Research Updates in Kidney and Urologic Health

KUH Plans Programs for 2002

Through its Division of Kidney, Urologic, and Hematologic Diseases (KUH), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) provides leadership for a national research program in kidney and urologic diseases. Each year, KUH works with NIDDK's National Advisory Council, which represents a broad range of non-Federal scientific, educational, and medical institutions, to plan and develop a set of program initiatives designed to yield fundamental, innovative, and valuable contributions to human health. The following list of KUH initiatives and programs for 2002 demonstrates the division's commitment to maintaining the phenomenal progress of recent years in understanding the biological processes that lead to kidney and urologic diseases. The initiatives also demonstrate a continuing commitment to clinical research, epidemiology, and training.

Requests for Applications (RFAs)

Focal segmental glomerulosclerosis (FSGS) is a common, irreversible process that results in steroid-resistant nephrotic syndrome. It often appears as a primary condition, with a propensity for progression to end-stage renal disease (ESRD), and recurs after transplantation in children, resulting in injury to or loss of the new kidney. The peak incidence is in the preschool years, with boys more often affected than girls. The worst prognosis is observed in African-American children.

The overall goal of the proposed initiative is to test the value of selected immunosuppressive interventions, with converting enzyme inhibitors as an adjuvant intervention, for preventing the progression of FSGS in children and young adults. A prospective, randomized, multicenter clinical trial examining the impact of immunomodulatory therapy on proteinuria is proposed. The sample size needed is estimated at approximately 300 patients enrolled over a 3-year period and followed for approximately 24 months. If the clinical trial is successful, the results will guide physicians in providing the safest and most effective care for children with FSGS.

Letter of Intent Receipt Date: February 15, 2002
Application Receipt Date: March 15, 2002
To view the full RFA for this program, go to grants.nih.gov/grants/guide/rfa-files/RFA-DK-02-013.html on the Internet.

For more information or clarification, contact
Gladys Hirschman, M.D.
Director, Chronic Renal Diseases and Pediatric Nephrology Programs
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 609
MSC 5458
Bethesda, MD 20892–5458
Phone: 301–594–7717
Fax: 301–480–3510
Email: hirschmang@ep.niddk.nih.gov

The NIDDK seeks applications for studies to test new strategies for preventing or treating diabetic nephropathy. Large-scale interventional trials have established that blockade of the renin-angiotensin system (RAS) and good glycemic control both slow the progression of diabetic nephropathy. Nonetheless, many patients with diabetes develop progressive renal disease despite adequate management, and new strategies, both to prevent the disease and to slow its progression, are urgently needed.

The NIDDK has issued an RFA inviting clinical research applications for trials using novel agents or drug combinations to prevent the onset or slow the progression of diabetic nephropathy. The goal of this initiative is to evaluate therapies that might potentially progress to large phase 3 interventional trials. In the pilot phase, using measurements of urinary protein, either albumin or total protein, as a surrogate marker for disease progression is appropriate. Unless otherwise indicated, control and trial group members with proteinuria will be treated with RAS blockade as the current standard of care, and the studies will examine either the addition of alternative agents or the incremental effects of RAS blockade. Enrollment strategies should emphasize a patient population in young- to mid-adulthood and have strong representation of patients with type 1 diabetes. If indicated, assessment of the impact of the intervention on retinopathy or neuropathy could be incorporated into the trial design.

Letter of Intent Receipt Date: January 17, 2002
Application Receipt Date: February 14, 2002
To view the full RFA for this program, go to grants.nih.gov/grants/guide/rfa-files/RFA-DK-02-025.html on the Internet.

For more information or clarification, contact
Thomas Hostetter, M.D.
Senior Scientific Advisor
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 625
MSC 5458
Bethesda, MD 20892–5458
Phone: 301–594–8864
Fax: 301–480–3510
Email: hostettert@extra.niddk.nih.gov

Prevention and treatment of long-term complications remain a critical problem in the management of type 1 and type 2 diabetes. In the United States, diabetes is the leading cause of new blindness in working-age adults, of nontraumatic lower leg amputations, and of new cases of ESRD. Diabetes has been estimated to cost the U.S. economy over $98 billion annually, much of it related to the treatment of long-term micro- and macrovascular complications.

Identifying patients at risk for the development of complications, with the hope of early intervention, is a public health priority. Early intervention is essential, because irreparable structural organ damage may already have occurred by the time symptoms are recognized.

Diabetic nephropathy accounts for approximately 45 percent of new cases of ESRD. Major risk factors for the development of diabetic nephropathy include duration of diabetes and poor metabolic control. However, the incidence of nephropathy demonstrates considerable ethnic/racial variability, and not all patients with prolonged hyperglycemia develop ESRD, thus suggesting a strong genetic component to susceptibility. For renal disease, microalbuminuria is the best available noninvasive predictor of the risk of diabetic nephropathy, but it is not a precise indicator. Screening for microalbuminuria is considered a "standard of care," and treating patients who have microalbuminuria with angiotensin-converting enzyme (ACE) inhibitors often slows the progression to overt proteinuria and renal disease. More data are needed to delineate the extent to which increases in microalbuminuria predict either pathologic progression or ultimate progression to ESRD. In addition, some patients whose microalbuminuria has not increased may nonetheless develop advanced renal lesions. Finally, prevention strategies might be most effective for patients with normal albumin excretion, if those at high risk for the development of nephropathy could be identified before microalbuminuria develops.

The NIDDK has issued an RFA inviting basic and clinical research applications to develop biochemical, cellular, physiologic, or genetic surrogate endpoints that can be used to predict risk, aid in early diagnosis, and assess progression of the microvascular complications of diabetes. The overall goal of this RFA is to develop biomarkers that could be used as diagnostic tools for the individual patient or as outcome measures to be used in clinical trials testing new therapeutic agents. Ideally, such biomarkers will either predict susceptibility to retinopathy, neuropathy, or nephropathy; detect early disease; or correlate with pathologic progression. Surrogate endpoints should be reliable, standardized, and easy to use. Investigators responding to this RFA may wish to take advantage of existing epidemiologic or long-term clinical studies that may have been established to investigate diabetes or other diseases. Studies in animal models will be considered responsive to this RFA if these applications have a clear-cut long-term goal of applicability to humans.

Letter of Intent Receipt Date: January 17, 2002
Application Receipt Date: February 14, 2002
To view the full RFA for this program, go to grants.nih.gov/grants/guide/rfa-files/RFA-DK-02-016.html on the Internet.
For more information or clarification on the diabetic nephropathy projects, contact
Barbara Linder, M.D., Ph.D.
Division of Diabetes, Endocrinology, and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 699
MSC 5460
Bethesda, MD 20892–5460
Phone: 301–594–0021
Fax: 301–480–3503
Email: linderb@extra.niddk.nih.gov

In 2000, a National Advisory Council working group recommended that NIDDK lead a nationwide effort to characterize the molecular and cellular features of stem cells during and after development of the pancreas, liver, stomach and intestine, kidney and genitourinary tract, bone, and hematopoietic tissues. This project would find new strategies for repairing or replacing damaged organs and provide new insights into pathologic processes underlying disorders of these organs.

Genome Anatomy Projects (GAPs) have been established by the National Cancer Institute (NCI) and NIDDK to accelerate the discovery of genes expressed in specific tissues, such as tumors or the endocrine pancreas, and to exploit the sequence data emanating from the Human Genome Project. The GAPs foster the development of national networks of laboratories that characterize tissue-specific gene expression and identify novel transcripts. In addition, GAP researchers elucidate patterns of gene expression that produce insight into developmental programs and disease progression and that may eventually be useful in diagnosis and treatment. The bioinformatics systems associated with each GAP ensure that all of the data produced are available to researchers worldwide soon after being generated in the laboratory.

The NIDDK invites cooperative agreement applications to participate in the search for the processes that transform stem cells into tissue-specific cells and organs and the processes by which progenitor cells maintain and regenerate tissues and organs in health and disease. The specific goals will be to develop the necessary biological procedures and reagents for characterizing tissue-specific progenitor cells and to characterize gene expression patterns in these cells using advanced technologies and bioinformatic techniques. The focus of the projects will be on progenitor cells of the gastrointestinal tract, liver, pancreas, kidney, and genitourinary tract in both human and murine systems. Because of the nature of the research questions, the NIDDK is looking for applications that include both investigators with expertise in progenitor cell biology and investigators with substantial expertise in bioinformatics. The GAP components will work together as a consortium.

A major objective of this RFA is to disseminate the data and research reagents generated through each project to the research community as rapidly as possible. Therefore, the application should describe methods for ensuring that the larger research community has access to the data and tools generated by the GAP. In addition, applicants are encouraged to describe opportunities for long- and short-term training of researchers at all levels to take advantage of these data and reagents.

Letter of Intent Receipt Date: February 15, 2002
Application Receipt Date: March 15, 2002
To view the full RFA for this program, go to grants.nih.gov/grants/guide/rfa-files/RFA-DK-02-027.html on the Internet.
For more information or clarification, contact
Rebekah S. Rasooly, Ph.D.
Director, Genomics Program
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 643
MSC 5458
Bethesda, MD 20892–5458
Phone: 301–594–6007
Fax: 301–480–3510
Email: rasoolyr@extra.niddk.nih.gov

The NIDDK seeks applicants to identify and evaluate biomarkers that can be used to predict the development of benign prostatic hyperplasia (BPH) or prostate cancer. Possible biomarkers may also predict a patient's response to two medical treatments for BPH (finasteride and doxazosin) studied in the MTOPS trial, which is about to conclude.

BPH affects more than 50 percent of all men over age 50. Treatment costs an estimated $5 billion a year, and these costs will increase as the U.S. population ages. If left untreated, BPH can lead to urinary tract infections, urinary retention, and, in rare cases, kidney disease. BPH is a heterogeneous disorder, with growth occurring in different portions of the gland. Both clinical presentation and responses to treatment are mixed. Furthermore, although there is no clear link between BPH and prostate cancer, these two diseases occur in a similar population of aging men.

MTOPS acquired prostate biopsies from participants as they entered and exited the trial and maintains these samples in storage. The samples will allow the development and evaluation of potential biomarkers for BPH, prostate cancer, and response to BPH treatment. This initiative will support the creation of a consortium to use this material for cooperative studies to evaluate genetic, immunologic, or biochemical biomarkers relevant to BPH progression, response to therapy, and development of malignancy. MTOPS followup by questionnaire and/or death certificate analysis will be performed.

Letter of Intent Receipt Date: February 20, 2002
Application Receipt Date: March 20, 2002
To view the full RFA for this program, go to grants.nih.gov/grants/guide/rfa-files/RFA-DK-02-017.html on the Internet.
For more information or clarification, contact
Robert Star, M.D.
Extramural Senior Scientific Advisor
National Institute of Diabetes and Digestive and Kidney Diseases
Building 31, Room 9A35
31 Center Drive, MSC 2560
Bethesda, MD 20892–2560
Phone: 301–594–7715
Fax: 301–496–2830
Email: starr@extra.niddk.nih.gov

The purpose of this initiative is to develop, in collaboration with the National Center for Complementary and Alternative Medicine (NCCAM), a multicenter study designed to evaluate and compare alternative medical and approved pharmacologic approaches, alone and in combination, for the effective treatment of BPH. Because these agents are also claimed to have benefits for prostate cancer, input and advice from investigators studying this disease will be sought as well.

Phytotherapy and other alternative medicines are widely used to treat BPH symptoms, although their efficacy has never been studied. The two major phytotherapies, saw palmetto and Pygeum africanum, are widely used in the United States, Europe, and Asia. Many traditional physicians suggest that any benefits are due to the placebo effect, while others assert that the treatment is efficacious even though the mechanism of action is not known. It is essential that these agents be studied and compared with conventional therapy so that physicians can adequately advise patients and treat them with the most effective therapy for their defined symptoms and pathology. A small pilot trial of saw palmetto, cofunded by NCCAM, is under way.

For more information or clarification, contact
Leroy M. Nyberg, Jr., Ph.D., M.D.
Director, Urology Program
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 627
MSC 5458
Bethesda, MD 20892–5458
Phone: 301–594–7717
Fax: 301–480–3510
Email: nybergl@ep.niddk.nih.gov

African Americans disproportionately experience ESRD in that they constitute approximately 12 percent of the U.S. population but 32 percent of the ESRD population. Diabetes mellitus is the predominant cause of ESRD in the U.S. population, but in African Americans especially, hypertension is a major cause of ESRD. In 1990, the NIDDK launched an initiative to investigate the underlying cause of hypertensive kidney disease and to study mechanisms that could slow its progression in African Americans. The AASK was initiated to investigate whether a specific class of antihypertensive agents and/or the level of blood pressure would influence the progression of hypertensive kidney disease in African Americans.

After a brief pilot study (1992–1994), 20 clinical centers and a data coordinating center were funded in 1994 to carry out the full-scale clinical trial. The 21st clinical center was added in June 1996. As in the pilot clinical trial, all four historically black medical schools are participating in the full-scale trial. The centers needed 9 months to revise the protocol for the full-scale trial, and participant recruitment and randomization began in April 1995. The intervention component is scheduled to end in March 2002, and the primary analysis of the study results will conclude in June 2002. A cohort study will commence at the conclusion of the intervention study. The investigators at the clinical and data coordinating centers and the program staff at the NIDDK planned the format of the "After-AASK" Cohort Study in 2001.

The AASK cohort will continue to be followed at the clinical centers, except for some patients at centers with a small number of participants, who will be followed at nearby larger centers. In some instances, the smaller centers may be asked to recruit additional African Americans with hypertensive kidney disease to augment their patient population. Patients will be provided with the same clinical care given at the respective centers. Baseline demographic information, selected laboratory tests, and other studies will be obtained when the cohort study begins. Patients will be seen four times a year at the centers, and some selected studies will be done at these visits. Samples will be obtained and stored for later studies and analyses. To permit ultimate integration and comparison of the two data sets, the protocol used in the AASK Cohort Study will be similar to that proposed for the new Chronic Renal Insufficiency Cohort Study (CRICS) to be initiated by mid- to late 2002.

For more information or clarification, contact
Lawrence Agodoa, M.D.
Director, Office of Minority Health Research Coordination
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 653
MSC 5458
Bethesda, MD 20892–5458
Phone: 301–594–9652
Fax: 301–594–9358
Email: agodoal@ep.niddk.nih.gov

The NIDDK invites investigators to apply for a grant to develop educational programs to increase organs and tissue donated for transplantation by racial and ethnic minorities and other underserved populations.

This RFA is intended to stimulate investigators to develop educational programs to improve the understanding of the benefits of organ and tissue transplantation and the need, especially in racial and ethnic minorities and other underserved populations, to donate organs and tissues. The grant will provide support for the development of educational programs in the relevant communities to promote health, enhance understanding of organ and tissue donation, and initiate programs that will increase participation.

This RFA is based on recommendations by investigators and community leaders, and on comments on the NIDDK strategic plan to reduce and eliminate health disparities in racial and ethnic minority communities. The National Advisory Council subsequently approved the concept.

Racial and ethnic minorities, particularly African Americans, American Indians, Alaska Natives, and Hispanic Americans, disproportionately experience ESRD. Although transplantation is the preferred therapy because survival and quality of life improve for successful transplant recipients, these minority groups receive transplants less frequently. An often-cited reason for the lower transplantation rate is that the organ donation rate in these minority groups is much lower than their representation in the ESRD patient population. Increased numbers of minority organs in the pool would mean a better match and, ultimately, better graft survival.

Over the past 5 to 8 years, several programs have been initiated to increase minority organ and tissue donation. The Minority Organ and Tissue Transplant Education Program, funded by the National Center for Minority Health and Health Disparities and NIDDK, was established, and intensive educational and information activities have occurred in 15 U.S. cities. During the same period, the Department of Health and Human Services intensified educational and information programs throughout the country through the Organ and Tissue Donation initiative. Perhaps as the result of these combined efforts, organ and tissue donation has increased, especially in minority communities, although the donation rate from minorities is still lower than their representation in the population with organ failure, especially ESRD. Increasing the educational activities in racial and ethnic minority communities, as well as in underserved populations, will enhance the proportion of their organs in the pool and hence increase the chances of a better match and improved graft survival.

The program is intended to create an environment supportive of organ donation by

• increasing exposure to donation messages and opportunities to express a commitment to donate
  
  
• evaluating the impact of increased support for living organ donation
  
  
• increasing minority cadaveric and living organ donation
  
  
• increasing donation from nontraditional donors (older donors, living donors, etc.)
  
  

Applications were received in December and are being evaluated for scientific and technical merit by an appropriate peer review group convened by the NIDDK. Generally, the top half of the applications under review are discussed, assigned a priority score, and receive a second-level review by the National Advisory Council.

To view the full RFA for this program, go to grants.nih.gov/grants/guide/rfa-files/RFA-DK-02-019.html on the Internet.
For more information or clarification, contact
Lawrence Agodoa, M.D.
Director, Office of Minority Health Research Coordination
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 653
MSC 5458
Bethesda, MD 20892–5458
Phone: 301–594–9652
Fax: 301–594–9358
Email: agodoal@ep.niddk.nih.gov

New Programs

Over the past year, a strong interest has developed throughout the renal community in the potential of intensified dialysis regimens, either slow nocturnal or short daily dialysis, to improve patient outcomes. As a strategy to improve dialysis dose, increasing frequency has a number of theoretical advantages, since clearance of accumulated toxins is greatest early in a dialysis run. At a small number of sites with carefully selected patient groups, markedly improved patient rehabilitation, better control of plasma phosphate, and reduced erythropoietin requirements have been reported with more frequent dialysis.

In collaboration with the Centers for Medicare & Medicaid Services (formerly the Health Care Financing Administration), the NIDDK organized an intensive 2-day planning meeting of dialysis experts to explore the feasibility of a randomized trial or observational studies of these new treatment strategies. Experts at the meeting expressed interest in learning more about these new approaches, discussed the feasibility of a trial, and recommended a rigorous evaluation using randomized participants.

The NIDDK is requesting applications to support the implementation of a carefully designed randomized trial of frequent dialysis. The overall goal is to assess the impact of more frequent dialysis on patient morbidity and mortality. A planning group will be established in 2002, with the expectation that the trial will be fully implemented by 2003.

For more information or clarification, contact
Paul Eggers, Ph.D.
Director, Kidney and Urology Epidemiology Program
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 615
MSC 5458
Bethesda, MD 20892–5458
Phone: 301–594–8305
Fax: 301–480–3510
Email: eggersp@extra.niddk.nih.gov

The benefits of therapeutic interventions in clinical practice are often enhanced by placebo effects, defined as the positive physiological or psychological changes associated with the use of inert medications, sham procedures, or therapeutic symbols within a health care setting.

Placebo effects may also be viewed as a subset of a larger group of mind-brain-body effects that influence the prevalence and severity of specific diseases. An increasing body of research has documented the psycho/physiological effects of cultural and socioeconomic systems, religious beliefs and devotional practices, meditation, faith-based healing, and hypnosis.

The NCCAM has issued an RFA to stimulate investigator-initiated research on how placebos and placebo effects affect clinical practice. Several NIH Institutes and Centers, including NIDDK, have joined NCCAM to support this initiative. Another solicitation from NIDDK will call for applications to address these issues in relation to clinical trials.

Understanding how to enhance the therapeutic benefits of the placebo effect in clinical practice may significantly improve health care. The objectives of this initiative are to encourage interdisciplinary studies involving social and behavioral sciences, as well as other appropriate scientific disciplines, to reveal those factors important for eliciting placebo effects in clinical practice. An important goal is to understand what factors are necessary to elicit a placebo effect so that the benefits of a particular therapeutic intervention can be enhanced to improve health and promote wellness.

Letter of Intent Receipt Date: March 1, 2002
Application Receipt Date: April 11, 2002
To view the full RFA for this program, go to grants.nih.gov/grants/guide/rfa-files/RFA-AT-02-001.html on the Internet.
Researchers interested in studying the placebo effect as it applies to treatments for diabetes and digestive and kidney diseases should contact
Leroy M. Nyberg, Jr., Ph.D., M.D.
Director, Urology Program
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 627
MSC 5458
Bethesda, MD 20892–5458
Phone: 301–594–7717
Fax: 301–480–3510
Email: nybergl@ep.niddk.nih.gov

KUH/NIDDK, the Biology of Aging Program of the National Institute on Aging (NIA), and the Cancer Cell Biology Branch of the NCI invite applications through the exploratory/developmental (R21) grant mechanism from investigators with kidney-related research interests that fall within the purview of the mission of the National Institutes of Health (NIH). Program planners hope to foster the development of exploratory pilot and feasibility research by newly independent or established investigators. The program will enable investigators to develop new ideas enough to allow for subsequent submission of R01 applications focusing on research problems relevant to the study of acute and chronic kidney diseases and their complications in both adults and children. These grants are not intended to support or supplement the ongoing funded research of an established investigator or to serve as an alternative mechanism of support for projects not receiving funding as competitive continuation applications.

Appropriate topics for investigation would include, but are not limited to,

• development of methods to identify and define novel signaling molecules and pathways involved in renal cellular and tissue development, and the genetic programming of renal morphogenesis and angiogenesis.
  
  
• development of animal models that reflect the complexity of human kidney diseases and permit exploration of candidate mechanisms leading to development, injury, or tolerance to injury.
  
  
• development of less complex models to take advantage of evolutionary-conserved mechanisms involving responses to injury and repair.
  
  
• development of new approaches for using mutant organisms to study membrane transport.
  
  
• development of technological tools to improve molecular studies of renal disease, such as methods to permit parallel assessment of gene expression on renal biopsies.
  
  
• development of novel vectors and delivery systems for use in gene therapy of systemic and inherited kidney diseases, including polycystic kidney disease and diabetic nephropathy.
  
  
• development of new methods to determine the role of complement and complement regulatory proteins, oxidants and proteases, cytokines, chemokines, growth factors, and adhesion molecules and matrix components in immunologic kidney disease.
  
  
• combinatory chemistry for the development of new renal reagents.
  
  
• identification and characterization of early markers of renal disease severity.
  
  
• identification of novel approaches to improve immediate and long-term outcomes in pediatric chronic renal failure.
  
  
• development of new methods for temporal and spatial control of transgene expression in the kidney.
  
  
• development of micromethods and miniaturized assays for physiologic and metabolic studies/measurements in small/young animals and children.
  
  
• development and use of array technology and bioinformatics to characterize renal tissues in health and disease states.
  
  
• use of molecular and proteomic techniques, such as differential displays, arrays, second-generation library screens, two-dimensional gels, and so on, to screen for novel kidney tissue-specific genes, novel disease or regulatory genes, or etiologic agents.
  
  
• use of phage display or other novel approaches to identify kidney-specific proteins.
  
  
• development of novel strategies for treating progressive renal disease using animal models and/or short-term feasibility studies in humans.
  
  
• identification of new factors contributing to symptoms and morbidity in patients with treated ESRD.
  
  
• use of molecular and proteomic techniques on urine, blood, or tissue to discover more sensitive markers of chronic renal disease, its progression, and its response to treatment.
  
  
• identification of new pathophysiologic mechanisms and modes of treatment for diabetic nephropathy.
  
  
• use of epidemiologic and biochemical approaches to identifying new, nontraditional risk factors for cardiovascular disease in patients with chronic renal disease.
  
  
• studies focused on age-related changes in the biology of the kidney and kidney function, and propensity for diseases of the kidney relevant to older subjects.
  
  
• studies focused on mechanisms of biological, chemical, and physical carcinogenesis and subsequent tumor growth and progression to kidney metastasis.
  
  

Inquiries from potential applicants are encouraged. Relevant Scientific Program Officers may be identified through the KUH web page at www.niddk.nih.gov/welcome/org/tables/kuh_table.htm or by making direct inquiries to
M. James Scherbenske, Ph.D.
Director, Renal Physiology/Cell Biology, Kidney Centers, and Small Business Innovation Research Programs
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 613
MSC 5458
Bethesda, MD 20892–5458
Phone: 301–594–7719
Fax: 301–480–3510
Email: scherbensk@ep.niddk.nih.gov

KUH/NIDDK and the Division of Cancer Biology at the NCI invite exploratory/developmental (R21) grant applications from investigators with research interests that focus on urology and serve the mission of the NIH. Program planners hope to foster the development of exploratory pilot and feasibility research by newly independent or established investigators working on a new line of research. Information thus obtained would allow subsequent submission of R01 applications focusing on research problems relevant to the study of urologic diseases and their complications. These grants are not intended to support or supplement the ongoing funded research of an established investigator or to serve as an alternative mechanism of support for projects not receiving funding as competitive continuation applications.

Areas in which such scientific opportunities exist include, but are not limited to,

• identification of novel signaling molecules and pathways involved in urologic cellular and tissue development, differentiation, transcription, and function.
  
  
• identification and characterization of cells capable of repopulating urologic organs (stem cells).
  
  
• development and characterization of promoters to drive gene expression in urologic tissues.
  
  
• development, characterization, and utilization of novel cellular and animal models of urologic diseases.
  
  
• development of novel vectors and delivery systems for use in gene therapy of urologic diseases, including both inherited disorders, such as hereditary oxalosis, and disorders thought to be acquired, such as prostatitis, interstitial cystitis, and urologic complications of diabetes.
  
  
• development of new methods for temporal and spatial control of transgene expression in urologic tissues.
  
  
• identification and characterization of biologic markers for the development or progression of urologic diseases.
  
  
• development and characterization of full-length genetic libraries from understudied urologic tissues, especially the urinary bladder.
  
  
• use of molecular biologic and proteomic techniques to screen for novel urologic tissue-specific genes, novel disease or regulatory genes, or etiologic agents.
  
  
• development and use of array technology and bioinformatics to characterize profiles of gene expression in healthy and diseased urologic tissues.
  
  
• use of phage display or other novel approaches to identify cellular receptors in urologic tissues.
  
  

Inquiries from potential applicants are encouraged. Relevant Scientific Program Officers may be identified through the KUH web page at www.niddk.nih.gov/welcome/org/tables/kuh_table.htm or by making direct inquiries to
Leroy M. Nyberg, Jr., Ph.D., M.D.
Director, Urology Program
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 627
MSC 5458
Bethesda, MD 20892–5458
Phone: 301–594–7717
Fax: 301–480–3510
Email: nybergl@ep.niddk.nih.gov

The NIH is offering a Medical Student Loan Repayment Program designed to recruit and retain health professionals who are actively pursuing research. Medical students in clinical and pediatric research are especially encouraged to apply.

For more information about training and career development opportunities at NIH, contact
Terry Bishop, Ph.D.
Director, Training and Careers Program
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 619
MSC 5458
Bethesda, MD 20892–5458
Phone: 301–594–7721
Fax: 301–480–3510
Email: bishopt@extra.niddk.nih.gov

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