Jeffrey H. Miner, PhD, professor of medicine   Cover Illustration J Cell Sci 121:2008 (Miner Laboratory) George Jarad MD, instructor in medicine.

Highlights of research currently being conducted in the Division - including that by postdoctoral fellows - follows. Some of the investigators have primary appointments in other divisions within the Department of Internal Medicine or in other departments, reflecting the wide network of collaborative pursuits. George M. O'Brien Center: Washington University Center for Kidney Disease Research Between 1992-2003 (P50: Renal Genes, Growth Factors, Development and Disease) and again in 2007 [P30: The Center for Kidney Disease Research (CKDR)] the Washington University Renal Division was named recipient of a George M. O'Brien Center by NIDDK. The CKDR consists of an administrative core and three scientific cores; Renal Organogenesis Core; Renal Disease Models Core; and Kidney Translational Research Core. The first two are international in scope. The third is a regional St. Louis City-wide Core based at Washington University and including St. Louis University. The principal investigator for the Center is Dr. Marc Hammerman. To access the Washington University George M. O'Brien Center for Kidney Disease Research , please click on WU George M. O'Brien Center Frequent Hemodialysis Clinical Trials In 2003, the Washington University Renal Division was named a participating Center in the National Institutes of Health - sponsored study evaluating nocturnal hemodialysis, Frequent Hemodialysis Clinical Trials. The principal investigator for the Center is Dr. Brent Miller. Hemodialysis Vascular Access Clinical Trials Consortium In 2002, the Chromalloy American Kidney Center was named one of 5 participating Centers for the Hemodialysis Vascular Access Clinical Trials Consortium by the NIH. The Washington University Center will test the efficacy of dipyridamole as an agent to decrease the need for intervention and prolong the survival of PTFE grafts. Dr. James Delmez, medical director of the center, is the principal investigator. Drs. Daniel Coyne, Brent Miller, Marcos Rothstein and David Windus also participate.

Daniel W. Coyne, MD, professor of medicine, director of hemodialysis and outpatient clinics     Cover Story: Embryonic Donor Organs and Renal Organogenesis. Organogenesis 1:1 2004 (Hammerman laboratory)   Cover Illustration JASN 18:8:2007 (Miner Laboratory)

Institutional NIH Training Grants: Renal Disease In 1961 and again in 1974, the Division was awarded an institutional training grant by the NIH to prepare selected candidates for full-time careers in academic medicine. Since that time, the postgraduate education of a large number of physicians and renal scientists has been supported by this grant. Most trainees have remained in academic medicine and many have gone on to head renal divisions in the United States, Canada, Europe, and Asia or to assume other important academic scientific and administrative positions. Drs. Neal Bricker and Saulo Klahr have served as principal investigators for this award. Dr. Marc R. Hammerman is the present principal investigator. Renal Division-Biotechology Interactions Rarely has there been a time when universities and industry have sought closer alignment than today. The biotechnology revolution that has transformed and continues to change the landscape of health care began at the benches of university scientists. It became a reality, however, through partnerships with visionary companies that understood the enormous potential of biotechnology. The Renal Division interacts with a number of biotechnology companies through research agreements, licensing agreements and clinical trials. Transplantation of Developing Organs - Organogenesis of Kidney or Endocrine Pancreas Marc R. Hammerman, MD Human kidney or pancreas transplantation (or islet transplantation) is limited by organ availability. Use of porcine donors (xenotransplantation) is a possible alternative. One problem with the use in humans of developed porcine organs such as kidney or pancreas, is that humoral rejection is directed against antigens present on the vascular endothelium. Organ primordia (kidneys or pancreas) can be transplanted in 'cellular' form so that they develop in situ and become vascularized by the host obviating humoral rejection. If transplanted with its ureteric bud attached, a renal primordium (metanephros) transplanted into the mesentery enlarges and differentiates into a functional kidney that can maintain life for a time in otherwise anephric hosts following ureteroureterostomy between transplant and host. If transplanted at a sufficiently early stage of development, pancreatic primordia undergo selective endocrine differentiation post-transplantation such that exocrine components are not present at all. Embryonic pig pancreatic primordia transplanted into rats with type 1 (streptozotocin) or type 2 (ZDF) diabetes or into non-human primates with streptozotocin diabetes engraft and differentiate into functioning beta cells without the need for host immunsuppression. Glucose tolerance is normalized in rats with type 1 or type 2 diabetes within weeks after transplantation of pig pancreatic primordia.

Retro-peritoneal dissection of E15 rat embryo showing mesonephroi & metanephroi (Am. J. Physiol. 262:F523-F532, 1992)

Alex Brown, PhD, research associate professor Cover illustration, Kidney International 54:1, 1998 (Hammerman laboratory)   Cover illustration, Genomics 61:2, 1999 (Miner laboratory)   Cover illustration, Am. J. Physiology: Renal Physiology 48:1, 2000 (Hruska laboratory) David Ornitz MD PhD, Alumni endowed professor and chair, developmental biology

Vitamin D, Phosphate, and PTH Interactions in Health and Chronic Renal Failure Eduardo Slatopolsky, MD The major focus of our group is the evaluation of the factors involved in the pathogenesis of secondary hyperparathyroidism and bone disease in chronic renal failure. Our research examines the effect of dietary phosphate on the development of secondary hyperparathyroidism and, using the rat model of chronic renal failure, regulation of PTH secretion and pre-pro-PTH mRNA expression. In addition, new non-calcemic analogs of calcitriol are being investigated as regulators of PTH secretion and parathyroid gland growth in chronic renal failure. We are also interested in characterizing the mechanisms involved in the selective action of vitamin D analogs in vivo. The basic research in the field of secondary hyperparathyroidism is complemented by a series of clinical projects. Regulation of Renal Vitamin D Metabolism Alex J. Brown, PhD Activation of vitamin D occurs predominantly in the kidney. The active form of the vitamin, 1,25-(OH)2D3(calcitriol), is a hormone that binds to a cellular receptor similar to those for the steroid hormones. Calcitriol receptors have been found in more than two dozen tissues and mediate a variety of responses, but the most important actions of calcitriol are in the intestine, bone, kidney and parathyroid glands where it plays a critical role mineral homeostasis. There are several requirements for vitamin D analogs used in the treatment of secondary hyperparathyroidism. First, the analog has to have a reasonable affinity for the VDR. This requires the presence of a hydroxyl group in the 1[alpha] position. Second, the analog needs to be substantially less calcemic than the parent compound. Despite a high affinity for the VDR, many analogs have significantly less calcemic activity than 1,25-(OH)2D3. An example of this is 19-nor-1, 25-(OH)2D2, which is approximately 10 times less calcemic than 1,25-(OH)2D3. The decreased calcemic activity of 19-nor-1,25-(OH)2D2 cannot be attributed to decreased VDR binding. Finally, the analog has to be able to suppress PTH in vivo. Although some analogs are effective in suppressing PTH in vitro, when tested in vivo, they are rapidly metabolized and not effective in treating secondary hyperparathyroidism. Four analogs are currently used are 19-nor-1,25-(OH)2D2 (paricalcitol, Zemplar) and 1[alpha]-(OH)D2 (doxercalciferol, Hectorol), in the United States, and 22-oxa-calcitriol (OCT) and 1,25-(OH)2-26,27F6 D3 (falecalcitriol), in Japan. Fibroblast Growth Factor Expression and Action David Ornitz, MD, PhD Fibroblast growth factors (FGFs) are essential molecules for mammalian development. FGFs also are important regulators of angiogenesis, wound healing, and when inappropriately expressed, cancer. Engineered mutations in the genes encoding several FGFs and FGF receptors results in developmental defects and/or embryonic lethality in the mouse. FGF receptor 3 is expressed in developing bone, the central nervous system and in the organ of Corti of the inner ear. We have disrupted the gene encoding FGF receptor 3 in mice and have observed defects in both bone and inner ear development. We are studying the developmental role of FGF receptor 3 in this context. In a similar fashion, we have disrupted the gene encoding FGF-9. Preliminary data suggests a role in pulmonary and cardiac development. Currently we are analyzing the expression patterns of several new members of the FGF family.

2005 KIDNEY TRANSPLANTATION AT Barnes-Jewish Hospital/Washington University

Ahnan Usman MBBS, postdoctoral fellow   Brent W. Miller, MD, associate professor of medicine

Research in Renal Transplantation Daniel C. Brennan, MD The renal transplantation program is a mutual service between medicine and surgery. We collaborate closely with the other solid organ transplant programs such as liver, heart and lung, which provide sufficient patients for us to engage in both clinical and basic research. Our research efforts are in four main areas: 1) Viral infections in renal transplant patients-particularly cytomegalovirus (CMV) and polyomavirus (BK), 2) Induction immunosuppression, 3) Outcomes research using the USRDS, SRTR, and CMS database as well as our internal database, and human islet transplantation We also participate in several multicenter clinical trials of investigational immunosuppressive agents. Nocturnal (Frequent) Dialysis Modalities Brent W. Miller, MD The Frequent Hemodialysis Network trial will evaluate frequent or ‘nocturnal’ hemodialysis. We were one of the early adapters of nocturnal hemodialysis in the United States and one of the first to use a form called “single-needle nocturnal hemodialysis” which improves patient safety and acceptance of the dialysis procedure.

Anitha Vijayan, MD, associate professor of medicine     David Windus, MD, professor of medicine   Masato Hoshi PhD, postdoctoral fellow

Acute and Chronic Renal Failure and Transplantation Clinical Trials Anitha Vijayan, MD Acute kidney injury is the most common kidney-related problem in hospitalized patients, accounting for as many as 5% of hospitalizations. Mortality for this condition in patients remains high. We are conducting clinical trials to determine the best way to treat acute kidney injury in hospitalized patients. Daniel W. Coyne, MD Our research explores strategies to optimize management of anemia and secondary hyperparathyroidism in patients with chronic kidney disease while reducing costs. We have led and participated in multicenter trials demonstrating the efficacy and cost effectiveness of iron therapy in anemia management in dialysis and non-dialysis patients. Ongoing trials compare different erythropoiesis stimulating agents, and the longer term benefits, risks, and cost effectiveness of iron therapy in dialysis patients. We are also leading a multicenter trial exploring the efficacy and safety differences among different forms of active vitamin D in the treatment of secondary hyperparathyroidism. Medicine in Emerging Countries - Eritrea and Bhutan David W. Windus, MD Our work in Bhutan and Eritrea is conducted in conjunction with a team of nurses and diabetes educators and sponsored by Pathologists Overseas. The goals the Pathologists Overseas projects are improved physician education in management of chronic adult diseases and improved utilization of laboratory services. Specifically, we have developed productive working relationships with local physicians and other healthcare professionals, consulted on patients both in outpatient and inpatient settings, and organized continuing medical education courses for physicians in the areas of hypertension, diabetes, and kidney disease. We have evaluated the impact of the educational process on diabetes control in Eritrea. We demonstrated a significant improvement in diabetes control as evidence by a significant fall in hemoglobin A1C values. Our next project will be to further understand complications of diabetes in Eritrea by introducing urine microalbumin testing. The study will further expand knowledge about the prevalence of renal complications of diabetes in a new population but also allow for evidence-based interventions to slow the development of chronic kidney disease.

RET-mediated PLC-gamma activation ensures that only a single ureteric bud is formed.

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Feng Chen PhD, assistant professor of medicine

Calcineurin in the Development of the Excretory System Feng Chen, PhD Our laboratory studies the genetic determinants and the pathogenic mechanism of congenital anomalies of the kidney and the urinary tract (CAKUT). We have been using a variety of molecular genetic methods to create experimental and disease models to study the normal and abnormal development of the urinary tract with a specific focus on genes in the calcineurin/NFAT pathway. In addition, we have been using forward genetics methods to reveal the hereditary determinants of CAKUT. After the identification of the genetic mutation responsible for cph (congenital progressive hydronephrosis), we have been investigating other naturally occurring mutations causing CAKUT. We have also been developing new genetic tools, such as new tissue-specific Cre transgenes, for renal research. Another research area is in glomerular development and diseases. We have created conditional cell ablation or gene inactivation/activation models to study the pathogenesis of glomerulosclerosis. We are in the process of using a multi-disciplinary approach, including cutting edge genome technologies to study the molecular mechanism leading from defined genetic changes to the development of glomerulosclerosis.

FY 2005 NIH FUNDING

Stanley Misler, MD, PhD, associate professor of medicine   Alex Argoudeles MD, postdoctoral fellow Yinqui Wang PhD, postdoctoral fellow

Nephro-endocrinology Stanley Misler, MD, PhD Using single cells assays of exocytosis developed for neurobiology, we study aspects of stimulus-secretion coupling in several endocrine cells of particular importance to nephrology. In pancreatic islet beta cells, whose failure to secrete insulin is a major cause of chronic renal disease, we study the cellular basis of biphasic insulin secretion as well as cell-cell heterogeneity. In adrenal medullary chromaffin cells, whose hyperactivity contributes to secondary hypertension, we study of how acetycholine and latrotoxin stimulate slow exocytosis. In parathyroid chief cells, whose hyperactivity contributes to the musculoskeletal, CNS and cardiovascular sequelae of chronic kidney disease, with Alex Brown’s lab we study how reduction in extracellular [Ca2+] or enhancement of cytosolic [cAMP] triggers exocytosis of PTH granules. G protein signaling in renal ischemic injury Andrew Siedlecki MD G alpha-protein mediated signaling is a principal molecular pathway involved in ischemic renal injury. Regulators of G-protein Signaling (RGS) R4 subfamily stabilize the microvascular environment by diminishing intracellular effects of activated G-protein coupled receptors. Two members of the R4 subfamily, RGS2 and RGS4, interact with the G alpha subunit to modulate overstimulation of the vascular system. The goal of our laboratory is to understand the complementary roles of RGS2 and RGS4 in the renal vascular response to ischemia. Signal Transduction in Kidney and Bone Keith A. Hruska, MD The research focus of our laboratory is signal transduction in kidney, bone and endothelial cells. We have demonstrated that matrix proteins such as osteopontin when coupled to avb3 integrin, induce immediate cell signals such as activation of phosphatidylinositol 3-hydroxyl kinase and the proto-oncogene c-src. The regulation of the cytoskeleton through matrix protein/integrin interaction and cellular mechanical stimulation are current foci of activity in the laboratory. Another area under investigation is the role that bone morphogenetic protein 7 (BMP7) deficiency resulting from renal failure plays in the progression of kidney disease, disordered bone remodeling and susceptibility to vascular calcification. Using a rat model, we have determined that exogenously administered BMP 7 is broadly therapeutic in the setting of kidney disease.

Fused podocyte foot process in mice with a targeted mutation in the laminin beta 2 gene.

Vrinda Mahajan MBBS, postdoctoral fellow

Studies of Extracelular Matrix Jeffrey H. Miner, PhD My laboratory is interested in the role of basement membrane components in development, function, and disease of the kidney, with particular emphasis on the glomerular basement membrane (GBM). Several genetic and acquired diseases of the kidney affect the GBM, causing thinning or thickening. We are focusing on the laminin and type IV collagen components of the GBM and have identified a novel laminin chain that is present in all renal basement membranes. We have produced a set of "knockout" mice lacking this and other GBM components to determine their functions in the kidney and elsewhere. Some of these mutant mice serve as models for human diseases, including Alports syndrome and minimal change nephrotic syndrome.

The Developmental Consequences of RET Dysfunction in Kidney.

Sanjay Jain MD PhD, assistant professor of medicine and pathology   Cover Illustration Biol. of Reproduction 74:2:2006 (Jain Laboratory) Adriana Dusso, PhD, research associate professor Raphael Kopan, PhD, professor of molecular biology, pharmacology and medicine Jianghui Hou PhD, assistant professor of medicine.   Matt Coussens PhD, postdoctoral fellow

Role of RET in development and diseases of the urinary tract Sanjay Jain, MD, PhD The goal of my laboratory is to elucidate molecular signals that regulate early urogenital system development and delineate how they modulate renal regeneration after injury. Aberrations in these molecular signals may manifest as congenital renal and urinary tract abnormalities, one of the most common causes of renal failure in children, or severely compromise the ability of the kidney to overcome an acute or chronic insult. To this end we are currently investigating the roles of a neurotrophic growth factor, GDNF, and its receptor RET, a receptor tyrosine kinase. GDNF-RET signaling is crucial for renal development and is necessary for ureter maturation, ureteric bud induction and branching morphogenesis. These events rely on reciprocal interactions between the RET expressing ureteric bud epithelial cells that are also the precursors for the collecting ducts, and the GDNF expressing metanephric mesenchyme. Ongoing studies include determining the fate of RET-expressing cells in the kidney and testes, molecular aberrations due to defective RET pathways, role of RET associated pathways in acute injury and regeneration, and genetic abnormalities in CAKUT patients. Identifying how RET mediated signals regulate these diverse processes in kidney and ureter development will allow us to answer fundamental questions in renal development, understand pathogenesis of renal anomalies in patients and develop animal models of human kidney diseases. Regulation of Vitamin D Metabolism Adriana Dusso, PhD The focus of our research is the hyperplasia of secondary hyperparathyroidism, a common complication of kidney disease, which causes resistance to treatment with 1,25-dihydroxyvitamin D, and, consequently, high morbidity and mortality. We have identified the link between high growth rates and resistance to therapy: Enhanced parathyroid expression of transforming growth factor-alpha (TGF-alpha) and TACE (ADAM 17), the metalloproteinase that releases mature TGF-alpha from its trans-membrane precursor, generates a positive feed-forward loop sufficient to increase growth rates and suppress vitamin D receptor gene expression. Importantly, we find that 1,25-dihydroxyvitamin D suppresses TACE expression. The translational relevance of this finding extends beyond secondary hyperparathyroidism, as increased TACE-induced release of the soluble forms of TGF-alpha and the inflammatory molecules TNF-alpha, ICAM1 and VCAM1 from their precursors is known to cause inflammation in kidney and increase cardiovascular mortality in normal adults. We are defining the relationship between serum markers of TACE activity and renal and cardiovascular lesions and monitoring the efficacy of 1,25D inhibition of TACE to improve outcomes. Notch signaling in Kidney Raphael Kopan, PhD The Notch pathway regulates differentiation during development by mediating short range intercellular signals. Mutations resulting in partial loss of the Notch ligand, jagged 1, impact upon renal function (Alagille Syndrome). Our laboratory has developed a pharmacological approach for Notch loss in renal anlagen in order to identify Notch controlled transcriptional changes in the metanephric kidney. In addition we are using conditionally activatable Notch alleles coupled with organ culture methods to evaluate the nephrogenic potential of the mutants and test the hypothesis that constitutive Notch activation will alter the distribution of cell fates in metanephric blastema. Claudin 16 and claudin 19 function, interaction, and modulation of ion selectivity of tight junction Jianghui Hou, PhD The renal handling of magnesium and calcium in the thick ascending limb (TAL) of Henle’s loop is primarily through the paracellular pathway. Claudin-16 and claudin-19 are found in TAL of the nephron, and mutations in claudin-16 or 19 have been linked to the human hereditary disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). Our previous efforts have elucidated the channel functions of claudin-16 and claudin-19 (in epithelial cells such as MDCK and LLC-PK1), their interaction and synergy, and the in vivo role of claudin-16 in renal handling of magnesium and calcium. Continuing efforts to generate transgenic RNAi mouse models of claudin-19 and claudin-16/19 double knockdown will define the role of the TAL paracellular pathway in TAL ion and water homeostasis, define in vivo interaction and synergy between claudin-16 and -19 and provide a platform for drug screening.

Andrew Siedlecki MD, instructor in medicine Prashanth Podaralla MBBS MPH, postdoctoral fellow

Treatment of Resistant and Unconrolled Hypertension (Rheos Trial) Marcos Rothstein, MD Dr. Rothstein is Principal Investigator for the Rheos Trial for the treatment of resistant and uncontrolled hypertension. This study involves the implant of an electrical stimulator at the carotid baroreflex sinus. With the feasibility trial in its fourth year, most patients have achieved sustained reductions in systolic BP over 25 mm Hg, along with significant left ventricular function improvement. A large multi-center randomized trial is underway and CKD patient sub-studies are in the planning stage. Prevention of Complications in Patients with Chronic Kidney Disease James A. Delmez, MD Renal osteodystrophy is a universal complication of renal failure and is a major cause of morbidity in the 300,000 patients undergoing dialysis in the United States. High turnover bone disease (osteitis fibrosa) is the most common form of renal osteodystrophy and is due to excessive rates of parathyroid hormone (PTH) secretion. Complex abnormalities of calcium, phosphorus and calcitriol metabolism in renal failure stimulate PTH secretion. We are investigating the clinical utility of new compounds that bind phosphorus in the bowel to avoid hyperphosphatemia. We recently completed our participation as a lead clinical center in two NIH funded studies: the HEMO Study and the Dialysis Access Consortium (DAC) Study. In addition, we are assessing the factors involving in coronary, aorta, and carotid artery calcification in chronic hemodialysis patients and the effects of sodium thiosulfate on vascular function and structure in this population.

Andrey S. Shaw, MD, professor of pathology and immunology.

Congenital Nephrotic Syndrome in Mice Lacking CD-2 Associated Protein Andrey S. Shaw, MD CD2-associated protein (CD2AP) is an 80-kilodalton protein that is critical for stabilizing contacts between T cells and antigen-presenting cells. In CD2AP deficient mice, immune function is compromised. The mice die at 6 to 7 weeks of age from chronic renal failure. In the kidney, CD2AP is expressed primarily in glomerular epithelial cells. Knockout mice exhibit defects in epithelial podocytes, as well as mesangial cell hyperplasia and abnormal extracellular matrix deposition. Supporting a role for CD2AP in the slit diaphragm, CD2AP is associated with nephrin, the primary component of the diaphragm. Recently we have shown that mice heterozygous for CD2AP deficiency develop glomerular disease that is characterized by mesangial expansion and electron-dense deposits in subendothelial, subepithelial and mesangial locations. CD2AP heterozygous mice are also more susceptible to glomerular injury than their wild-type littermates.

Congenital hydronephrosis in mice with inactivation of calcineurin in the urinary tract.

Dwight Towler MD, PhD, professor of medicine   Nick Taraska, MD, postdoctoral fellow   Imran Memon MBBS, postdoctoral fellow Scott Boyle PhD, postdoctoral fellow Piyush Tripathi PhD, postdoctoral fellow   The BJC Institute of Health will open in 2009. It will house BioMed21.

Active Remodeling of Calcified Tissues Dwight Towler MD,PhD In the setting of type 2 diabetes mellitus (T2DM), lower-extremity musculoskeletal disease is prevalent, costly, and exceedingly difficult to manage, with fracture, arthropathy, ischemia, ulcer, infection, and amputation commonly confronting patients and clinicians. Aortofemoral medial artery calcification is a strong predictor of risk for lower extremity amputation in patients with T2DM. While not occluding the lumen, mural elastinolysis and medial calcification compromise arterial elasticity -- a material property necessary for Windkessel physiology that ensures normal tissue perfusion throughout the cardiac cycle. During diabetic arterial calcification, the Msx2-Wnt signaling cascade that controls orthotopic craniofacial bone formation is activated ectopically in the aortic valve and vessel wall. Diabetes and reactive oxygen species induce expression of Msx2 in arterial myofibroblasts, upregulate aortic Wnt gene expression, and activate pro-calcific and pro-fibrotic canonical Wnt signaling in the valve and tunica media. By studying Msx2 actions, we have identified that paracrine Wnt/Dkk signals control arteriosclerosis T2DM by regulating myogenic and osteogenic lineage allocation of vascular mesenchymal progenitors. Inflammatory redox cues initiated by TNF-alpha and osteopontin (OPN) modulate the activation of this arterial injury response, which appears to be sustained by myofibroblast mitochondrial dysfunction. We now study how strategies that manipulate aortic Wnt and OPN signaling regulate diabetic arteriosclerosis, arterial compliance (plethysmography), and lower extremity perfusion (LDPI) in murine models of diabetic vascular disease. St. Louis Children's Hospital Dr. Keith Hruska directs the Division of Pediatric Nephrology at Washington University and St. Louis Children's Hospital. Drs. Beck and Hmiel, also members of the Division, are interested in calcium metabolism and renal pharmacology respectively. The Division of Biology and Biomedical Sciences The Division of Biology and Biomedical Sciences (DBBS) was organized in 1973. DBBS is a graduate educational consortium that includes faculty affiliated with 20 basic science departments in the School of Medicine and the College of Arts and Sciences. DBBS programs are designed to provide a broad interdisciplinary approach to graduate education, emphasizing investigation of important questions in biology. Doctoral programs currently operating within the Division include: developmental biology, evolutionary and population biology, immunology, molecular biophysics, molecular cell biology and biochemistry, molecular genetics, molecular microbiology and microbial pathogenesis, neurosciences and plant biology. DBBS directs one of the largest and most successful Medical Scientist Training Programs offering a combined MD/PhD. BioMed 21 To any list of momentous dates in the history of life sciences at Washington University, 2003 must now be added as the year in which BioMed 21 was initiated. From the 1909 visit of Abraham Flexner that fueled a redefinition of American medical education through the completion of the Human Genome Project in 2002, few events will have the impact of BioMed 21. It is an intiative that will reshape university culture over the next decade to catalyze and support emerging forms of bioresearch and rapidly convert the knowledge of the genetic blueprint into effective individualized treatments for patients. As a first stage three new Institution-wide research units will be established: The Center for Genomics and Human Genetics; The Division of Clinical Sciences; and the Center for Biological Imaging. BioMed 21 is also a building program that will establish new spaces to house the emerging interdisciplinary basic and clinical research programs. Beginning in 2009, many BioMed 21 activities will take place in a new 250,000 square foot building, the BJC Institute of Health, that will serve as both a literal and figurative bridge between basic and clinical sciences on the Medical Campus.

Renal Division Department of Internal Medicine Washington University School of Medicine