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Thomas Jefferson University - Suresh K. Joseph, Ph.D.
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Suresh K. Joseph, Ph.D.
Pathology, Anatomy and Cell Biology
Thomas Jefferson University
Jefferson Medical College
Department of Pathology
Anatomy & Cell Biology
Professor
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Mailing Address
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1020 Locust Street
Philadelphia, Pennsylvania 19107
United States
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Expertise and Research Interests
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An elevation of the free calcium concentration in the cytoplasmic compartment is an integral component of the mechanism by which cells respond to many hormones, growth-factors and neurotransmitters. D- myo-Inositol 1,4,5-trisphosphate (IP3) is an intracellular messenger mediating the hormonal mobilization of Ca2+ from intracellular stores. This molecule interacts with a specific IP3 receptor ( IP3R ) that has been purified and shown to be a ligand-gated calcium channel. The work in my lab is focused on studying the structure, function and regulation of IP3 receptors.
The current projects in our lab include:
*Examining the gating mechanism by which IP3 binding leads to opening of the channel
*Identifying key residues in the ion conduction pore by mutagenesis
*Studying the molecular mechanism of the large structural changes in the receptor induced by calcium binding
*Investigating the role of the IP3R in apoptosis, particularly with reference to the finding that the channel is phosphorylated by Akt kinase.
*Studying the biosynthesis and degradation of IP3Rs. A major interest is the mechanism of agonist-mediated degradation which involves the ubiquitin/proteasome pathway.
The long-term goal is to understand how these proteins function in individual cells to generate complex spatial and temporal patterns in their Ca2+ transients and how such signals are decoded to alter physiological responses.
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Keywords
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Ankyrin; Calcium Binding Protein; Calcium Channel; Calcium Flux; Chimeric Protein; Clone Cell; Diabetes; Digestive Diseases And Disorders; Digestive System; Hormone Receptor; Hormone Regulation Control Mechanism; Inositol Phosphate; Kidney (Renal) Functions; Kidney Disease; Laboratory Rat; Phosphoprotein Phosphatase; Protein Isoform; Protein Kinase; Protein Structure Function; Receptor Binding; Receptor Expression; Recombinant Protein; Urology
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Publications
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- Lin C; Widjaja J; Joseph SK. The interaction of calmodulin with alternatively spliced isoforms of the type-I inositol trisphosphate receptor. Journal of Biological Chemistry. 275(4): 2305-11, 28 2000
- Bokkala S; Rubin E; Joseph SK. Effect of chronic ethanol exposure on inositol trisphosphate receptors in WB rat liver epithelial cells. Alcoholism, Clinical and Experimental Research. 23(12): 1875-83, Dec 1999
- Joseph SK; Boehning D; Bokkala S; Watkins R; Widjaja J. Biosynthesis of inositol trisphosphate receptors: selective association with the molecular chaperone calnexin. Biochemical Journal. 342 \( Pt 1\): 153-61, 15 Aug 1999
- Patel S, Joseph SK, Thomas AP. Molecular properties of inositol 1,4,5-trisphosphate receptors. Cell Calcium. 25(3): 247-64, Mar 1999
- Sharma K; Wang L; Zhu Y; DeGuzman A; Cao GY; Lynn RB; Joseph SK. Renal type I inositol 1,4,5-trisphosphate receptor is reduced in streptozotocin-induced diabetic rats and mice. American Journal of Physiology. 276(1 Pt 2): F54-61, Jan 1999
- Sharma K; Wang L; Zhu Y; Bokkala S; Joseph SK. Transforming growth factor-beta1 inhibits type I inositol 1,4,5-trisphosphate receptor expression and enhances its phosphorylation in mesangial cells. Journal of Biological Chemistry. 272(23): 14617-23, 6 1997
- Bokkala S, Joseph SK. Angiotensin II-induced down-regulation of inositol trisphosphate receptors in WB rat liver epithelial cells. Evidence for involvement of the proteasome pathway. Journal of Biological Chemistry. 272(19): 12454-61, May 1997
- Joseph SK, Boehning D, Pierson S, Nicchitta CV. Membrane insertion, glycosylation, and oligomerization of inositol trisphosphate receptors in a cell-free translation system. Journal of Biological Chemistry. 272(3): 1579-88, Jan 1997
- Rooney TA, Joseph SK, Queen C, Thomas AP. Cyclic GMP induces oscillatory calcium signals in rat hepatocytes. Journal of Biological Chemistry. 271(33): 19817-25, Aug 1996
- Joseph SK. The inositol triphosphate receptor family. Cellular Signalling. 8(1): 1-7, Jan 1996
- Renard-Rooney DC; Joseph SK; Seitz MB; Thomas AP. Effect of oxidized glutathione and temperature on inositol 1,4,5-trisphosphate binding in permeabilized hepatocytes. Biochemical Journal. 310 \( Pt 1\): 185-92, 15 1995
- Joseph SK; Ryan SV; Pierson S; Renard-Rooney D; Thomas AP. The effect of mersalyl on inositol trisphosphate receptor binding and ion channel function. Journal of Biological Chemistry. 270(8): 3588-93, 24 1995
- Joseph SK; Lin C; Pierson S; Thomas AP; Maranto AR. Heteroligomers of type-I and type-III inositol trisphosphate receptors in WB rat liver epithelial cells [published erratum appears in J Biol Chem 1996 Mar 29;271\(13\):7874. Journal of Biological Chemistry. 270(40): 23310-6, 6 Oct 1995
- Joseph SK, Pierson S, Samanta S. Trypsin digestion of the inositol trisphosphate receptor: implications for the conformation and domain organization of the protein. Biochemical Journal. 307 ( Pt 3): 859-65, May 1995
- Joseph SK. Biosynthesis of the inositol trisphosphate receptor in WB rat liver epithelial cells. Journal of Biological Chemistry. 269(8): 5673-9, 25 1994
- Hansen CA, Joseph SK, Robishaw JD. Ins 1,4,5-P3 and Ca2 signaling in quiescent neonatal cardiac myocytes. Biochimica Et Biophysica Acta. 1224(3): 517-26, Dec 1994
- Joseph SK, Esch T, Bonner WD Jr. Hydrolysis of inositol phosphates by plant cell extracts. Biochemical Journal. 264(3): 851-6, Dec 1989
- Joseph SK, Hansen CA, Williamson JR. Inositol tetrakisphosphate mobilizes calcium from cerebellum microsomes. Molecular Pharmacology. 36(3): 391-7, Sep 1989
- Joseph SK, Williamson JR. Inositol polyphosphates and intracellular calcium release. Archives of Biochemistry and Biophysics. 273(1): 1-15, Aug 1989
- Joseph SK, Rice HL. The relationship between inositol trisphosphate receptor density and calcium release in brain microsomes. Molecular Pharmacology. 35(3): 355-9, Mar 1989
- Joseph SK, Rice HL, Williamson JR. The effect of external calcium and pH on inositol trisphosphate-mediated calcium release from cerebellum microsomal fractions. Biochemical Journal. 258(1): 261-5, Feb 1989
- Joseph SK, Rice HL, Nicchitta CV. Characteristics of GTP-mediated microsomal Ca2 release. Biochimica Et Biophysica Acta. 945(2): 185-94, Nov 1988
- Supattapone S, Danoff SK, Theibert A, Joseph SK, Steiner J, Snyder SH. Cyclic AMP-dependent phosphorylation of a brain inositol trisphosphate receptor decreases its release of calcium. Proceedings of the National Academy of Sciences (USA). 85(22): 8747-50, Nov 1988
- Nicchitta CV, Joseph SK, Williamson JR. GTP-mediated Ca2 release in rough endoplasmic reticulum. Correlation with a GTP-sensitive increase in membrane permeability. Biochemical Journal. 248(3): 741-7, Dec 1987
- Joseph SK, Hansen CA, Williamson JR. Inositol 1,3,4,5-tetrakisphosphate increases the duration of the inositol 1,4,5-trisphosphate-mediated Ca2 transient. Febs Letters. 219(1): 125-9, Jul 1987
- Joseph SK, Williamson JR. Characteristics of inositol trisphosphate-mediated Ca2 release from permeabilized hepatocytes. Journal of Biological Chemistry. 261(31): 14658-64, Nov 1986
- Prentki M, Deeney JT, Matschinsky FM, Joseph SK. Neomycin: a specific drug to study the inositol-phospholipid signalling system?. Febs Letters. 197(1-2): 285-8, Mar 1986
- Brass LF, Joseph SK. A role for inositol triphosphate in intracellular Ca2 mobilization and granule secretion in platelets. Journal of Biological Chemistry. 260(28): 15172-9, Dec 1985
- Busa WB, Ferguson JE, Joseph SK, Williamson JR, Nuccitelli R. Activation of frog (Xenopus laevis) eggs by inositol trisphosphate. I. Characterization of Ca2 release from intracellular stores. Journal of Cell Biology. 101(2): 677-82, Aug 1985
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Individual Expertise profile of
Suresh K. Joseph, Ph.D., Copyright © Suresh K. Joseph, Ph.D..
Last Updated
by Admin
: Tuesday, December 30, 2008 12:15:10 PM
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