Brent A. French Brent A. French

Professor of Biomedical Engineering


Ph.D., Biochemistry, Louisiana State University, 1987

UVA Health System
Box 800759
Charlottesville, VA 22908

Office: Room 1121 Phone: 434-924-5728
Lab: Room 1219 Phone: 434-243-9343

bf4g@virginia.edu

   

Research Interests

Interplay of Nitric Oxide with Superoxide in Health and Disease

The basic research focus of our laboratory is to determine the physiological significance of the balance that exists between nitric oxide and superoxide in the cardiovascular systems of higher mammals. Recent investigations indicate that this balance becomes critical in the setting of heart attack. Nitric oxide and superoxide are free radicals that react spontaneously to form peroxynitrite, a very destructive reactive oxygen species. Basic research efforts in the laboratory are focused on determining the roles played by nitric oxide, superoxide and peroxynitrite in both the acute and chronic settings of myocardial infarction.

Novel Therapies for Cardioprotection and Cardiopreservation

The applied research focus of the laboratory is to develop novel therapies to protect the intact mammalian heart against myocardial infarction and heart failure. An interdisciplinary approach is used to integrate recent advances in molecular biology with cutting-edge imaging techniques such as MRI and echocardiography to expedite research by accurately measuring the effect of novel therapies on cardiovascular disease. Accurate animal models of myocardial stunning, infarction and left ventricular remodeling after myocardial infarction have been implemented in rabbits, rats and mice. Using direct gene transfer techniques in these models, we have previously shown that either superoxide dismutase or nitric oxide synthase can provide the heart with substantial protection against myocardial infarction (i.e., reduce the extent of myocardial infarction by > 50%). Recently, the excess production of superoxide and nitric oxide have also been implicated in the progressive loss of cardiac function that characterizes heart failure after myocardial infarction. Thus we anticipate that gene therapy with superoxide dismutase may also prove beneficial in the setting of left ventricular remodeling after myocardial infarction by reducing the formation of peroxynitrite and thereby controlling oxidative damage in the heart and vasculature.

Selected Publications

Dasa SS, Suzuki R, Gutknecht M, Brinton LT, Tian Y, Michaelsson E, Lindfors L, Klibanov AL, French BA, Kelly KA. Development of target-specific liposomes for delivering small molecule drugs after reperfused myocardial infarction. J Control Release. 28(220 Pt A):556-67, 2015.

Tian Y, French BA, Kron IL, Yang Z. Splenic leukocytes mediate the hyperglycemic exacerbation of myocardial infarct size in mice. Basic Res Cardiol. 110(4):39-54, 2015.

Konkalmatt PR, Beyers RJ, O'Connor DM, Xu Y, Seaman ME, French BA. Cardiac-selective expression of extracellular superoxide dismutase after systemic injection of adeno-associated virus 9 protects the heart against post-myocardial infarction left ventricular remodeling. Circulation: Cardiovascular Imaging. 6(3):478-86, 2013.

Katwal AB, Konkalmatt PR, Piras BA, Hazarika S, Li SS, Lye RJ, Sanders JM, Ferrante EA, Yan Z, Annex BH and French BA. Adeno-associated virus serotype 9 efficiently targets ischemic skeletal muscle following systemic delivery. Gene Therapy 20(9):930-938, 2013.

Prasad K.M.R., Xu Y., Yang Z., Acton S.T., French B.A. Robust cardiomyocyte-specific gene expression following systemic injection of AAV: In vivo gene delivery follows a Poisson distribution. Gene Therapy 18(1):43-52, 2011.

Click here for complete list of publications in PubMed