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Owen M. Woodward, PhD

Academic Title:

Assistant Professor

Primary Appointment:

Physiology

Additional Title:

Co-Director of the Cell Culture and Engineering Core of the Baltimore PKD Research and Clinical Core Center

Location:

HSFI, Room 565

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, Gout, Kidney, Renal Physiology, Polycystic Kidney Disease

Highlighted Publications

EE Dixon and OM Woodward(2018) Three dimensional invitro models answer the right questions in ADPKD cystogenesis. Am J Physiol Renal Physiol PMID 29693448.

Cleophas MC, Joosten LA, Stamp LK, Dalbeth N, Woodward OM, and Merriman, TR (2017) ABCG2 polymorphism in gout: insights into disease susceptibility and treatment approaches. Pharmgenomics Pers Med. Apr 20; 10:129-142

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 moleculesProc Natl Acad Sci USA. 110(13):5223-5228 (†Corresponding Author)

Anna Köttgen, Eva Albrecht, Alexander Teumer, Veronique Vitart, Jan Krumsiek, Claudia Hundertmark, Giorgio Pistis, Daniela Ruggiero, Conall M O’Seaghdha, Toomas Haller, Qiong Yang, Toshiko Tanaka, Andrew D Johnson, Zoltán Kutalik, Albert V Smith, Julia Shi, Maksim Struchalin, Rita PS Middelberg, Morris J Brown, Angelo L Gaffo, Nicola Pirastu, Guo Li, Caroline Hayward, Tatijana Zemunik, Jennifer Huffman, Loic Yengo, Jing Hua Zhao, Ayse Demirkan, Mary F Feitosa, Xuan Liu, Giovanni Malerba, Lorna M Lopez, Pim van der Harst, Xinzhong Li, Marcus E Kleber, Andrew A Hicks, Ilja M Nolte, Asa Johansson, Federico Murgia, Sarah H Wild, Stephan JL Bakker, John F Peden, Abbas Dehghan, Maristella Steri, Albert Tenesa, Vasiliki Lagou, Perttu Salo, Massimo Mangino, Lynda M Rose, Terho Lehtimäki, Owen M. Woodward, Yukinori Okada, et al. (2013) Genome-wide association analyses identify 18 new loci associated with serum urate concentrationsNature Genetics. 45(2): 145-54.

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 goutProc 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.

Recently, 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.

Links of Interest