Tomoko Obara

Assistant Professor, Department of Cell Biology      


EDUCATION

Ph.D., Pharmacy, Tokyo University

MEMBERSHIPS

Society of Developmental Biology
American Society of Nephrology
FASEB
American Journal of Physiology
 

RESEARCH SUMMARY

My long-term research interest is to investigate kidney development in zebrafish, medaka, and mouse models with a view toward using them as model organisms for human chronic kidney diseases, such as diabetic nephropathy and ciliopathy.


 
Project 1: Developing a kidney stem cell to repair renal diseases

In the U.S., diabetes is the most common cause of chronic kidney disease and progresses to end-stage renal disease that requires dialysis or a kidney transplant. Kidney transplantation is a better long-term option for treatment, but typically requires a long wait for matched organs along with continued immunosuppressive therapy. Therefore, there is a critical need for new therapeutic approaches to preserve kidney function. Multipotent kidney cells may be a valid new therapeutic approach to repair and regenerate functional kidneys. Despite the successful derivation of pluripotent stem cells for various organs, the kidney has remained a major challenge for regenerative medicine. We developed, for the first time, a multipotent mouse adult kidney cell line that expresses renal progenitors as well as multiple adult kidney cell types. Moreover, we discovered that engrafted multipotent mouse adult kidney cells are capable of developing in immunocompromised adult medaka kidneys (mesonephros) and these cells express multiple types of adult mouse kidney cell markers and renal progenitors. Our long-term goal is to develop models that provide insights into the treatment of diabetic nephropathy and ciliopathies.

 

Project 2: Developing a new diabetic nephropathy and ciliopathy models to study chronic kidney disease

Hyperglycemia is a manifestation of diabetes and leads to diabetic nephropathy. Diabetic nephropathy progresses to chronic kidney disease and then to end-stage renal disease that requires dialysis or kidney transplant. Despite this growing public health problem, there are substantial hurdles to studying kidney pathological mechanisms and testing therapies that slow down progressive disease. One major obstacle to the identification and evaluation of novel therapies is the paucity of animal models that faithfully recapitulate human disease. Recent advances have created better vertebrate models of diabetes using genetic mutations, manipulation of diet, or pharmacological agents. We established new medaka, mouse, and rat models, including a medaka model that mimics human diabetic nephropathy, to examine regenerative therapies for this disease. This medaka model system has multiple advantages over other animal models because it permits us to perform rapid screening to identify the major factors involved in nephropathy. The identification of highly specific targets should open up new therapeutic approaches to preserve kidney function in patients who have diabetes.

 

Project 3: Glomerular development and chronic kidney disease

The glomerulus exhibits a common structural organization among vertebrates. Ultrafiltration of plasma in the renal glomeruli is a major function of the kidneys. The glomerular filtration barrier, which is responsible for the size and charge-selective properties of the filter, comprises a fenestrated endothelium, the glomerular basement, and podocytes, which are highly specialized epithelial cells within the kidney. Glomerular diseases are primarily responsible for chronic kidney disease and end-stage renal disease. The slit diaphragm is a highly specialized intercellular junction between podocytes’ foot processes and plays a crucial role in the formation of the filtration barrier in the renal glomeruli. Because of its molecular complexity, the podocyte slit diaphragm protein machinery represents a main target for both acquired and genetic diseases of the filtration barrier. Although slit diaphragm proteins have been identified, their involvement in the formation and maintenance of a healthy slit diaphragm and in the molecular etiology of disease is unknown. Our work will be the first to systematically utilize a multi-disciplinary approach combining the use of zebrafish and medaka genetics, proteomics, and biochemical approaches to characterize how slit diaphragm protein mutations affect slit diaphragm function. Our study will provide the foundation to identify potential therapeutic targets for ameliorating kidney failure.

 


SELECTED PUBLICATIONS
 

Webb, C.F.**, Ratliff*, M.L., Powell*, R., Wirsig-Wiechmann, C.R., Lakiza, O. and Obara, T**. (*Shared first-author, **corresponding authors) (2015) A developmentally plastic mouse kidney cell line spontaneously generates multiple adult kidney structures. Biochem Biophys Res Commun. doi: 10.1016/j.bbrc.2015.06.130. Epub 2015 Jun 23. PMCID: PMC26111446

 

Walter, R. B. and Obara, T. (2015) Workshop Report: The Medaka Model for Comparative of Human Disease Mechanisms. Comp Biochem Physiology C Toxicol Pharmacol.  doi:10.1016/j.cbpc.2015.06.003. Epub 2015 Jun 19. PMCID: PMC26099189

 

Fukuyo, Y., Nakamura, T., Bubenshchikova, E., Powell, R., Tsuji, T., Janknecht, R., & Obara, T. (2014) Nephrin and Podocin functions are highly conserved between the zebrafish pronephros and mammalian metanephros, Molecular Medical Report, 9 (2), 457-465. PMID: PMC24337247

 

Ichimura, K., Powell, R., Nakamura, T., Kurihara, H., Sakai, T., and Obara, T. (2013) Podocalyxin regulates pronephric glomerular development in zebrafish. Physiol Rep. 1 (3), e00074. PMID: PMC24224085. Selected as an editor’s choice.

 

Ichimura, K.*, Kawashima, Y.*, Nakamura, T.*, Powell, R., Hidoh, Y., Terai, S., Sakaida, I., Kodera, Y., Tsuji, T., Ma, J-x., Sakai, T., Matsumoto, H., & Obara, T. (*First-author shared) (2013) Medaka fish, Oryzias latipes, as a model for human obesity-related glomerulopathy, Biochem Biophys Res Commun. 341 (4), 712-717. PMID: PMC23353086. Cited in World Biomedical Frontier [ISSN: 2328-0166], 2013.

 

Ichimura, K., Fukuyo, Y., Nakamura, T., Powell, R., Sakai, T., Janknecht, R., & Obara, T. (2013) Developmental localization of Nephrin in zebrafish and medaka pronephric glomerulus. J. Histochem Cytochem. 61 (4), 313-324. PMID: PMC23324868. Selected in Pub Advanced.

 

Ichimura, K., Fukuyo, Y., Nakamura, T., Powell, R., Sakai, T., & Obara, T. (2012). Structural disorganization of pronephric glomerulus in Zebrafish mpp5a/nagie oko mutant. Dev Dyn. 241 (12), 1922-1932. PMID: PMC23027442, Cited in Global Medical Discovery [ISSN 1929-8536], 2012.

 

Ichimura, K., Bubenshchikova, E., Powell, R., Hsu, C., Fukuyo, Y., Tran, U., Tanaka, M., Oda, S., Wessely, O., Kurihara, H., Sakai, T., & Obara, T. (2012). A comparative analysis of glomerulus development in the pronephros of medaka and zebrafish. PLoS One, 7 (9), e45286. PMID: PMC23028906.

 

Bubenshchikova, E., Ichimura, K., Fukuyo, Y., Powell, R., Hsu, C., Morrical, S. O., Sedor, J. R., Sakai, T., & Obara, T. (2012). Wtip and Vangl2 are required for mitotic spindle orientation and cloaca morphogenesis Biology Open, 1 (6), 588-596. PMID: PMC23213452.

 

Kim, J., Zaghloul, N. A., Bubenshchikova, E., Oh, E. C., Rankin, S., Katsanis, N., Obara, T., & Tsiokas, L. (2011). Nde1-mediated inhibition of ciliogenesis affects cell cycle re-entry. Nat Cell Biol. 13 (4), 351-360. PMID: PMC21394081.

 

Giamarchi, A., Feng, S., Rodat-Despoix, L., Xu, Y., Bubenshchikova, E., Newby, L. J., Hao, J., Gauioso, C., Crest, M., Lupas, A. N., Honore, E., Williamson, M. P., Obara, T., & Ong, A. C., & Delmas, P. (2010). A novel polycystin-2 dimerization domain essential for polycystin-1 recognition and function of polycystin complexes. EMBO J., 29 (7), 1176-1191. PMID: PMC20168298.

 
 

MAILING ADDRESS
Dept. of Cell Biology
University of Oklahoma Health Sciences Center
940 Stanton L. Young Blvd., BMSB 782
Oklahoma City, OK 73104-5020
Office (BMSB 782) phone: (405) 271-2377 ext. 47035
Lab (BMSB 781 & 753B) phone: (405) 271-2377 ext. 47967
Fish room (BMSB 114 and 116) phone: (405) 271-8001 ext. 30461
Fax: (405) 271-3548
tomoko-obara@ouhsc.edu