Indu Ambudkar, Ph.D., M.Sc.
Secretory Physiology Section
Acting Scientific Director
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.
Dr. Indu Ambudkar received her M.Sc. degree from Lucknow University and her Ph.D. from Madurai Kamaraj University in India. She joined the University of Maryland, School of Medicine, as a post-doctoral researcher in 1980 and continued as a Research Assistant Professor from 1983 to 1985.
Dr. Ambudkar moved to the National Institute of Dental and Craniofacial Research in 1985 as a Tenure Track Research Fellow and is currently Chief of the Secretory Physiology Section. Research in her laboratory is focused on the molecular mechanisms mediating and regulating Ca2+ entry in salivary gland cells, with special focus on TRP and Orai channels and the ER-proteins STIM1 and STIM2 which play key roles in regulation of Ca2+ entry and Ca2+ signaling.
Dr. Ambudkar's studies have identified critical Ca2+ signaling defects that underlie loss of salivary gland fluid secretion caused by radiation treatment and the autoimmune disease Sjogren’s Syndrome. Her research also seeks to identify Ca2+ signaling mechanisms and components that contribute to disease and dysfunction. She is internationally recognized for her contributions in this area and has chaired several major conferences.
Dr. Ambudkar is a Steering Committee Member of the NIH-FAN group and has served on the NIH-Diversity and Equity Committee as well as the NIH-women Scientific Advisory Committee. She is a recipient of the Distinguished Researcher Award from the International Association of Dental Research, the NIH Director’s Award of Excellence, and the NIDCR Honor Award for Mentoring.
- 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.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on Tuesday, November 14, 2023