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Indu S. Ambudkar, Ph.D., M.Sc.

Indu S. Ambudkar, Ph.D., M.Sc.Chief, Secretory Physiology Section
Chief, Molecular Physiology and Therapeutics Branch

NATIONAL INSTITUTES OF HEALTH/NIDCR
BUILDING 10 ROOM 1N113
10 CENTER DR MSC 1190
BETHESDA MD 20892-1190

Phone: (301) 496-5298
Fax: (301) 402-1228
E-mail: Indu.Ambudkar@nih.gov

Biographical Sketch

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.

PROFESSIONAL – Work Experience

2007 Chief, GTTB, NIDCR, NIH
2006–2007 Acting Chief, MPTB, NIDCR, NIH
1993–present Chief, Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, NIDCR, NIH
1988–1993 Senior Staff Fellow (Tenure-track), Clinical Investigations and Patient Care Branch, NIDR, NIH
1991–1996 Adjunct Assistant Professor, Department of Pathology, University of Maryland, School of Medicine, Baltimore, MD
1985–1988 Visiting Associate, Clinical Investigations and Patient Care Branch, NIDR, NIH, Bethesda, MD
1984–1985 Research Assistant Professor, Department of Pathology, School of Medicine, Baltimore, MD
1980–1983 Research Associate, Department of Biological Chemistry, University of Maryland, School of Medicine, Baltimore, MD

RECENT HONORS, AWARDS, & ACTIVITIES

  • NIH Merit Award, 2000.
  • Member, Oral Biology and Medicine, Study Section, 1997-2000
  • Administrative Chair WSA Committee, NIH (2005-2008)
  • Woman Scientists’ Advisor to the Scientific Director, NIDR, 1993-1998, 2002-present
  • Member of the NIH Women’s Advisory group
  • Co-Chair, NIH-Calcium Interest Group, 1997-present

Meetings/Conferences

  • Chair, Gordon Conference on Calcium Signaling, 2007
  • Co-Chair; Gordon Conference on Calcium Signaling, 2005
  • Vice-Chair Elect; Salivary gland and excocrine secretion GRC, 2011
  • Chair Elect; Salivary gland and excocrine secretion GRC, 2013

Editorial

  • Faculty Member, Faculty of 1000 Biology
  • Review Editorial Board of Frontiers in Pharmacology of Ion Channel and Channelopathies
  • Editorial Board Member: Cell Calcium
  • Editorial Board member: Journal of Biological Chemistry
  • Member Editorial Board, Journal of Dental Research. 1996-1999
  • Member Editorial Board, Membrane Biochemistry. 1991-1996

Research Interests/Scientific Focus

Ca2+ signaling mechanisms and cell functionNeurotransmitter regulation of salivary secretion is mediated by a sustained increase in intracellular [Ca2+] ([Ca2+]i) which is due to store-operated Ca2+ entry (SOCE), activated in response to IP3-depletion of ER calcium stores. This sustained elevation in [Ca2+]i regulates a number of key ion flux systems which concertedly drive salivary gland (SG) fluid secretion. Emerging studies reveal that cellular Ca2+, and more specifically Ca2+ entry, also regulates key mechanisms associated with gene expression, cell growth, differentiation, inflammation, and cell death. Our long term goal is to define the components that mediate and regulate Ca2+ entry into salivary gland cells and characterize the role of these in normal physiology as well as dysfunction/disease of salivary glands.

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.

We are also utilizing proteomic techniques to elucidate possible protein-protein interactions involving TRPC1, Orai1, and STIM1. By using the SILAC method and a shot-gun approach, we get a global read-out of the proteome associated with the channels in resting and stimulated conditions. Several interesting candidates have been identified and are currently being validated. Another approach to examine downstream effectors of Ca2+ signaling is by cDNA array analysis. We aim to identify key cell signaling networks that are regulated by Ca2+ that participate in salivary gland physiology or pathophysiology.

Another major area of focus is salivary gland damage associated with radiation treatment as well as Sjögren's syndrome. Major efforts are directed to understanding the role of the ROS-sensitive cation channel TRPM2 in salivary gland damage induced by irradiation and inflammation. Functional studies are being carried out to demonstrate the role of this channel in these processes. We propose that TRPM2 is a potentially useful target in strategies of protection of salivary gland function. Studies are also ongoing to look at the status of STIM1, Orai1, and TRPC channel proteins in pSS salivary glands and lymphocytes. The strategy is to modify locally within the salivary gland, by delivery of viral vectors, the expression of specific proteins (knock down or overexpression) and then assess the effects in normal secretion and in salivary dysfunction.

Selected Publications

  1. Ma X, Cheng KT, Wong CO, O'Neil RG, Birnbaumer L, Ambudkar IS, Yao X. Heteromeric TRPV4-C1 channels contribute to store-operated Ca(2+) entry in vascular endothelial cells. Cell Calcium. 2011 Sep 17. [Epub ahead of print]
  2. Pla AF, Avanzato D, Munaron L, Ambudkar IS. VASCULARIZING THE TUMOR: TRP CHANNELS AS MOLECULAR TARGETS. Am J Physiol Cell Physiol. 2011 Aug 10. [Epub ahead of print]
  3. Ong HL, Ambudkar IS. The dynamic complexity of the TRPC1 channelosome. Channels (Austin). 2011 Sep 1;5(5):424-31. Epub 2011 Sep 1.
  4. Fiorio Pla A, Ong HL, Cheng KT, Brossa A, Bussolati B, Lockwich T, Paria B, Munaron L, Ambudkar IS. TRPV4 mediates tumor-derived endothelial cell migration via arachidonic acid-activated actin remodeling. Oncogene. 2011 Jun 20. doi: 10.1038/onc.2011.231. [Epub ahead of print]
  5. Ambudkar IS. Dissection of calcium signaling events in exocrine secretion. Neurochem Res. 2011 Jul;36(7):1212-21. Epub 2011 May 2. Review.
  6. Cheng KT, Liu X, Ong HL, Swaim W, Ambudkar IS. Local Ca²+ entry via Orai1 regulates plasma membrane recruitment of TRPC1 and controls cytosolic Ca²+ signals required for specific cell functions. PLoS Biol. 2011 Mar;9(3):e1001025. Epub 2011 Mar 8.
  7. Cheng KT, Ong HL, Liu X, Ambudkar IS. Contribution of TRPC1 and Orai1 to Ca(2+) entry activated by store depletion. Adv Exp Med Biol. 2011;704:435-49. Review.
  8. Hong JH, Li Q, Kim MS, Shin DM, Feske S, Birnbaumer L, Cheng KT, Ambudkar IS, Muallem S. Polarized but differential localization and recruitment of STIM1, Orai1 and TRPC channels in secretory cells. Traffic. 2011 Feb;12(2):232-45. doi: 10.1111/j.1600-0854.2010.01138.x. Epub 2010 Nov 24.
  9. Liu X, Ong HL, Pani B, Johnson K, Swaim WB, Singh B, Ambudkar I. Effect of cell swelling on ER/PM junctional interactions and channel assembly involved in SOCE. Cell Calcium. 2010 Jun;47(6):491-9. Epub 2010 May 20.
  10. Pani B, Ong HL, Brazer SC, Liu X, Rauser K, Singh BB, Ambudkar IS. Activation of TRPC1 by STIM1 in ER-PM microdomains involves release of the channel from its scaffold caveolin-1. Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):20087-92. Epub 2009 Nov 6.
  11. Bandyopadhyay BC, Ong HL, Lockwich TP, Liu X, Paria BC, Singh BB, Ambudkar IS. TRPC3 controls agonist-stimulated intracellular Ca2+ release by mediating the interaction between inositol 1,4,5-trisphosphate receptor and RACK1. J Biol Chem. 2008 Nov 21;283(47):32821-30. Epub 2008 Aug 28.
  12. Pani B, Ong HL, Liu X, Rauser K, Ambudkar IS, Singh BB. Lipid rafts determine clustering of STIM1 in endoplasmic reticulum-plasma membrane junctions and regulation of store-operated Ca2+ entry (SOCE). J Biol Chem. 2008 Jun 20;283(25):17333-40. Epub 2008 Apr 22.
  13. Cheng KT, Liu X, Ong HL, Ambudkar IS. Functional requirement for Orai1 in store-operated TRPC1-STIM1 channels. J Biol Chem. 2008 May 9;283(19):12935-40. Epub 2008 Mar 7.
  14. Lockwich T, Pant J, Makusky A, Jankowska-Stephens E, Kowalak JA, Markey SP, Ambudkar IS. Analysis of TRPC3-interacting proteins by tandem mass spectrometry. J Proteome Res. 2008 Mar;7(3):979-89. Epub 2008 Jan 19.
  15. Liu X, Cheng KT, Bandyopadhyay BC, Pani B, Dietrich A, Paria BC, Swaim WD, Beech D, Yildrim E, Singh BB, Birnbaumer L, Ambudkar IS. Attenuation of store-operated Ca2+ current impairs salivary gland fluid secretion in TRPC1(-/-) mice. Proc Natl Acad Sci U S A. 2007 Oct 30;104(44):17542-7. Epub 2007 Oct 23





Complete CV and Publications (PDF File, 126KB)

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This page last updated: February 26, 2014