Training Candidates

Recruitment Process

Applications are received in response to notices at national scientific meetings and on-line on the divisional web site, the web sites of the American Society of Nephrology, and the National Kidney Foundation. Many are based on the programs’ national and international reputations. Beginning this year, the program will be accepting application only through the American Association of Medical Colleges Electronic Residency Application Service (ERAS).  ERAS is an internet based application process developed by the AAMC to transmit and streamline fellowship applications to different institution.

Qualification Criteria

Applicants must be US citizens or permanent residents.  Physician candidates have completed all training in the US for qualification in the American Board of Internal Medicine.  They must express an interest in becoming a physician-scientist in academic nephrology.  Prior research experience or other evidence of commitment to research, is highly desirable.  This proposal includes a request to expand the program with limited number of qualified individuals with a PhD (or an equivalent degree) and a career goal in academic nephrology.

Selection of Candidates

The candidates are screened by the Director and Co-Directors.  They are ranked based on their academic qualifications, research experience, and career potential.  Following a meeting of the core and clinical faculty in the division of Nephrology and Hypertension, candidates are invited for interviews with the program faculty.  Candidate are appraised by a standard evaluation form, ranked and top candidates invited for interviews.  This process of Nephrology fellow selection is being centralized by the ACGME during the year.

Quality and Depth of Applicant Pool

There has been a steady growth of about 40% over the last five years in the number of applications received (Table V).  The quality of the applicants has increased substantially.  Whereas in the first two years (when the fellows were not offered NIH-funded research training at their interviews because this grant was not awarded) all applicants offered a position entered the program, subsequently, only half of those offered entered the program.  We now compete with the best programs nationally for a limited number of top candidates who have expressed interest in entering academic nephrology.  The availability of research funding through this grant, is just beginning to show in the sharp increase in quality of candidates (see figure 4) who are strong prospects to enter academic careers in nephrology.

MINORITY RECRUITMENT AND RETENTION PLAN

History

The Department of Nephrology and Hypertension established a reputation for training fellows from the top programs internationally under the prior Division Chief, George E. Schreiner, MD.  We aggressively recruit individuals from underrepresented racial/ethnic groups.  Kathryn Sandberg, PhD is a leader in the program to promote women in science.  She champions the training of women in her laboratory and at GU.  Our faculty seeks to recruit minority and female applicants from the house staff of GU.  Fellowships are advertised in Academic Physician and Scientist which is distributed to all residents and fellows in the US and to the 2000 recent alumni of US minority medical schools.

Achievements

Our program has been quite successful in recruitment and retention of minority trainees.  Of the 13 fellows recruited into this program, 4 are female (Mere, Borrego-Conde, Raggio, Nouri), one is African American (Mere), one is Hispanic (Borrego-Conde), one is Indian - American (Patel), and 5 are Asian American (Luo, Nouri, Li, Chen, Zhou).  70% of our fellows are either female and/or from an underrepresented racial/ethnic groups.  Our first two graduates, Drs. Mere and Borrego-Conde are both female from underrepresented groups and both have secured fulltime academic appointments in minority institutions.  Dr. Mere is an Assistant Professor of Nephrology at Howard University in Washington, DC, and Dr. Borrego-Conde is an Assistant Professor of Nephrology at the University of Puerto Rico.  A subsequent Asian-American trainee, Dr. Patel, has a part-time appointment as an Assistant Professor at GU.

D.1.  Required courses

The Department of Medical Ethics is chaired by Edward Pelligrino, MD, who is an acknowledged leader in the field.  The Ethics in Science Course at GU includes sessions devoted to ethical dimensions of human and animal research; ethical dimensions of study conduct; data collection analysis; reporting research including data selection, obligations of authorship; plagiarism; obligations of editors and reviewers; research funding and ethical considerations of public versus private sector support, attribution and conflict of interest; and ethical relationships with colleagues including how to face suspicions or knowledge of unethical conduct.  Several sessions of the NIH Principals and Practice of Clinical Research Course are devoted to key issues in the responsible and ethical conduct of research.  There are 2 hours devoted to ethical problems in clinical research; 2 hours to legal issues in clinical research; 2 hours to scientific conduct; 2 hours in mock IRB meetings; and 2 hours in ethics case studies.  Both of these courses are required for research fellows.

D.2.  Other instruction in responsible conduct of research

Each fellow involved in animal research is instructed in responsible care of animals, handling and protection.  Dr. Welch is the chair of the GU Animal Use and Care Committee.  He mentors trainees in how to prepare an application to use animals and how to calculate the minimum number of animals needed for each protocol.  Each fellow involved in clinical research is instructed in ethics and subjects’ rights in clinical research, biological and radiation safety, and grants and authorships by the research mentor and other members of the core faculty.  Clinical trainees are encouraged to select a 3-month rotation as a non-voting member of the IRB. 

PROGRESS REPORT

E.1.  Postdoctoral training, history, and accomplishments

We have only 4 years of experience of this funded research training program.  Significant areas of success include the 40% increased number (Table VI) and strength of the candidates reflects in our current ability attract those with substantial prior research training and publication (figure 4), the high proportion (70%) of female and minority candidates, the strong publication record of the candidates with thirteen manuscripts published or in press, most in high impact journals (JCI, JASN, KI, AJP, Hypertension), 8 manuscripts under review and 5 in preparation, 28 abstracts and 13 reviews or chapters (Table VII), and the placement of the two graduate trainees in full-time faculty positions in divisions of nephrology in minority institutions, and three in part-time academic positions in nephrology divisions, leave one in full time clinical practice (Table VI).  Nevertheless, we are not satisfied that only two of the graduates are in full-time academic nephrology.  We recognize in retrospect that those who chose part-time academics or full-time private practice are trained at their own expense in medical schools in the USA, and accumulated large debts that have to be repaid, thereby putting extreme financial pressure on them to seek positions in private practice.  Each would have been competitive for a career in academic nephrology.  Of the five fellows entering in year 04/05, all received their primary training overseas and have no debt to repay.  We anticipate that this will free them to follow careers of their choosing.  This is a motivation for our request for additional funds to train basic scientists in nephrology at the post-doctoral level, since they will not have the financial incentive to seek positions outside of academia.

Current Trainees (Training dates)

Julie Raggio, MD (2003-present).  She obtained her BA at Dartmouth College, NH in 1989 and her MD at the University of Texas Southwestern Medical School in Dallas in 1998 and her internship and residency at the University of New Mexico in Albuquerque. During her internship and residency, she undertook 2 clinical projects: one was on BP control in patients with renal insufficiency and another on thyroid disease in renal failure patients.  Since she was committed to academic nephrology, had some research experience, and was very well-trained, we accepted her into our program.  After one year of clinical training, she is presently completing her second year of research training under this grant.  Her training was interrupted by three months of maternity leave.  Consequently, she will continue training for three months into the present academic years to complete 24 months of training under this grant.  She joined the laboratory of Dr. Wilcox and works closely with Drs Wang (expert in ex vivo microprofusion of rodent and human microvessels), Dr. Chabrashvili and Gill (experts in molecular biology).  She is completing a project on the roles of dimethylarginine dimethylaminohydrase (DDAH-1 and -2) in the regulation of plasma levels of asymmetric dimethylarginine (ADMA) and endothelium dependent relaxing factor/nitric oxide (EDRF/NO) response of rat microvessels.  For this demanding and original study, she first learned techniques of rat handling, mesenteric microvessel dissection, mounting and study in a Mulvany–Halperin four vessel myograph and became skilled in endothelium-dependent relaxation.  She characterized two responses in rat mesenteric resistance vessels, EDRF, and EDHF.  Next, she developed and validated small interference RNAs (siRNA) against DDAH -1 and -2 or control sequences which she injected in conscious rats.  She sampled blood and mesenteric vessels and isolated endothelial cells to quantify endothelial mRNA.  She discovered that EDRF/NO responses are abolished following silencing of DDAH-2 that was confirmed by reduction in the specific mRNA and protein expression in the resistant vessels and endothelial cells.  The results have been presented in abstract form and are being prepared for publication.  She will graduate this October.  She has 2 peer-reviewed manuscripts in preparation, 2 chapters and reviews and 5 abstracts published during her training to date (Table VII A). She is interviewing for positions in academic nephrology divisions where she can combine research with clinical practice and teaching.

Adam Pearlman, MD  (2004-present)  He graduated magna cum laude from Tufts University in 1995 and MD from Emory University in 1999 where he completed his internship and residency and an additional year as Chief Medical Resident.  Prior to joining our program, he published papers in the Journal of Immunology and in the Journal of Clinical Anesthesiology. We considered him an exceptional and well-trained physician with research experience in successful academic programs. He completed 1 year of clinical nephrology and, in July 2004, began 2 years of research training under this grant.  He elected to work on a new technique of pressurized and perfused rat and mouse mesenteric resistance vessels that allows control of pressure and flow to study vascular reactivity and autoregulation on a daily basis with Dr. Chen (expert in microvascular physiology and free radical mechanisms).  He is studying the roles of SOD and H₂O₂ in vascular responses.  He has discovered that the acute microvascular relaxation with Cu/Zn-superoxide dismutase (SOD) or nitroxide SOD mimetics, such as tempol, depend on the generation of H₂O₂, rather than the reduction of superoxide anion, since they are prevented by catalase.  He has found that H₂O₂ exerts a biphasic response: an initial vascular contraction at low H₂O₂ concentrations that depends on thromboxane-prostanoid [TP] receptors is followed by a sustained and powerful vasodilatation that depends on potassium channels in VSMCs.  He is applying a novel H₂O₂-sensitive microelectrode developed by Dr. Chen to assay directly the generation of H₂O₂ within the lumen of these microvessels_.  His preliminary studies are accepted for presentation at the American Society of Nephrology meeting.  He has one abstract and one review published (Table VII A). During this year, he will extend these to human microvessels.

Zaiming Luo, MD, MS (2005-present).  He was educated in Shanghai, China where he graduated with an MD and a PhD from the Second Medical University of the People’s Republic of China.  He was trained as a resident and completed cardiology fellowship before joining the Indiana School of Medicine as a visiting scholar for 2 years in 1993.  After 2 further years as an attending physician in Cardiology at his university in China, he joined Susan Bagby’s laboratory of molecular pathology at the University of Oregon Health Science Center in Portland for 5 years in 1998.  In 2003, he was recruited by Gary Owens, PhD as a postdoctoral research associate in the Department of Molecular Physiology at the University of Virginia.  He is entering a period of research training supported by this grant this year.  He has authored 19 papers in peer review journals, including JBC, JASN, AJP, etc.  We considered ourselves fortunate to recruit such an exceptional and well-trained physician-scientist to our research program.  With Dr. Owens, he developed novel methods to study epigenic regulation of VSMCs based on histone methylation and acetylation.  He proposes to apply these skills to the problems of angiotensin-induced changes in renal microvascular gene expression and reactivity in oxidative stress.  In only four months he has developed a new whole-cell assay for O₂^.- using chemiluminescence in a 96-well plate, and has established promoter-reporter assays for p67^phox, p47^phox and p40^phox in transiently transfected isolated preglomerular VSMCs.  He will use these to test his hypothesis that oxidative stress involves upregulation of the SRF (transcription factor) marker gene expression through increased SRF binding and histone modification in preglomerular VSMCs.  He is co-mentored by Drs Jose and Wilcox.  He has 2 peer reviewed manuscripts published, and 4 under review and 2 abstracts published to date (Table VII A). It is his plan to seek a faculty position in nephrology on completion of this training.

Pouneh Nouri, MD (2005-present).   She received her schooling in Tehran, Iran and undertook 8 years at the Iran University of Medical Sciences and Health Services in Tehran where she obtained her medical diploma and clinical internships and residency.  In 2000, she took one year of research training at Stanford University Division of Nephrology in Paolo Alto, California studying the post-growth hormone receptor signaling defects in CRI with Ralph Rabkin followed by a research assistantship at Columbia University in New York where she studied molecular biology.  Prior to joining our program, she co-authored a manuscript in the Journal of Clinical Investigation.  We considered her a strong candidate because of her independence, her ability to seek out successful research initiatives in the U.S., and her strong recommendations.  She undertook internship and resident training at San Lukes Roosevelt Hospital in New York and entered our program as a nephrology fellow in 2004.  This year she starts two years of research fellowship supported by this grant.  She is in her first month in the laboratory where she is learning basic techniques.  She has elected to undertake a study of vascular remodeling in human subcutaneous resistance vessels with Drs Wilcox and Wellstein.  She has one peer reviewed manuscript published to date (Table VII A).  She has expressed a strong interest in becoming an academic nephrologists on completion.

Trainees that completed the program during the past five years (training dates).

Lillian Borrego-Conde (2001-03). She received her schooling in San Juan, Puerto Rico and, a summer research student at Cornell University and at the University of Sacred Heart in Puerto Rico and obtained her BA at Georgetown University in 1993 and her MD at the University of Puerto Rico in 1997.  She completed her internship and residency and became Medical Chief Resident at the University of Puerto Rico School of Medicine.   During her residency, she undertook 2 research projects: one on renal osteodystrophy and another on hemodialysis patients in Puerto Rico. We considered her a strong candidate for research training since she was highly motivated and committed to returning to Puerto Rico as an academic nephrologist.  She entered our fellowship training program in 2002, and after one year of clinical training, completed two years of research under this grant.  She worked closely with Dr. Wang to develop myographic methods to study reactivity of mesenteric resistance vessels from the rabbit.  Her primary project was the role of oxidative stress and TP receptors in abnormal contraction and relaxation mechanisms in isolated resisted arteries from angiotensin-infused rabbits.  She established rabbit and mouse models of the angiotensin slow pressor response and discovered that renal afferent arterioles from Ang II-infused rabbits have enhanced mRNA expression for p22^phox and COX-2.  Therefore, she studied their roles in the enhanced contractility of the vessels.  During her research, she completed three studies.  She has 3 peer reviewed manuscripts, 6 abstracts and one review published (Table VII B).  They were published in Kidney International, the Journal of the American Society of Nephrology and the Journal of Vascular Research.  She obtained a full-time faculty position in the division of nephrology at the University of Puerto Rico where she is presently an assistant professor engaged in research, clinical care, and teaching.  She directs their nephrology fellowship training program.

Kinjal Patel, MD (2001-03).    He graduated cum laude with honors and Dean’s list in Science and Biology from Georgetown University in 1993 and MD in 1998 from Georgetown University where he completed his residency.  We considered him a strong candidate because of his excellent training, intelligence, and motivation.  He completed two years of research under this grant program followed by one year of clinical training.  His interests centered on new mechanisms for treatment of oxidative stress in hypertension.  He completed two projects.  The first study was on the mechanism of acute antihypertensive actions of nitroxides in the SHR.  He learned the techniques for study of BP and renal function and undertook a structure-activity relationship within a family of nitroxides.  With Dr. Chen, he characterized the SOD mimetic activity and lipophilicity of these compounds.  Thereafter, with Drs Welch and Wilcox, he undertook dose-response studies for the acute antihypertensive action of these agents.  He discovered that the acute antihypertensive and bradycardic response to nitroxides are closely dependent on their SOD mimetic activity whereas the sensitivity is invariably related to lipophilicity.  This work is completed and has been accepted for publication in the American Journal of Physiology.  For his second project, he investigated the roles of angiotensin and COX-derived thromboxane using agents that block oxidative stress, AT₁ or TP receptors or COX-1 or -2, in a rat model of renovascular hypertension.  He found that blockade of oxidative stress, AT₁ or TP receptors were effective in reducing blood pressure, but that they had quite different effects on renal hemodynamics and parameters of oxygenation.  These original findings are under review in Hypertension.  He has 3 peer reviewed manuscripts, 3 abstracts and one chapter published (Table VII B).  He joined the leading group of clinical nephrologists in the DC area, and has a part-time position in our division of nephrology and hypertension where undertakes teaching and research.

Constance Mere, MD  (2001-02). She obtained her MD from the University of Nigeria in 1992, followed by internship and residency, and an appointment as the medical officer of her hospital.  In 1997, she undertook 2 years of research training at Harlem Hospital, NY undertaking clinical research followed by 3 years at the University of Connecticut Health Center as a resident in Internal Medicine.  She was selected as a well-recommended and mature physician with some research experience who was a successful and potential academic member as an African American female.  After 1 year of clinical nephrology training, she undertook one year of research under this grant followed by a second year of research sponsored by Divisional funds.  Her research interest was in clinical nephrology where she worked with Dr. Llach on three clinical protocols for treatment of hyperphosphatemia and bone disease in patients with end stage renal disease.  Her projects were on divalent ions and vitamin D abnormalities in chronic kidney disease; a double blind, randomized study of the control of hyperphosphatemia with a novel phosphorus binder (a polyamine) in patients with ESRD and a double blind, randomized study of the therapeutic use of oral paricalcitrol in patients treated with hemodialysis or CAPD.  She helped to develop the protocol, set up the studies and recruited the patients.  The first study is complete and is presented for publication.  The latter two are large, multi-centre studies for which Dr. Llach is the PI.  They are now complete, the code is broken and Dr. Mere is helping to analyze the data with Dr. Llach.  Dr. Llach anticipates that she will be first or second author on these studies.  She has one peer reviewed manuscript under review, and two reviews published (Table VII B).  Dr. Mere obtained a position as a full-time assistant professor of medicine in the division of Nephrology at Howard University, Washington DC, where she directs their nephrology fellowship training program.

Paul Modlinger (2002-04).  After graduating magnum cum laude and Dean’s list from the University of Pennsylvania in 1993, he entered New York University School of Medicine where he received honors and an MD in 1997. He completed a residency in Internal Medicine at University of Pennsylvania before joining our program as a fellow in nephrology in July 2001.  He was authored a full paper in the Journal of Virology in 1995.  He was selected as an exceptionally well-trained and motivated physician with background and abilities for a career in research.  The first year of his nephrology training was devoted to clinical training.  He completed two years of research training under this grant in July 2002.    He first learnt how to study mouse models of hypertension.  He made rapid progress and contributed to a study of TP receptors and oxidative stress in the angiotension slow pressor response that was published in the American Journal of Physiolgy.  A study of BP regulation in COX-1 deficient mice was published in Hypertension and a study of 2K, 1C hypertension is under review at Hypertension.  However, his main focus was an ambitious project to study the role of p22^phox in angiotensin-induced oxidative stress and hypertension.  He was the first to develop in vivo small interference RNAs (siRNAs) to investigate a physiologic pathway.  These studies are complete and have been reviewed by Circulation Research who requested some additional studies and the paper is under re-review.  He is the first author on the manuscript.  He has graduated from the program and joined the premier nephrology practice in Northern Virginia.  He has a part-time appointment as an Assistant Professor of medicine in our division of nephrology and hypertension where he participates in teaching and clinical research projects.  He has 2 peer reviewed manuscripts published, two under review and one in preparation, 8 abstracts and 4 reviews or chapters published (Table VII B).

Aaron Kulick (2003-05).  He received his BA from Amherst College, MA and his MD and medical training at Temple University in Philadelphia.  After completing a year of clinical nephrology training, he undertook two years of research supported by this grant.  He elected to learn renal micropuncture and microperfusion with Dr. Welch.  His project was on the role of adenosine type 1 receptors in adapting proximal tubular sodium reabsorption to changes on salt intake in the rat.  He learned how to study proximal reabsorption of fluid and sodium, and used a novel selective adenosine Type I receptor antagonist to construct dose-response relationships for inhibition of proximal reabsorption in rats adapted to low, normal and high salt intakes.  He related these findings to studies that he made of adenosine A1 receptor expression in isolated microdissected tubule segments.  He demonstrated salt-induced inhibition of proximal reabsorption that was related to salt-induced reduction in A1 receptors in the proximal tubule that he showed mediated the changes in reabsorption of salt and water.  These findings were presented by him to the American Society of Nephrology and the American Society of Physiology meetings and are in press for publication in the Journal of the American Society of Nephrology for which he is the first author.  He also has one reviews and one abstract (Table VII B). He has accepted a position as a clinical nephrologist in a private practice and a junior faculty position at the University of Pittsburgh, Division of Nephrology.

Oscar Adler, MD (2003-05).  He obtained his MD and residency training from Kazan Medical Institute in Russia in 1984 and completed a PhD from Kazan in 1987 where he was appointed Assistant Professor in Internal Medicine.  In 1999, he undertook a 3 year residency at Temple University in Pittsburgh before entering our program in 2002.  He published 13 papers between 1980 and 2002 of which he was first or senior author on 9. He came to the research experience with significant prior experience as an investigator backed by solid publications.  This experience and his PhD training indicated that he had the right background to benefit from research training in Nephrology. After completing one year of full-time nephrology training, he completed two years of research supported by this grant.    His interest was in mechanisms of hypertension and vascular and renal dysfunction in models of progressive kidney disease.  In studies with Drs. Welch and Wilcox, he first developed a rat model of reduced renal mass based on one and two thirds nephrectomy.  He selected the technically more demanding surgical reduction of renal mass since it is not confounded by increases hypertension.  He found an increase in the plasma concentration of asymmetric dimethylarginine (ADMA) and therefore focused on dimethylarginine dimethylaminohydrolase (DDAH) in these models.  His first project was on the roles of oxidative stress, NADPH oxidase and AT₁ receptors in DDAH activity in a rat model of reduced renal mass.” He developed a new method to study directly DDAH activity in tissue extracts based on conversion of [¹⁴C] ADMA, to [¹⁴C] citrulline using a custom-synthesized labeled ADMA.  He undertook extensive characterization of this reaction and demonstration inhibition of DDAH activity by citrulline, ADMA and arginine.  He perfected the assay which he applied to rat tissues in the renal failure model.  The experiments are being completed and will be prepared for publication with Dr. Adler as first author.  The second project was to evaluate DDAH activity in different organs of the rat.  This also is complete and will be prepared with Dr. Adler and Dr. Raggio as first authors.  He has recently graduated and accepted a position as a clinical nephrologist in Maryland.  He has one manuscript published and two in preparations, 2 abstracts and one chapter published (Table VII B)

Trainees that will enter the program next year

Haobo Zhou, MD, PhD.  He completed his MD from Shanghai Medical University, China in 1990, his PhD in Molecular Biology at Tuft’s University School of Medicine in 1999 with a research merit scholarship, his postdoctoral fellowship in the Department of Molecular Microbiology at Tuft’s University, and his residency training at Roger William Medical Center in Providence, Rhode Island before joining our program on July 1, 2005.  He has published 4 papers.  We consider him a very strong candidate because of his training at an excellent Chinese university, and PhD training at Tuft’s University.  We anticipate that he will undertake 2 years of research training under this grant starting in July 2006 when his clinical training is complete.

Xueguang Chen, MD, PhD.  He obtained his MD at Anhu Medical University, Hefaei in China in 1986 and, completed an MSc in Clinical Pharmacology in 1987 and a PhD in Pharmacology at Northeastern University in Boston in 1999 where he studied potassium channels using patch clamp techniques.  He devoted one year as a postdoctoral research fellow at the Brigham Women’s Hospital to work on endothelin followed by one year as a postdoctoral research fellow at Northeastern before undertaking internship and residency at Albert Einstein College of Medicine in New York.  He has published 12 articles in peer review journals including PNAS and Journal of Neuroscience of which he is first or senior author on 4.  We considered him an excellent candidate for research training because of his commitment and PhD in Pharmacology. Presently, he is undertaking 1 year of clinical nephrology training but we anticipate that in July 2006 he will undertake 2 years of research training under this grant, starting July 2006.

Ping Li, MD.  He received his MD from the China Medical University in China in 1990, his internship and residency at the top rated Beijing Medical University in China before joining the Department of Physiology and Pharmacology at Bowman Gray School of Medicine in Wake Forest as a postdoctoral fellow for 2 years in 1992, where, in 1994, he was appointed a research associate and, in 1997, as an instructor.  In 1998, he joined the Department of Pharmacology, New York Medical College in Valhalla as an instructor and, in 2000, he received internship and residency training at the Albert Einstein College of Medicine in New York before joining our program this year.  He has published 18 articles in peer review journals prior to joining our program including in KI, JPET, AJP and Hypertension, of which he is first or senior author on 7. Therefore, we considered him a very well-trained and experienced research physician and likely to benefit from research training in Nephrology.  Presently, he is undertaking one year of clinical training and we anticipate he will devote 2 years to research training under this grant, starting July 2006.