, protein kinase C (PKC)and Ca²⁺/calmodulin-dependent protein kinase II (CaM kinase II). Our previous work implicated PKC as a regulator of VSM contractile activity, functioning in parallel to the established regulatory system involving myosin light chain kinase, which phosphorylates and activates the contractile protein myosin. Currently, we are exploring the functional significance of a physical interaction between a specific form of PKC (PKCdelta) and intracellular components of cell attachment (focal adhesion) complexes with respect to the control of VSM cell motility, gene expression and proliferative responses stimulated by injury and stretch. Ca²⁺ is an essential intracellular messenger in virtually all cells and participates in the control of numerous cellular functions, including muscle contraction. Our second major area of interest is to establish the role of CaM kinase II as a mediator of these intracellular Ca²⁺ signals. This laboratory has been instrumental in discovering new forms of CaM kinase II that are variably expressed in all cells. We have used this knowledge to develop molecular, immunological, and pharmacological approaches that we are applying to studies of CaM kinase II function in VSM. Our current goals are: 1) to define how CaM kinase II subunit/holoenzyme structure and autophosphorylation affects targeting of the kinase to specific cellular locations, 2) to determine the role of CaM kinase II as an intermediate in the activation of mitogen activated protein kinase (MAP kinase), another multifunctional protein kinase which is important in controlling patterns of gene expression and cell growth, and 3) to determine how CaM kinase II regulates contractile function in arterial smooth muscle.

Research

INDIVIDUAL RESEARCHER

Education

Current Research

References