Thu Le, MD
Associate Professor of Medicine
MD: George Washington University
434-982-1063 | Fax 434-924-5848 | email@example.com
Funded by an RO1 on Genes That Regulate Progression of Kidney Disease and Its Cardiovascular Effects.
The primary focus of my laboratory is on genetic susceptibility to vascular injury and chronic kidney disease. We use mouse models of human diseases, and take advantage of naturally occurring strain differences in susceptibility to disease for gene mapping, with the goal of candidate gene identification and validation. For example, using a genetic sensitizer in a mouse model of renal vascular injury, we recently identified Gstm1 gene as a candidate modifier gene that regulates susceptibility to vascular injury. Through in vitro functional characterization, we uncovered that Gstm1 regulates vascular smooth muscle cell proliferation and migration, likely through its role in handling oxidative stress. Our ultimate goal is to perform translational studies to test the effects of genetic variants of our candidate genes in human disease in carefully selected human cohorts.
My clinical interests include hypertension, chronic kidney disease, and acute renal failure.
Yang Y, Parsons KK, Chi L, Malakauskas SM, Le TH. Glutathione-S-Transferase µ 1 regulates vascular smooth muscle cell proliferation, migration and oxidative stress. Hypertension, in print Dec 2009. Epub October 12, 2009.
Branagan NM, Higgins SP, Halim SA, Le TH. Systemic polyarteritis nodosa mimicking pyoderma gangrenosum in a rare manifestation of small/chronic lymphocytic leukemia. Clin Exp Derm. 2009;34(5):e127-129.
Malakauskas SM, Kourany WM, Lu DH, Hohmeier HE, Stevens RD, Koves TR, Muoio DM, Newgard CB, Le TH. Increased insulin sensitivity in mice lacking collectrin, a downstream target of HNF-1. Mol Endo. 2009;23(6):881-892.
Yasuhara A, Wada J, Malakauskas SM, Zhang Y, Eguchi J, Nakatsuka A, Murakami K, Kanzaki M, Teshigawara S, Yamagata K, Le TH, Makino H. Collectrin is involved in the development of salt-sensitive hypertension by facilitating the membrane trafficking of apical membrane proteins via interaction with SNARE complex. Circulation. 2008;118(21):2146-2155.
Gembardt F, Heringer-Walter S, va Esch JHM, Sterner-Kock A, van Veghel R, Le TH, Garrelds IM, Coffman TM, Jan Danser AH, Schultheiss HP, Walther T. Cardiovascular phenotype in mice lacking all three subtypes of angiotensin II receptors. FASEB J. 2008;22:3068-3070.
Le TH, Coffman TM. Targeting genes in the renin-angiotensin system. Curr Opin Nephrol Hypertens. 2008;17(1):57-63.
Salzler HR, Griffiths R, Ruiz P, Chi L, Frey C, Marchuk DA, Rockman HA, Le TH. Hypertension and albuminuria in chronic kidney disease mapped to a mouse chromosome 11 locus. Kidney Int. 2007;72:1226-1232.
Crowley SD, Gurley SB, Herrera MJ, Ruiz P, Griffiths R, Kumar AP, Kim HS, Smithies O, Le TH, Coffman, TM. Hypertension and cardiac hypertrophy are mediated by angiotensin receptors in the kidney. PNAS. 2006;103(47):17985-90.
Malakauskas SM, Quan H, Fields TA, McCall SJ, Yu MJ, Kourany WM, Frey CW, Le TH. Aminoaciduria and altered renal expression of luminal amino acid transporters in mice lacking novel gene collectrin. Am J Physiol Renal Physiol. 2007;292(2):F533-44.
Gurley SB, Allred A, Le TH, Griffiths R, Mao L, Phillip N, Haystead TA, Donoghue M, Breitbart RE, Acton SL, Rockman HA, Coffman TM. Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice. J Clin Invest. 2006;116:2218-2225.
Le TH, Coffman TM. A new cardiac MASTer switch for the renin-angiotensin system. J Clin Invest. 2006;116(4):866-869.