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Prasad R Konkalmatt
 

Prasad R Konkalmatt Ph.D.

Academic Title: Assistant Professor
Primary Appointment: Medicine
pkonkalmatt@medicine.umaryland.edu
Location: HSFII, S003
Phone: (410) 706-6020
Fax: (410) 706-6034

Personal History:

Hypertension is the most prevalent treatable cardiovascular disease that affects roughly one in four adults globally. Although it has long been recognized as an insidious adult-onset disorder, recent epidemiologic studies indicate that early predictors of hypertension are already found in the young. Hypertension results from genetically determined dysfunctions that are influenced by environmental factors (such as salt) and the individual’s lifestyle. A dysfunction of natriuretic systems (i.e., the elimination of excess body salt), such as the renal dopaminergic system, is implicated in the development of hypertension.

Previously, our lab showed that single nucleotide polymorphisms (SNPs) in G-protein coupled receptor kinase 4 (GRK4) gene cause impaired dopamine receptor function which results in defective sodium handling, and eventually to increased blood pressure. Dopamine-dependent activation of membrane receptors in the nephron plays a key role in maintaining water and salt homeostasis. Stimulation of the dopamine receptor leads to a cascade of well-characterized events that involve G protein uncoupling, receptor internalization, sorting and transport through the endosomal network, and either degradation or recycling.

The focus of my research interest is to study the molecular mechanisms by which GRK4 SNPs and dopamine receptors modulate hypertension and renal function. We will develop novel Adeno-associated virus (AAV) vectors for cell type-specific expression of genes of interest within the kidney, and employ these vectors in gene rescue experiments in their respective knock-out mice. We incorporate kidney-specific promoters in the AAV vector constructs in order to restrict the expression of the transgene to the desired cell type within the kidney. Thus, the physiological parameters measured will represent the function of the transgene expressed in specific cell types within kidney.

I have extensive experience in AAV biology and vector design for in vivo gene delivery in murine models.  In my graduate research at the Medical College of Ohio, I showed that the AAV Rep protein is covalently linked to the 5’ end of viral genomic DNA in the mature virion. During my post-doctoral training at the City of Hope National Medical Center, I acquired expertise on using AAV vector system for in vivo gene transfer. In my first faculty appointment at the University of Virginia, I established AAV vector system for cardiomyocyte-specific gene expression in a mouse model. Using this approach, we successfully demonstrated that cardiomyocyte-specific expression of EcSOD or iNOS protects the intact mammalian heart against myocardial infarction and heart failure.

Education and Training:

  • 1985-1988: University of Agricultural Sciences, Bangalore, India - M.S. in Biochemistry
  • 1989-1996: Medical College of Ohio, Toledo, OH - PhD in Biochemistry and Molecular Biology
  • 1996-1998: City of Hope National Medical Center, Duarte, CA - Post-doctoral training in Gene Therapy

Publications:

Prasad K.M.R., Yang Z.D., Bleich, D.M., Nadler, J. L., Adeno-associated virus vector mediated gene transfer to pancreatic Beta cells. Gene Therapy, 2000, 7, 1553-1561. PMID: 11021593.

Prasad KMR, Thimmalapura PRR, Woode EAA, Nadler J.L., Evidence that increased 12-lipoxygenase expression impairs pancreatic beta cell function and viability. BBRC. 2003, 308:427-432. PMID: 12914766.

Toufektsian MC, Yang ZQ, Prasad KMR, Overbergh L, Ramos SI, Mathieu C, Linden J and French BA. Stimulation of A2A-Adenosine receptors after myocardial infarction inhibits iNOS induction and attenuates contractile dysfunction in the remote left ventricle. Am J Physiol Heart Circ Physiol. 2006, 290:1410-18. PMID: 16284233.

Prasad KMR, Xu Y, Yang ZQ, Toufektsian MC, Berr SS, French BA. Topoisomerase Inhibition Accelerates the Onset of Gene Expression after Adeno-Associated Virus-Mediated Direct Gene Transfer to the Mammalian Heart. Mol. Therapy. 2007, 15:764-771. PMID: 17299410.

Gilson WD, Epstein FH, Yang Z, Xu Y, Prasad KMR, Toufektsian M.C., Laubach VE, French BA. Borderzone Contractile Dysfunction is Transiently Attenuated and Left Ventricular Structural Remodeling is Markedly Reduced Following Reperfused Myocardial Infarction in Inducible Nitric Oxide Synthase Knockout Mice. JACC. 2007, 50:1799-1807. PMID: 17964046.

Smith E, Prasad KMR, Butcher M, Kolls JK, Ley K, Galkina E. Blockade of IL-17A results in reduced atherosclerosis in Apoe-deficient mice. Circulation, 2010; 121:1746-1755. PMID: 20368519.

Saqib A, Prasad KMR, Katwal AB, Sanders JM, Lye RJ, French BA, Annex BH. AAV9-Mediated Overexpression of Extracellular Superoxide Dismutase Improves Recovery from Hind-limb Ischemia in BALB/c Mice. J. Vasc Surg. 2011; 54:810-8. 21723687.

Prasad KMR, Xu Y, Yang ZQ, Acton ST, Berr SS, French BA. Robust, Cardiac-Specific Gene Expression from a Single Systemic Injection of AAV: In Vivo Gene Transfer Follows a Poisson Distribution. Gene Therapy, 2011, 18:43-52. PMID: 20703310.

Prasad KMR, Robert SS, Xu Y, French BA. A Single Direct Injection into the Left Ventricular Wall of an AAV9 Vector Expressing EcSOD from the Cardiac Troponin-T Promoter Protects Mice Against Myocardial Infarction. J. Gene Med. 2011, 13:333-4. PMID: 21674736.

Konkalmatt PR*, Wang F, Xu Y, Piras BA, Beyers RJ, O’Conner DM, Annex BH, Hossack JA, French BA. Adeno-associated virus serotype 9 administered systemically after reperfusion preferentially targets cardiomyocytes in the infarct border zone with pharmacodynamics suitable for the attenuation of left ventricular remodeling. J Gene Med. 2012, 14:609-20. PMID: 23065925.

Konkalmatt PR*, Beyers RJ, Xu Y, O’Conner DM, French BA. Cardiac-Selective Overexpression of EcSOD Following a Single Intravenous Injection of AAV9 Protects the Heart Against both Myocardial Infarction and Subsequent LV Remodeling (Circulation: Cardiovascular Imaging; Manuscript under review).

Katwal AB, Konkalmatt PR*, Sanders JM, Sean SL, Lye RJ, Annex BH, French BA. Adeno-associated virus serotype 9 efficiently targets ischemic skeletal muscle following systemic delivery (Gene Therapy; Manuscript under review).

*Konkalmatt PR formerly Prasad KMR