Research Interests of Biochemistry Faculty
ROBERT P. CARTY
Associate Professor; Ph.D., SUNY Downstate Medical Center, 1963.
Theoretical calculations of protein conformation; enzyme mechanisms.
MARSHALL ELZINGA
Professor; Ph.D., University of Illinois at Urbana, 1964.
Role of cellular myosin in growth and differentiation of muscle and nerve cells. Organization of actin filaments. Biochemistry of Alzheimers Disease paired helical filaments.
MARIANO ESTEBAN
Professor; Ph.D. University of Santiago (Spain), 1970.
Molecular mechanisms of viral pathogenesis using vaccinia virus as model. Virus tropism and cell receptors. Gene expression/interferon action. Recombinant vaccines; B and T-cell responses to recombinant antigens. AIDS and leishmaniosis.
DAVID ESSEX
Assistant Professor of Medicine and Biochemistry; M.D. Rutgers Medical School, 19840.
Clinical and basic research in hemostasis, specifically: the role of platelet protein disulfide isomerase and thrombospondin in hemostasis, wound healing and atherosclerosis and other problems in the biochemistry of platelet function and cell adhesion.
Protein disulfide isomerase (PDI) catalyses the reversible formation as well as the isomerization of disulfide bonds. From its location in the endoplasmic reticulum, its broad substrate specificity and other experimental observations, PDI is generally considered to participate in the proper folding and disulfide bonding of nascent proteins. We reported that, upon activation, platelets release PDI activity into the medium. This was an interesting observation for two reasons. First, there are numerous possible physiological and pathological roles for PDI activity at the site of vessel injury, and, second, the absence of protein synthesis and of a traditional endoplasmic reticulum in platelets suggests a different function and a different location for platelet PDI. We purified PDI from platelets, and generated antibodies to establish a single PDI in platelets and that an immunologically identical protein was released upon platelet activation. PDI was localized to the platelet plasma membrane and found to be released from the membrane by vesiculation. This observation is important because PDI would be available at the site of vascular injury where it may modify the function of proteins by reduction or isomerization of disulfide bonds or covalently cross-link proteins within the extracellular matrix or to cell membranes.
Recent Publications:
1. Essex DW, Chen K, Swiatkowska M: Localization of protein disulfide isomerase to the external surface of the platelet plasma membrane. Blood 86:2168-2173, 1995
2. Chen K, Detwiler TC, Essex DW: Characterization of protein disulfide isomerase released from activated platelets. British Journal of Haematology, 90:425-431, 1995.
3. Chen K, Essex DW: Purification of secreted platelet protease nexin I. Thrombosis Research 79:527-529, 1995.
RICHARD D. FEINMAN
Professor, Ph.D.; University of Oregon, 1970.
Models of learning; Chemistry of proteolytic enzymes and inhibitors.
Feinman, R. (1994) The Proteinase Binding Reaction of Alpha2-Macroglobulin. Annals of the New York Academy of Sciences. 737, 245-266 (1994).
Abstract: A review of the reaction of the plasma inhibitor with proteinases.
MIRIAM H. FEUERMAN
Asssistant Professor; Ph.D., University of California, Irvine, 1986.
Regulation of gene expression during liver regeneration and tumorigenesis. Control of liver growth.
Lin, Y., Jin, D. K., Vacher, J. & Feuerman, M. H. (1995) Sequence Requirements for Alpha-fetoprotein gene expression during liver regeneration. Cell Growth and Differentiation, in press (Dec., 1995).
The alpha-fetoprotein (AFP) gene in the liver is expressed only in times of growth -- in the fetus, during liver regeneration or in tumorigenesis. To study the mechanism of induction of AFP gene expression during liver regeneration in the adult , we used transgenic mice and mapped the required cis-acting DNA sequences. Our data show that at least 2 segments of DNA are required for regulation in response to liver regeneration: a distal sequence between -838 and -1010 and a proximal sequence between -118 and the transcriptional start site.
GREGORY GICK
Associate Professor; Ph.D., Duke University, 1981. Molecular mechanisms of eukaryotic gene expression; the role of DNA sequence motifs and trans-acting factors in the regulation of mammalian Na,K-pump subunit genes.
ALAN R. GINTZLER
Professor; Ph.D., New York University Medical Center,1974. Opiate receptors and endorphins; physiological regulation of endogenous opioid systems; biochemical basis of narcotic addiction.
LEO KESNER
Professor Emeritus; Ph.D., SUNY, Downstate Medical Center, 1961. Proteases and cancer; protease inhibitors; nutrition; insulinase and its inhibitors; reactive oxygen and cellular damage.
LEON LERNER
Professor;-Ph.D., University of Illinois at the Medical Center, 1964. Carbohydrate Chemistry. Nucleic acid antimetabolites as anticancer and antimicrobial drugs. Design of nucleoside and nucleotide analogues as inhibitors of enzymes of nucleic acid metabolism.
MARY MAKOWSKE
Assistant Professor,; Ph.D., University of Michigan, 1983. Protein Kinase C isozymes in growth factor-mediated signal transduction and in cellular differentiation and transformation; phorbol ester-mediated gene expression.
JULIE I. RUSHBROOK
Associate Professor; Ph.D., Rutgers the State University of New Jersey, 1978. Biochemical changes associated with differentiation, development and disease; identification and structural characterization of affected proteins.
Recent PublicationZeng, Y. Weiss, C. Yao, T.-T. Huang, J., Siconolfi-Baez L., Hsu P. and Rushbrook J. I. (1995). Isocitrate dehydrogenase from bovine heart: primary structure of subunit 3/4. Biochemical Journal. 310: 507-516
Abstract:
Bovine NAD(+)-dependent isocitrate dehydrogenase was shown previously to contain four subunits of approx. 40 kDa (subunits 1-4) possessing different peptide maps and electrophoretic properties [Rushbrook and Harvey (1978) Biochemistry 17, 5339-5346]. In this study the heterogeneity is confirmed using enzyme purified by updated methods and from single animals, ruling out allelic variability. Subunits 1 and 2 were differentiated from each other and from subunits 3 and 4 by N-terminal amino acid sequencing. Subunits 3 and 4 (subunits 3/4) were identical in sequence over 30 residues. The N-terminal residues of subunits 1 and 2 were homologous but not identical with the beta- and gamma-subunits respectively of the comparable pig heart enzyme. Subunits 3/4 were identical over 30 residues with the N-terminus of the pig heart alpha-subunit. Full-length sequence, including that for mitochondrial import, is presented for a protein with the processed N-terminus of subunits 3/4, deduced from cloned cDNA obtained utilizing the N-terminal sequence information. The derived amino acid sequence for the mature protein contains 339 amino acids and has a molecular mass of 36,685 Da. Complete identity with N-terminal and Cys-containing peptides totalling 92 residues from the alpha-subunit of the pig heart enzyme [Huang and Colman (1990) Biochemistry 29, 8266-8273] suggests that maintenance of a particular three-dimensional structure in this subunit is crucial to the function of the enzyme. An electrophoretic heterogeneity within the pig heart alpha-subunit, similar to that shown by bovine subunits 3/4, was demonstrated. One reordering of the Cys-containing peptides of the pig heart alpha-subunit is indicated. Sequence comparison with the distantly related NADP(+)-dependent enzyme from Escherichia coli, for which the three-dimensional structure is known [Stoddard, Dean and Koshland (1993) Biochemistry 32, 9310-9316] shows strong conservation of residues binding isocitrate, Mg2+ and the NAD+ moiety of NADP+, consistent with a catalytic function.
ALFRED STRACHER
Professor; Ph.D., Columbia University,1956. Muscle and non-muscle motility; cytoskeleton structure and its interaction with membrane; molecular mechanism of neuromuscular degeneration; proteases and protease inhibitors.
DALTON WANG
Research Associate Professor; Ph.D., McGill University,1957. Protein chemistry; mechanism of protease and protease inhibitor interactions, chemosensory signal transduction.