Terry J. Watnick
Director Baltimore Polycystic Kidney Disease Research and Clinical Core Center
Dr. Terry Watnick is an Associate Professor of Medicine in the Division of Nephrology. She received her medical degree from The Yale School of Medicine and completed her Internal Medicine training at Yale-New Haven Hospital. She then moved to the Johns Hopkins Hospital where she received Clinical Training in Nephrology. She also completed a research fellowship that was focused on the genetics of autosomal dominant polycystic kidney disease. Dr. Watnick subsequently joined the faculty at the Johns Hopkins School of Medicine where she rose through the ranks to Associate Professor. During this time she continued to develop her clinical and research interests in Inherited Kidney Diseases. She moved to the University of Maryland School of Medicine in 2012 where she will continue to lead the Baltimore Polycystic Kidney Disease Research and Clinical Core Center (1P30 DK090868).
Fluorescence labeling of mature
Drosophila sperm with an
antibody to Fly Polycystin 2
(in green) shows that it is
expressed at the very tip of
Research in my laboratory focuses on understanding the biology of cystic kidney diseases. Autosomal dominant polycystic kidney disease (ADPKD) is the most common of these disorders and is caused by mutations in two genes PKD1 (proteins, polycystin-1) and PKD2 (protein-polycystin-2). ADPKD is a systemic disorder characterized by renal cysts, liver cysts and a number of vascular complications. We are using a variety of model systems/organisms to understand the biology of these proteins:
One project in the lab involves the use Drosophila melanogaster to dissect the molecules involved in ciliary trafficking of Polycystin-2. This is important because virtually all the protein products implicated in cystic diseases including have been found to localize to the primary cilia. Polcystins are conserved in Drosophila and play a key role in male fertility.
A second project focuses on the role of polycystins in endothelial cells and vascular smooth muscle cells. We are trying to understand why mutations in PKD proteins result in vascular phenotypes such as aneurysms in humans or edema and hemorrhage in mutant mice.
Baltimore Polycystic Kidney Disease Research and Clinical Core Center (1P30 DK090868):
- Hemorrhage (black arrows)
in a mouse embryo
The mission of the Baltimore Polycystic Kidney Disease Research and Clinical Core Center is to promote translational Polcystic Kidney Disease (PKD) research by providing unique resources and expertise to an international group of investigators. The Center is supported by a P30 grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). This is one of four such PKD Centers in the United States. Dr. Watnick serves as the Director of the Center and Dr. William Guggino (Chair of Physiology at the Johns Hopkins School of Medicine) is the Co-Director. The Center has 4 biomedical Research Cores:
- Antibody Validation and Vector Core (Director: Feng Qian, Ph.D.)
- Mouse Models and Biobank Core (Director: Dr. David Huso, D.V.M. Johns Hopkins School of Medicine)
- Cell Culture/Cell Engineering Core (Director: Erik Schwiebert, Ph.D., DiscoveryBioMed)
- Clinical/Translational Core (Director Terry Watnick, M.D., Co-Director, Stephen Seliger, M.D.)
Inherited kidney diseases including Autosomal Dominant Polycystic Kidney Disease, adult forms of autosomal recessive polycystic kidney disease, Alport syndrome, inherited glomerular diseases and Fabry disease. Dr. Watnick has established an inherited renal disease clinic at the University of Maryland that will continue to serve as a tertiary referral center for the mid-Atlantic Region. She has also been an investigator in several multicenter Clinical Trials recruiting patients with ADPKD, including TEMPO.
- Qian F*, Watnick TJ*, Onuchic LF, Germino GG. The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell 1996; 87:979-87. (*Co-authors, listed alphabetically, on title page).
- Watnick T, Phakdeekitcharoen B, Johnson A, Gandolph M, Wang M, Briefel G, Klinger KW, Kimberling W, Gabow P, Germino GG. Mutation detection of PKD1 identifies a novel mutation common to three families with severe disease. Am J Hum Genet 1999; 65:1561-71.
- Watnick T, He N, Wang K, Liang Y, Parfrey P, Hefferton D, St. George-Hyslop P, Germino G, Pei Y. Cyst formation in autosomal dominant polycystic kidney disease is a "Two-Hit" process that may result from trans-heterozygous mutations of interacting PKD proteins. Nat Genet 2000; 25:143-44.
- Watnick TJ, Jin Y, Matunis E, Kernan MJ, Montell C. A flagellar polycystin-2 homolog required for male fertility in Drosophila. Current Biology 2003; 13: 2179-84.
- Garcia-Gonzalez MA, Jones JG, Allen SK, Palatucci CM, Batish SD, Seltzer WK, Lan Z, Allen E, Qian F, Lens XM, Pei Y, Germino GG, Watnick TJ. Evaluating the clinical utility of a molecular genetic test for polycystic kidney disease. Mol Genet and Metab 2007; 92 160-7.
- Huang E, Samaniego M, McCune T, Melancon J, Montgomery R, Ugarte R, Kraus E, Womer K, Rabb H, Watnick T. DNA Testing for Live Kidney Donors at Risk for Autosomal Dominant Polycystic Kidney Disease. Transplantation 2009; 87: 133-37.
- Kashtan CE, Segal Y, Flinter F, Makanjuola D, Gan J-S, Watnick T. Aortic Abnormalities in Males with Alport Syndrome. Nephrol Dial and Transplant 2010;11:3554-60.
- Shah S, Watnick T, Atta MG. Not All Renal Cysts Are Created Equal. Lancet 2010; 376:1024.
- Garcia-Gonzalez MA, Outeda P, Zhou Q, Zhou F, Menezes LF, Huso DL, Germino GG, Piontek KB, Watnick T. Pkd1 and Pkd2 are Required in Trophoblasts and Endothelial Cells for Normal Placental Development. PLoS One 2010; 5(9): pii: e12821.
- Watnick T, Germino G. The role of mTOR inhibitors in autosomal dominant polycystic kidney disease. New Engl. J of Med. 2010; 363: 879-81.
- Kottgen M, Hofherr A, Li W, Chu K, Cook S, Montell C, Watnick T. Drosophila Sperm Swim Backwards in the Female Reproductive Tract and Are Activated via TRPP2 Ion Channels. PLoS One 2011; 6(5):e20031.
- Higashihara E, Torres VE, Chapman AB, Grantham JJ, Bae K, Watnick TJ, Horie S, Nutahara K, Ouyang J, Krasa HB, Czerwiec FS; TEMPO Formula and 156-05-002 Study Investigators. Tolvaptan in autosomal dominant polycystic kidney disease: three years experience. Clin J Am Soc Nephrol. 2011; 6: 2499-507.
- Pei Y, Lan Z, Wang K, Garcia-Gonzalez M, He N, Dicks E, Parfrey P, Germino G, Watnick T. A Missense Mutation in PKD1attenuates the severity of Renal Disease. Kidney Int 2012; 81:412-17.