Philadelphia University + Thomas Jefferson University

Joseph, Suresh K.

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Suresh K. Joseph, PhD

Contact Dr. Joseph

1020 Locust Street
Jefferson Alumni Hall, Suite 230
Philadelphia, PA 19107

(215) 503-1221

Medical School

PhD, University of Bristol, England - 1978

University Appointment

Professor, Department of Pathology, Anatomy & Cell Biology

Research and Clinical Interests

Structure, function, and regulation of the inositol trisphosphate receptor (IP3R); biosynthesis and assembly of IP3R homo- and heteroligomers; mechanisms of proteosomal and lysosomal degradation of IP3R.

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.

Publications

Most Recent Peer-Reviewed Publications

  1. Isoform- and species-specific control of inositol 1,4,5-trisphosphate (IP3) receptors by reactive oxygen species
  2. Hormone-Induced Calcium Oscillations Depend on Cross-Coupling with Inositol 1,4,5-Trisphosphate Oscillations
  3. Functional inositol 1,4,5-trisphosphate receptors assembled from concatenated homo- and heteromeric subunits
  4. Identification of functionally critical residues in the channel domain of inositol trisphosphate receptors
  5. Guidelines for the use and interpretation of assays for monitoring autophagy
  6. S-glutathionylation activates STIM1 and alters mitochondrial homeostasis
  7. Calcium-dependent conformational changes in inositol trisphosphate receptors
  8. Role of thiols in the structure and function of inositol trisphosphate receptors
  9. Role of inositol trisphosphate receptors in autophagy in DT40 cells
  10. Linking structure to function: Recent lessons from inositol 1,4,5-trisphosphate receptor mutagenesis
  11. Surface accessibility and conformational changes in the N-terminal domain of type I inositol trisphosphate receptors: Studies using cysteine substitution mutagenesis
  12. Regulation of single inositol 1,4,5-trisphosphate receptor channel activity by protein kinase A phosphorylation
  13. Molecular characterization of the inositol 1,4,5-trisphosphate receptor pore-forming segment
  14. Role of inositol 1,4,5-trisphosphate receptors in apoptosis in DT40 lymphocytes
  15. IP3 receptors in cell survival and apoptosis: Ca2+ release and beyond
  16. The role of the S4-S5 linker and C-terminal tail in inositol 1,4,5-trisphosphate receptor function
  17. Mechanism of proteasomal degradation of inositol trisphosphate receptors in CHO-K1 cells
  18. Akt kinase phosphorylation of inositol 1,4,5-trisphosphate receptors
  19. Reactivity of free thiol groups in type-I inositol trisphosphate receptors
  20. Hypoxia inducible factor 1α regulates T cell receptor signal transduction