Sonkusare Lab

Robert M. Berne Cardiovascular Research Center

Department of Molecular Physiology and Biological Physics

University of Virginia School of Medicine

Mission Statement

Identify the calcium signaling abnormalities that lead to vascular dysfunction and blood pressure elevation in cardiovascular disorders

The Sonkusare laboratory studies the role of ion channels and calcium signaling mechanisms in regulating vascular function and blood pressure. Constriction of small arteries is a crucial determinant of blood pressure. Smooth muscle cells are the contractile cells in the arterial wall, whereas endothelial cells regulate smooth muscle contraction. Calcium signaling mechanisms in endothelial and smooth muscle cells are critical controllers of arterial constriction. Moreover, abnormal calcium handling in endothelial and smooth muscle cells has been implicated in blood pressure elevation in hypertension. Thus, strategies targeting arterial calcium signaling abnormalities may have therapeutic benefit in hypertension.

We use numerous transgenic knockout mouse models and a combination of state-of-the-art techniques, including high-speed confocal imaging of individual calcium signals, patch clamp electrophysiology to assess the activity of calcium channels (proteins that allow calcium flux), dSTORM super-resolution imaging to visualize calcium channel proteins, and measurements of arterial diameter and blood pressure. Please take a look at the Images acquired using different technologies available in the Sonkusare laboratory. For our most current list of publications, please click here (https://pubmed.ncbi.nlm.nih.gov/?term=Sonkusare+Swapnil%5BAuthor%5D&sort=date).

Lab twitter: @sonkusarelab

A major focus of current studies is the role of TRP ion channels in blood pressure regulation. TRP channels are a major calcium entry pathway in endothelial and smooth muscle cells. TRP channels have signaling linkages with other calcium channels, potassium channels, and nitric oxide synthases. Multiple physiological stimuli in endothelial and smooth muscle cells can activate TRP channels in arterial walls, including flow/shear stress, G-protein coupled receptor signaling, and intraluminal pressure. The ultimate goal is to discover specific abnormalities in calcium signaling mechanisms that can be targeted for therapeutic benefit in the following disease conditions:

  1. Obesity-induced hypertension. Obesity has become a life-threatening health concern and a major risk factor for cardiovascular disease, including hypertension and stroke. Endothelial cell dysfunction is a hallmark of obesity. We investigate the mechanisms underlying impaired endothelial calcium signaling and potential ways to target this abnormality. Our ongoing studies suggest an essential role for vascular inflammation and resultant oxidative stress in impairing endothelial and smooth muscle calcium signaling in obesity.
  2. Pulmonary hypertension. Pulmonary hypertension (PH) is a serious disorder characterized by elevated pulmonary arterial pressure (PAP). The contractile state of small pulmonary arteries determines PAP. Our previous studies showed a key role for Pannexin 1 (ATP efflux pathway), purinergic signaling, and TRP channels in controlling pulmonary artery diameter and PAP. Current studies determine whether impaired activity of these proteins contributes to pulmonary artery constriction and remodeling in pulmonary hypertension.
  3. Hypertension. Nearly one out of two adults has hypertension in the US. Abnormal calcium handling in arterial smooth muscle cells has been implicated in hypertension. We study calcium signaling mechanisms in smooth muscle cells that regulate blood pressure under normal conditions and are impaired in hypertension. We use mouse models of hypertension and tissue from hypertensive patients to delineate cellular mechanisms underlying arterial dysfunction.
  4. Atherosclerosis. Atherosclerosis is a chronic inflammatory disease of the arteries and is the underlying cause of about 50% of all deaths in western society. Our studies delineate vascular calcium signaling abnormalities that contribute to the pathogenesis of atherosclerosis.
  5. Lung ischemia-reperfusion injury. Outcomes of lung transplantation are poor, with nearly half of the patients die within 6-7 years post-transplant. Lung ischemia-reperfusion injury (IRI) is a significant cause of death post-transplant. Our studies show an essential role for capillary endothelial TRP channels in lung IRI, and demonstrate beneficial effects of TRP channel inhibitors in preventing lung IRI.

Selected Publications

  1. Chen YL, Daneva Z, Kuppusamy M, Ottolini M, Baker TM, Klimentova E, Shah SA, Sokolowski JD, Park MS, Sonkusare SK. Novel Smooth Muscle Calcium Signaling Nanodomains in Blood Pressure Regulation. Circulation, 2022 (in press). PMID: 35758040.

  2. Daneva Z, Ottolini M, Chen YL, Kuppusamy M, Klimentova E, Shah S, Seye C, Minshall RD, Laubach VE, Sonkusare SK. Endothelial Pannexin 1-purinergic signaling lowers pulmonary arterial pressure. eLife. 10:e67777, 2021. PMCID: PMC8448527.

  3. Daneva Z, Marziano C, Ottolini M, Chen YL, Baker TM, Kuppusamy M, Zhang A, Ta HQ, Reagan CE, Mihalek AD, Kasetti RB, Shen Y, Isakson BE, Minshall RD, Zode GS, Goncharova EA, Laubach VE, Sonkusare SK. Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension. Proceedings of The National Academy of Sciences of The United States of America. 118(17):e2023130118, 2021. PMCID: PMC8092599.

  4. Patel PD, Chen YL, Kasetti R, Maddineni P, Mayhew W, Millar JC, Ellis DZ, Sonkusare SK (co-corresponding), Zode GS (co-corresponding), Impaired TRPV4-eNOS signaling in trabecular meshwork elevates intraocular pressure in glaucoma. Proceedings of The National Academy of Sciences of The United States of America. 118(16):e2022461118, 2021. PMCID: PMC8072326.

  5. Ottolini M, Hong K, Cope EL, Daneva Z, DeLalio LJ, Sokolowski JD, Marziano C, Nguyen NY, Altschmied J, Haendeler J, Johnstone SR, Kalani MY, Park MS, Patel RP, Liedtke W, Isakson BE, Sonkusare SK. Local peroxynitrite impairs endothelial TRPV4 channel activity and elevates blood pressure in obesity. Circulation, 141(16):1318-1333, 2020. PMCID: PMC7195859.


Currently Hiring

Accepting applications for postdoctoral positions. Please email Dr. Sonkusare at sks2n@virginia.edu.


Sponsored Projects

  1. R01 HL142808; AKAP150-TRPV4 REGULATION OF ENDOTHELIAL FUNCTION IN OBESITY. Principal Investigator: Dr. Swapnil Sonkusare.
  2. R01 HL146914; CAV-1.TRPV4 REGULATION OF ENDOTHELIAL FUNCTION IN SMALL PULMONARY ARTERIES. Principal Investigator: Dr. Swapnil Sonkusare.
  3. R01 HL157407; Role of TRPV4 channel signaling in lung ischemia-reperfusion injury. Principal Investigators: Drs. Laubach and Sonkusare.
  4. R01 HL147555; NEW SIGNALING NETWORKS IN VASCULAR SMOOTH MUSCLE. Principal Investigators: Drs. Somlyo, Sonkusare, and Derewenda.
  5. R21 NS118647; RHOA SIGNALING AND STROKE. Principal Investigators: Drs. Derewenda, Somlyo, and Sonkusare.

Associated Sites at UVa

Robert M. Berne Cardiovascular Research Center (aka CVRC)
Department of Molecular Physiology and Biological Physics
Cardiovascular Training Grant (CVTG and Facebook)