Our laboratory has a highly focused program to investigate the basic and applied functions of the hormone somatostatin.
Somatostatin is widely distributed in different brain regions and involved in locomotor and cognitive function. Our first project concerns understanding the role of somatostatin in neurodegenerative diseases such as Alzheimer's and Huntington's disease. Somatostatin's biological effect is mediated by five different receptor subtypes, namely somatostatin receptors 1-5 (SSTR1-5). These receptors are members of G-protein-coupled receptor family (GPCR). G-protein-coupled receptors constitute the largest number of cell surface proteins in the human genome and are targets for the development of new therapeutic drugs. Homo- and hetero-oligomerization of GPCRs suggest a functional interaction with enhanced pharmacological and signalling properties.
Accordingly, our second project concentrates on the molecular pharmacology and biology of somatostatin receptors and other GPCRs such as dopamine and opioid receptors, using pbFRET analysis to determine receptor dimerization and agonist-dependent desensitization and upregulation.
Our third project investigates the antiproliferative activity of somatostatin. Our studies focus on the roles of somatostatin receptor subtypes and the signaling pathways through which somatostatin receptors are involved in breast cancer and may exert an antiproliferative effect on tumor growth.
Kumar, U., Grigorakis, S.I., Watt, H.L., Watson, P., and Chaudhari, S."Immunohistochemical and mRNA expression of SSTR types 1-5 in primary human breast cancer: Correlation with tumor pathology, estrogen, and progesterone receptor status", Breast Cancer Research and Treatment 92 (2): 175-186 (2005).
Kumar, U., Chen, J., Sapoznikhov, V., Canteros, G., White, B.H. and Sidhu, A."Overexpression of inducible nitric oxide synthase in the kidney of the spontaneously hypertensive rat", Experimental Clinical Hypertension 1: 17-31 (2005).
Kumar, U. "Expression of somatostatin receptor subtypes (SSTR1-5) in Alzheimer's Disease (AD) brain: An immunohistochemical analysis", Neuroscience 134, 525-538 (2005).
Ramirez, J-L, Watt, H.L., Rocheville, M., and Kumar, U. "Agonist-induced upregulation of human somatostatin receptor type 1 is regulated by b-arrestin-1 and requires an essential serine residue in the receptor C-tail", Biochim Biophys Acta (Biomembranes) 1669 (2): 182-192 (2005).
Goodyer, C.G., Grigorakis, S.I., Patel, Y.C. and Kumar, U. "Developmental changes in the expression of somatostatin receptors (1-5) in the brain, hypothalamus, pituitary and spinal cord of the human fetus", Neuroscience 125:441-448 (2004).
Grant, M., Patel, R.C. and Kumar, U. "The role of subtype-specific ligand binding and the C-tail domain in dimer formation of human somatostatin receptor", Journal of Biological Chemistry 279 (37): 38636-38643 (2004).
Grant, M., Collier, B. and Kumar, U. "Agonist-dependent dissociation of human somatostatin receptor 2 dimers: A role of receptor trafficking", Journal of Biological Chemistry 279 (35): 36179-36183 (2004).
Kumar, U. "Characterization of striatal cultured neurons in QUIN and NMDA induced toxicity", Neuroscience Research 49:29-38 (2004).
Kumar, U. "Differential expression of Huntington's gene (IT15) mRNA in developing rat brain", Molecular Brain Research 128:39-47 (2004).
Mouchantaf, R., Traian, S., Seidah, N.G., and Kumar, U. "Prosomatostatin is proteolytically processed at the amino terminal segment by the subtilase SKI-1", Regulatory Peptides 120 (1-3):133-140 (2004).
Ramirez, J-L, Grant, M., Norman, M., Moldovan, S., de Mayo, F.J., Brunicardi, C., and Kumar, U. "Deficiency of somatostatin (SST) receptor subtype 5 (SSTR5) is associated with sexually dimorphic changes in the expression of SST and SST receptors in brain and pancreas", Molecular and Cellular Endocrinology 221 (1-2):105-119 (2004).
Kumar, U., Wersinger, C., Patel, Y.C. and Sidhu, A. "Diminished expression of constitutive nitric oxide synthases in the kidney of spontaneously hypertensive rat", Clinical and Experimental Hypertension 25(4):271-282 (2003).
Patel R.C., Kumar, U., Lamb, D.C., Eid, J.S., Rocheville, M., Grant, M., Rani, A., Hazlett,T., Patel, S.C., Gratton, E., and Patel, Y.C. "Ligand binding to somatostatin receptors induces receptor specific oligomer formation in live cells", PNAS (USA) 99(5):3294-3299 (2002).
Rocheville, M., Lange, D., Kumar, U., Sasi, R., Patel, R.C., and Patel, Y.C. "Subtypes of the somatostatin receptor assemble as functional homo- and heterodimers", Journal of Biological Chemistry 275:7862-7869 (2000).
Rocheville, M., Lange, D., Kumar, U., Patel, S.C., Patel, R.C., and Patel, Y.C."Receptors for dopamine and somatostatin form heterodimers with enhanced functional activity", Science 288:154-157 (2000).