Update Your ProfileAcademic Title:
Associate Professor
Primary Appointment:
Pharmacology & Physiology
Secondary Appointment(s):
Medicine
Additional Title:
Director of the Cell Culture and Engineering Core of the Baltimore PKD Research and Clinical Core Center
Location:
HSF3, 4110
Phone (Primary):
410 706 1760
Education and Training
University of Virginia, B.A. in Biology with Highest Distinction
University of Washington, PhD in Zoology
Johns Hopkins University School of Medicine, Research Fellow in Physiology
Research/Clinical Keywords
Uric Acid, Urate, Gout, Kidney, Renal Physiology, Polycystic Kidney Disease
Highlighted Publications
Yoshiharu Muto, Eryn E. Dixon, Yasuhiro Yoshimura, Haojia Wu, Chidambaram Ramachandran, Andrew J. King, Eric Olson, Marvin Gunawan, Jay Kuo, Jennifer Cox, Stephen L. Seliger, Owen M. Woodward, Paul A. Welling, Terry J. Watnick and Benjamin D. Humphreys (2022). Defining cellular complexity in human autosomal dominant polycystic kidney disease by multimodal single cell analysis. Nature Communications. Oct 30; 13:6497. doi:s41467-022-34255.
Mohammad Ikbal Choudhury, Yizeng Li, Panagiotis Mistriotis, Eryn E. Dixon, Jing Yang, Debonil Maity, Rebecca Walker, Morgen Benson, Leigha Martin, Fatima Koroma, Feng Qian, Konstantinos Konstantopoulos, Owen M. Woodward, Sean X. Sun (2022). Trans-epithelial Fluid Pumping Performance of Renal Epithelial Cells and Mechanics of Cystic Expansion. Nature Communications, Apr 28;13(1):2317. doi: 10.1038/s41467-022-29988-w.
Hoque KM, Dixon EE, Lewis RM, Allan J, Gamble GD, Phipps-Green AJ, Halperin Kuhns VL, Horne AM, Stamp LK, Merriman TR, Dalbeth N, Woodward OM. (2020) The ABCG2 Q141K hyperuricemia and gout associated variant illuminates the physiology of human urate excretion. Nature Communications. Jun 2;11(1):2767. doi: 10.1038/s41467-020-16525-w.
Dixon EE, Maxim DS, Halperin Kuhns VL, Lane-Harris AC, Outeda P, Ewald AJ, Watnick TJ, Welling PA, Woodward OM. (2020) GDNF drives rapid tubule morphogenesis in a novel 3Din vitromodel for ADPKD. Journal of Cell Science. Jun 8: jcs.249557.doi:10.1242/jcs.249557.
Adrienne Tin, Jonathan Marten, Victoria L. Halperin Kuhns, Yong Li, Matthias Wuttke, Holger Kirsten…Adriana M. Hung, Alexander Teumer, Cristian Pattaro, Owen M. Woodward†, Veronique Vitart, Anna Köttgen (2019) Target genes, variants, tissues and transcriptional pathways influencing human serum urate. (2019) Nature Genetics. doi:10.1038/s41588-019-0504-x (†Co-Senior Author).
Adrienne Tin, Yong Li, Jennifer Brody, Teresa Nutile, Audrey Chu, Jennifer Huffman, Qiong Yang, Ming-Huei Chen, Cassianne Robinson-Cohen, Aurélien Macé, Jun Liu, Ayse Demirkan, Rossella Sorice, Sanaz Sedaghat, Melody Swen, Bing Yu, Sahar Ghasemi, Alexander Teumer, Peter Vollenweider, Marina Ciullo, Meng Li, André Uitterlinden, Robert Kraaij, Najaf Amin, Jeroen van Rooij, Zoltán Kutalik, Abbas Dehghan, Barbara McKnight, Cornelia van Duijn, Alanna Morrison, Bruce Psaty, Eric Boerwinkle, Caroline Fox, Owen M. Woodward†, and Anna Köttgen (2018) Large-Scale Whole-Exome Sequencing Association Studies Identify Rare Functional Variants Influencing Serum Urate Levels. Nature Communications 2018 Oct 12;9(1):4228. (†Corresponding and Co-Senior Author).
Woodward, O.M. (2015) ABCG2: The Molecular mechanisms of urate secretion and gout. Am J Physiol Renal Physiol. 2015 Jul 1:ajprenal.00242.2015. doi: 10.1152/ajprenal.00242.2015.
Woodward, O.M.†, Tukaye, D.N., Cui, J., Greenwell P., Constantoulakis, L.M., Parker B.S., Rao, A., Kottgen, M., Maloney P.C., and Guggino, W.B. (2013) Gout causing Q141K mutation in ABCG2 leads to instability of the nucleotide binding domain and can be corrected with small molecules. Proc Natl Acad Sci USA. 110(13):5223-5228
Woodward, O.M., Kottgen, A., Coresh, J., Boerwinkle, E., Guggino, W.B., and Kottgen, M. (2009) Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proc Natl Acad Sci USA. 106(25):10338-42. PMCID: PMC2700910
Additional Publication Citations
Research Interests
My work has come to focus on the complicated workings of the human kidney and understanding how genetic mutations lead to disease, describing the physiological mechanism, and finding possible therapies.
ABCG2, Hyperuricemia, and gout
Urate (uric acid) handling and secretion in humans and the great apes is unique among mammals; we have lost the function of the urate oxidase (uricase) enzyme, the enzyme responsible for metabolizing urate into allantoin. The loss of uricase appears to be adaptive in humans, however it puts humans at risk for retaining too much urate (hyperuricemia), which can lead to gout, kidney disease, hypertension, metabolic disorders and cardiovascular disease. Yet, until recently the transporters responsible for urate secretion and absorption remained mostly unknown.
We discovered that ABCG2 is a novel urate transporter, perhaps the most important secretion mechanism for uric acid in humans, and identified a loss of function mutation that causes hyperuricemia and gout. Importantly the mutation is common, carried by almost a billion people, putting them at increased risk for hyperuricemia, gout, and possibly hypertension and other metabolic diseases. Most recently, we have gained an understanding of how this mutation causes dysfunction in ABCG2 and have used this new understanding to find small molecules that can correct the defect, a proof of principal that new small molecule therapy may be possible for hyperuricemia and gout.
Polycystic Kidney Disease
Inheritance of polycystic kidney disease genes causes slow growing kidney cysts with severe consequences for kidney function. Study of disease causation is often obscured by the later stages of a multistage disease process. Our lab focuses on the first stage of ADPKD, cystogenesis, and on the first protein changes that occur upon acute loss of the PKD2 disease gene and protein product PC2. We use a new ex-vivo 3D culture method to grow epithelial kidney tubes to investigate what happens to the nephrons as they transform into cysts with the loss of PKD2. Discovery of the initial steps of cystogenesis after PKD2 loss may illuminate precise drugable targets for the development of future PKD therapeutics.
Lab Techniques and Equipment
Our work uses many different tools, all focused on understanding the physiology of the human kidney. We use genetic studies to find disease causing mutations and test the mutant protein’s function with radioactive transport assays, patch clamp studies, two electrode voltage clamp, live cell imaging, and FRET. And finally we use mouse models to gain a better understanding of how mutant proteins fit into the whole animal physiology.