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Van Anthony M. Villar

Van Anthony M. Villar M.D., Ph.D.

Academic Title: Assistant Professor
Primary Appointment: Medicine
Location: HSF-II, S003C
Phone: (410) 706-6014
Fax: (410) 706-6034

Personal History:

Dr. Villar received his MD degree from Our Lady of Fatima University in the Philippines in 1993 and his PhD in Molecular Biology and Biotechnology from the University of the Philippines (Diliman) in 2008. He was an Assistant Professor and a Senior Research Scientist at the Department of Biochemistry and Nutrition, College of Medicine, Our Lady of Fatima University. Upon completion of his PhD, he was granted a position as Research Faculty at Children’s National Medical Center with joint appointment as Assistant Professor of Pediatrics at the George Washington University School of Medicine and Health Sciences.

Dr. Villar is currently an Assistant Professor at the Department of Medicine, Division of Nephrology, of the University of Maryland, School of Medicine. His expertise is on renal physiology and biophysics and he has received advanced training in molecular cytogenetics and microarrays and on FRET-FLIM microscopy. He was a recipient of the Avery Research Scholar Award (equivalent to an NIH K1 Award) for his work on sorting nexin 1 at the Children’s National Medical Center.

Dr. Villar’s research interest is on the elucidation of the genetic underpinnings of essential hypertension and salt sensitivity using human renal epithelial cells and appropriate rodent models. He has published 20 papers in prestigious peer-reviewed journals and his work focuses on understanding the intricacies of dopamine receptor trafficking in proximal tubule cells as well as evaluating novel interacting and regulatory proteins. Many physiological processes are regulated by dynamic protein interaction networks whose characterization provides valuable information on cell biology and disease pathology. Identifying and characterizing these proteins provide a more comprehensive understanding of how these receptors work in the kidney. He was involved in the conceptualization and validation of novel delivery modes for siRNA into the kidney and the GI tract.

His current work centers mainly on several areas of research: (1) the role of GRK4 and its variants in the regulation of dopamine D3 receptor expression and function in human renal epithelial cells, (2) the dynamics of the interaction between select sorting nexins and several receptors, including the dopamine D5 receptor (a G protein-coupled receptor) and insulin receptor (a receptor tyrosine kinase) in the kidney to demonstrate the essential functions of sorting nexins in receptor trafficking and signal transduction, the loss of which may represent a novel mechanism for the development of hypertension, (3) the function of the protein phosphatase PP1 regulatory subunit GADD34 on D3R expression, trafficking, and function (a joint project with Dr. Maria João Pinho of the Faculdade de Medicina da Universidade do Porto, Portugal), and (4) the cross-regulation among the D1-like dopamine receptors and the α1A-adrenoreceptor.

Education and Training

  • 1989: B.S., Biology, University of the Philippines (Diliman)
  • 1993: M.D., Our Lady of Fatima University, College of Medicine
  • 2008: Ph.D., Molecular Biology and Biotechnology, University of the Philippines (Diliman)
  • 2004-2009: Post-doctoral Fellow, Georgetown University School of Medicine, Department of Pediatrics
  • 1998: 28th Wellcome Trust Advance Course, “Molecular Cytogenetics and Microarrays”, London, UK
  • 2009: 8th Annual Workshop on FRET Microscopy, W.M. Keck Center for Cellular Imaging, University of Virginia, VA, USA

Research Interests:

Human RPTCs
A collage of immortalized human renal proximal tubule cells obtained from Caucasian males showing the distribution and colocalization of G protein-coupled receptor 4 (GRK4, pseudocolored green) and the dopamine D3 receptor (pseudocolored red). The cells were labeled with a plasma membrane-impermeant biotin to delineate the cellular boundaries. The images were taken via laser scanning confocal microscopy. 600x magnification (VVillar)
Proximal tubules
Na+,K+-ATPase (pseudocolored magenta) internalizes into the cytoplasm of proximal tubule cells in the BALB/cJ mouse kidney treated with dopamine (2 mg/kg). Biotinylated Lotus tetragonolobus lectin was used to target the L-fucose found at the brush border (pseudocolored green) of renal proximal tubules. Wheat germ agglutinin and DAPI were used to visualize the plasma membrane and nuclei (pseudocolored red and blue, respectively). The composite image was taken via laser scanning confocal microscope. 600x magnification (VVillar)


Selected Journal Articles

Armando I, Wang X, Villar VA, Jones JE, Asico LD, Escano C, and Jose PA. Reactive Oxygen Species-dependent Hypertension in Dopamine D2 receptor-deficient Mice. Hypertension. 2007 Mar;49(3):672-8.

Pedrosa R, Villar VA, Pascua AM, Simão S, Hopfer U, Jose PA, Soares-da-Silva P. H2O2 stimulation of the Cl-/HCO3- exchanger by angiotensin II and angiotensin II type 1 receptor distribution in membrane microdomains. Hypertension. 2008 May;51(5):1332-8.

Li H, Armando I, Yu P, Escano C, Mueller SC, Asico L, Pascua A, Lu Q, Wang X, Villar VA, Jones JE, Wang Z, Periasamy A, Lau YS, Soares-da-Silva P, Creswell K, Guillemette G, Sibley DR, Eisner G, Felder RA, Jose PA. Dopamine 5 receptor mediates Ang II type 1 receptor degradation via a ubiquitin-proteasome pathway in mice and human cells. J Clin Invest. 2008 Jun 2;118(6):2180-2189.

Zeng C, Asico LD, Yu C, Villar VA, Shi W, Luo Y, Wang Z, He D, Liu Y, Huang L, Yang C, Wang X, Hopfer U, Eisner GM, Jose PA. Renal D(3) dopamine receptor stimulation induces natriuresis by endothelin B receptor interactions. Kidney Int.  74:750–9, 2008. (cover picture, subject of an editorial commentary).

Yang J, Cui Z, He D, Ren H, Han Y, Yu C, Fu C, Wang Z, Yang C, Wang X, Zhou L, Asico LD, Villar VA, Hopfer U, Mi M, Zeng C, Jose PA. Insulin increases D5 dopamine receptor expression and function in renal proximal tubule cells from Wistar-Kyoto rats. Am J Hypertens. 2009 Jul;22(7):770-6.

Villar VA, Jones JE, Armando I, Palmes-Saloma C, Yu P, Pascua AM, Keever L, Arnaldo FB, Wang Z, Luo Y, Felder RA, Jose PA. G protein-coupled receptor kinase 4 (GRK4) regulates the phosphorylation and function of the dopamine D3 receptor. J Biol Chem. 2009 Aug 7;284(32):21425-34.

Villar VA, Liu T, Jose PA. Recent trends in pediatric hypertension research. J Med Liban. 2010 Jul-Sep;58(3):179-84.

Zhang Y, Fu C, Asico LD, Villar VA, Ren H, He D, Wang Z, Yang J, Jose PA, Zeng C. Role of Gα(12)- and Gα(13)-protein subunit linkage of D(3) dopamine receptors in the natriuretic effect of D(3) dopamine receptor in kidney. Hypertens Res. 2011 Sep;34(9):1011-6.

Villar VA, Jones JE, Armando I, Asico LD, Escano CS Jr, Lee H, Wang X, Yang Y, Pascua-Crusan AM, Palmes-Saloma CP, Felder RA, Jose PA. Sorting nexin 1 loss results in D5 dopamine receptor dysfunction in human renal proximal tubule cells and hypertension in mice. J Biol Chem. 2012 Nov 14 (doi: 10.1074/jbc.M112.428458).

Villar VA, Armando I, Sanada H, Frazer LC, Russo CM, Notario PM, Lee H, Comisky L, Russell HA, Yang Y, Jurgens JA, Jose PA, and Jones JE. Novel Role of Sorting Nexin 5 in Renal D1 Dopamine Receptor Trafficking and Function: Implications for Hypertension. FASEB J. 2012 Nov 29 (doi:10.1096/fj.12-208439).

Yu P, Villar VA, Jose PA. Methods for the study of dopamine receptors within lipid rafts of kidney cells. Methods Mol Biol. 2013;964:15-24.

Book Chapter

Armando I, Villar VA, Jose PA. “Dopamine and renal function and blood pressure regulation” in Comprehensive Physiology. 1075–1117.