PHA/AHA Post Doctoral Fellowship Award Winner 2010
Swapnil Sonkusare, PhD
University of Vermont, Burlington
“TRPV4 and pressure modulation of calcium signaling in vascular endothelium”
Term: July 1, 2010 – June 30, 2012
Summary of Research Project:
1. What is the major problem being addressed by this study?
Small arteries in the body constrict when the pressure inside them increases, in order to control the blood flow to target organs. However, excessive constriction of the small arteries can increase the blood pressure and reduce blood flow to target organs. We propose a novel pathway that regulates the constriction of small arteries to an increase in pressure. This pathway, when activated, dilates the arteries. This mechanism can be used to treat high blood pressure and disorders that are characterized by reduced blood flow to target organs.
2. What specific questions are you asking and how will you attempt to answer them?
Using arteries from mice, we have discovered that when this regulatory pathway is activated using a drug it results in dilation of the small arteries. We propose that increase in pressure inside the arteries activates a protein on the inner wall of the artery, which then activates other components of the pathway to produce dilation of artery. We propose to study the mechanism that activates this protein, and also the pathway that produces dilation of the arteries following activation of this protein.
3. What is the long-term biomedical significance of your work, particularly as it pertains to the cardiovascular area? What major therapeutic advance(s) do you anticipate that it will lead to? For instance, new drug(s), a surgical technique/procedure, a diagnostic tool/test, a previously undetected risk factor, etc.
This study will help us understand a phenomena that helps us regulate the blood pressure and also the blood flow to target organs. The understanding of this regulatory pathway will result in several targets that can be activated to either lower the blood
pressure in hypertensive patients and to increase the blood flow to target organs in disorders such as stroke or diabetes.
NAME: Swapnil Sonkusare, Ph.D.
POSITION TITLE: Postdoctoral Associate
|INSTITUTION AND LOCATION
||FIELD OF STUDY
|Nagpur University, India
|National Institute of Pharmaceutical Education and
Research (NIPER), Mohali, India
|University of Arkansas for Medical Sciences (UAMS),
|University of Vermont (postdoc), USA
Academic and Professional Honors
- National Scholarship for Master’s in Pharmacology, India, 2002-2003
- Graduate School Travel Award for Experimental Biology, 2006-2008
- Graduate student Best Paper award; third position, Cardiovascular Division of ASPET,
- Experimental Biology Meeting, San Francisco, 2006
- American Heart Association Travel Award for 6 th Hypertension Summer School at Fort Collins, Colorado, 2007
- Winner of Seager-Braswell Student Symposium, Junior Division, Department of Pharmacology and Toxicology, UAMS, 2008
- Graduate Student Best Abstract Award, Runner-up, Cardiovascular Division of ASPET, Experimental Biology, San Diego, 2008
- Chaired the symposium titled ‘Regulation of ion channels in cardiovascular diseases’, Experimental Biology, San Diego, 2008
- Runner-Up, Seager-Braswell Student Symposium, Senior Division, Department of Pharmacology and Toxicology, UAMS, 2009
- Representing ASPET Cardiovascular Division as Postdoctoral Scientist during All division mixer at Experimental Biology, Anaheim, 2010
- American Society of Pharmacology and Experimental Therapeutics (ASPET), Served on the Program Committee and the Competition Committee of cardiovascular pharmacology Division
- American Physiological Society (APS)
- American Heart Association (AHA)
Research papers and Reviews
1. Sonkusare SK, Kaul CL, Ramarao P. Dementia of Alzheimer’s disease and other neurodegenerative disorders- memantine, a new hope, Pharmacological Research 51: 1-17, 2005.
2. Sonkusare S, Srinivasan K, Kaul C, Ramarao P. Effect of donepezil and lercanidipine on intracerebroventricular streptozotocin induced memory impairment in rats, Life Sciences 77: 1-14, 2005.
3. Pathan AR, Viswanad B, Sonkusare SK, Ramarao P. Chronic administration of pioglitazone attenuates intracerebroventricular streptozotocin induced-memory impairment in rats. Life Sciences, 79: 2209-16, 2006.
4. Sonkusare S, Palade PT, Marsh JD, Telemaque S, Pesic A, Rusch NJ. Vascular calcium channels and high blood pressure: Pathophysiology and therapeutic implications, Vascular Pharmacology 44: 131-142, 2006.
5. Telemaque S, Sonkusare S*, Grain T, Stimers JR, Rhee SW, Rusch NJ, Marsh JD. Design of Mutant β2 Subunits as Decoy Molecules to Reduce the Expression of Functional Ca2+ Channels in Cardiac Cells. Journal of Pharmacology and Experimental Therapeutics, 325 :37-46, 2008 .
6. Sonkusare S, Fraer M, Marsh JD, Rusch NJ. Disrupting calcium channel expression to lower blood pressure: new targeting of a well-known channel. Molecular Interventions, 6: 304-310, 2006.
7. Thakali KM, Kharade SV, Sonkusare SK, Rhee SW, Stimers JR, Rusch NJ. Intracellular Calcium Silences L-Type Ca2+ Channels: Mechanism of Venous Smooth Muscle Insensitivity to Calcium Channel Blockers. Circulation Research, 2009, [Epub ahead of print].
*: Co-first author.
1. Swapnil K. Sonkusare, Thomas J. Heppner, Adrian D. Bonev, Rachael M. Hannah, Yvonne Talline, Michael I. Kotlikoff, Mark T. Nelson. High intravascular pressure decreases endothelial Ca2+ pulsars and impairs endothelium-dependent vasodilation in mouse mesenteric arteries, Experimental Biology 2010, Anaheim, CA.
2. Sujay V. Kharade, Swapnil Sonkusare, Sung W. Rhee, Nancy J. Rusch. Vascular α1C and β3 subunits of L-type calcium channels are coordinately upregulated in the mesenteric arteries of hypertensive C57BL6 mice, FASEB J, Apr 2009; 23: 579.11.
3. Li Pang, Swapnil Sonkusare, Keshari Thakali, Russell Melchert, Kerrey Roberto, and Philip Palade. AAV-mediated vascular smooth muscle-specific knockdown of Cav1.2 as a long-term anti-hypertensive therapy, FASEB J, Apr 2009; 23: 932.4.
4. Swapnil Sonkusare, Sung W. Rhee, Keshari Thakali, Terry W. Fletcher, Joseph R. Stimers, Sabine Telemaque, Nancy J. Rusch. Accessory β3 subunits promote the functional expression of voltage-gated calcium channels in vascular smooth muscle cells, FASEB J, Mar 2008; 22:912.35.
5. Sujay Kharade, Swapnil Sonkusare, Terry W. Fletcher, Lee Ann Macmillan-Crow, Nancy J. Rusch. Exposure to H2O2 rapidly down-regulates L-type calcium channels in A7r5 cells, FASEB J, Mar 2008; 22: 912.36.
6. Keshari Thakali, Swapnil Sonkusare, Joseph R. Stimers, Nancy J. Rusch, L-type Ca2+ channels are expressed but not activated by KCl in rat small mesenteric veins, FASEB J, Mar 2008; 22: 912.31.
7. Swapnil Sonkusare, Joseph R. Stimers, Terrie Grain, James D. Marsh, Sabine Telemaque, Expression of a β2 subunit mutant alters calcium Ca2+ currents in HL-1 cells, FASEB J, Mar 2006; 20: A1114 - A1115.