Our studies utilize a variety of approaches, including electrophysiology, cellular imaging, molecular biology, as well as biochemistry to determine the molecular basis of Ca2+ entry in salivary gland acini and the role of Ca2+ entry in fluid secretion. Our recent and ongoing studies are directed towards identifying the function, regulation, trafficking and assembly of the transient receptor potential channel, TRPC1. We have provided evidence that TRPC1 is an essential component of the agonist-stimulated Ca2+ influx mechanism that is required for sustained saliva secretion. We have identified two other important components of this mechanism, the calcium channel, Orai1, and the ER regulator of calcium channels, STIM1. Current studies are directed to understand and define the individual contributions of TRPC1 and Orai1 to salivary fluid secretion. We are also interested in identifying the regulation of the water channel, AQP5, during stimulation of the gland and secretion. Our work has led to the identification of TRPV4 as an essential TRP channel that is involved in cellular volume regulation. In addition, other TRPC channels, TRPC3 and TRPC6, could also have important role in regulating other aspects of salivary gland function. These studies are ongoing.
EDUCATION: 1973, B.Sc. (Biology), Isabella Thoburn College, Lucknow, India; 1975 M.Sc. (Biochemistry), Lucknow University, Lucknow, India. 1980 Ph.D. (Biochemistry), Madurai Kamaraj University Madurai, India.
- Son GY, Subedi KP, Ong HL, Noyer L, Saadi H, Zheng C, Bhardwaj R, Feske S, Ambudkar IS. STIM2 targets Orai1/STIM1 to the AKAP79 signaling complex and confers coupling of Ca2+ entry with NFAT1 activation. Proc Natl Acad Sci U S A. 2020;117(28):16638-16648.
- Subedi KP, Ong HL, Son GY, Liu X, Ambudkar IS. STIM2 Induces Activated Conformation of STIM1 to Control Orai1 Function in ER-PM Junctions. Cell Rep. 2018;23(2):522-534.
- Liu X, Gong B, de Souza LB, Ong HL, Subedi KP, Cheng KT, Swaim W, Zheng C, Mori Y, Ambudkar IS. Radiation inhibits salivary gland function by promoting STIM1 cleavage by caspase-3 and loss of SOCE through a TRPM2-dependent pathway. Sci Signal. 2017;10(482).
- Ahmad M, Ong HL, Saadi H, Son GY, Shokatian Z, Terry LE, Trebak M, Yule DI, Ambudkar I. Functional communication between IP3R and STIM2 at subthreshold stimuli is a critical checkpoint for initiation of SOCE. Proc Natl Acad Sci U S A. 2022;119(3).
- Ong HL, de Souza LB, Zheng C, Cheng KT, Liu X, Goldsmith CM, Feske S, Ambudkar IS. STIM2 enhances receptor-stimulated Ca²⁺ signaling by promoting recruitment of STIM1 to the endoplasmic reticulum-plasma membrane junctions. Sci Signal. 2015;8(359):ra3.
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Molecular Biology and Biochemistry
This page was last updated on Wednesday, August 10, 2022