Mission and themes. This is an application for renewal of a George M. O'Brien Kidney Research Core Center at the University of Texas Southwestern Medical Center at Dallas currently directed by Dr. Orson Moe who is Professor of Internal Medicine and Physiology, and Chief of the Division of Nephrology at UT Southwestern. The overall mission of the Center is to promote bidirectional synergistic interactions between basic scientists and clinical researchers, maximally optimize research for renal investigators, and encourage and facilitate non-renal researchers to study renal questions. Our three main themes are: 1. Kidney development and genetics. 2. Physiology and pathophysiology. 3. Chronic kidney disease and its complications Need for Center. Discoveries in renal science is emerging at an alarming rate and from diverse circumstances. No single laboratory or investigator can take their findings through development into full biologic elucidation and eventual clinical applications. Researchers outside the renal field often make interesting findings pertinent to kidney disease but lack the ability to pursue the finding due to lack of knowledge, reagents, models, and techniques. This gap needs to be bridged so opportunities of discovery will not be missed, and we can also increase the number of renal investigators. Within the renal research community, basic scientists need appropriate and extensive phenotyping, to translate their findings to clinical application. Clinical researcher also need bench clarification of clinical findings to elucidation mechanisms, and robust systems to discover new biomarkers and treatment. Bidirectional translation is a central purpose of our Center. Our ultimate goal is to improve diagnosis and treatment of kidney diseases. Number of Center Members and Direct Cost. Our Center houses 12 Center Members, which are UT Southwestern faculty holding a title within and directly supported by the O'Brien Center. We have 254 Core Members, who are on or off campus users of the O'Brien Center. The direct cost requested is about $749,000 per year. The Center is subsidized by the Renal Division and by UT Southwestern so the real operating cost actually exceeds the allowed budget. Overview of research base, Biomedical Cores, P&F Program and Enrichment Program. The Center supports all research with some relationship to kidney function and disease. Many basic scientists work on highly fundamental biologic problems such as atherosclerosis, autophagy, cellular protein trafficking, diabetes, find scientific merit in using the kidney as model systems and we are delighted that we can attract such investigators to renal investigation. We fulfil our role via three portals- infrastructure support, education, and fiscal support to jumpstart pilot projects. Biomedical Research Cores. Four Cores are designed to provide the infrastructure to bridge the full span for bidirectional translation. (A) The Animal Core distributes and helps generate genetically modified mice as well as create disease models for full phenotyping by two other Cores. (B) The Physiology Core provides functional phenotyping enabling the study of a wide variety of whole organism function. (C) Cell Biology, Pathology, and Imaging Core supports anatomic and functional phenotyping from the whole organism to the single cell. (D) The Clinical Translational Core facilitates bidirectional translation of findings to fulfil our objective. Enrichment Program. We provide education through several means. We have a bimonthly seminar series with lecturers on campus as well as invited speakers to cover many aspects of kidney function and disease. In addition, we have an annual Symposium where specific topics are covered by leading experts in the field. Our Biomedical Cores also provide theoretically and technical training to investigators. Finally, our O'Brien Center hosts several summer projects to educate and motivate students to enter renal research. Pilot and Feasibility Program. In the preliminary phase of hypothesis testing, investigators frequently do not have adequate data for extramural grant application. Our P&F program funds two grants from junior investigators or senior investigators considering an excursion from their trajectory to venture into kidney research. We have an excellent track record of previous grantees submitting and obtaining grants. The mechanisms outlined serves a large body of investigators in the US and abroad to make advances in kidney development and genetics, physiology and pathophysiology, and chronic kidney disease, to advance the diagnosis and treatment of human kidney disease.
Kidney disease has reached epidemic proportions in the USA ad globally imparting negatively on health and causing many deaths but unfortunately, progress in diagnosis and treatment while existent and has progressed, remained very slow and limited. This Center plans to facilitate the research of kidney scientists and attract other scientists to enter kidney research via three avenues of an education program to disseminate and enhance knowledge, a pilot grant program that help jumpstart small pilot projects to gather momentum, and finally offer our biomedical cores service that will assist all kidney researchers to conduct animal experiments and translate them into human studies. We expect the efforts of the Center to improve our ability to diagnose and treat human kidney disease to relieve suffering and health care burden via education and research.
|Raman, Archana; Reif, Gail A; Dai, Yuqiao et al. (2017) Integrin-Linked Kinase Signaling Promotes Cyst Growth and Fibrosis in Polycystic Kidney Disease. J Am Soc Nephrol 28:2708-2719|
|Yano, Yuichiro; Neeland, Ian J; Ayers, Colby et al. (2017) Hemodynamic and Mechanical Properties of the Proximal Aorta in Young and Middle-Aged Adults With Isolated Systolic Hypertension: The Dallas Heart Study. Hypertension 70:158-165|
|Hajarnis, Sachin; Lakhia, Ronak; Yheskel, Matanel et al. (2017) microRNA-17 family promotes polycystic kidney disease progression through modulation of mitochondrial metabolism. Nat Commun 8:14395|
|Van Buren, Peter Noel (2017) Pathophysiology and implications of intradialytic hypertension. Curr Opin Nephrol Hypertens 26:303-310|
|Pan, Xinchao; Karner, Courtney M; Carroll, Thomas J (2017) Myc cooperates with ?-catenin to drive gene expression in nephron progenitor cells. Development 144:4173-4182|
|Wang, Qian; Cobo-Stark, Patricia; Patel, Vishal et al. (2017) Adenylyl cyclase 5 deficiency reduces renal cyclic AMP and cyst growth in an orthologous mouse model of polycystic kidney disease. Kidney Int :|
|Sanghera, Prateek; Ghanta, Mythili; Ozay, Fatih et al. (2017) Kidney Diseases Associated With Alternative Complement Pathway Dysregulation and Potential Treatment Options. Am J Med Sci 354:533-538|
|Kim, Ji-Hee; Xie, Jian; Hwang, Kyu-Hee et al. (2017) Klotho May Ameliorate Proteinuria by Targeting TRPC6 Channels in Podocytes. J Am Soc Nephrol 28:140-151|
|Wu, Yueh-Lin; Xie, Jian; An, Sung-Wan et al. (2017) Inhibition of TRPC6 channels ameliorates renal fibrosis and contributes to renal protection by soluble klotho. Kidney Int 91:830-841|
|Ku, Elaine; Gassman, Jennifer; Appel, Lawrence J et al. (2017) BP Control and Long-Term Risk of ESRD and Mortality. J Am Soc Nephrol 28:671-677|
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