ACGME Fellowship Program - Research Preceptors

Dr. Fredric Coe and the Kidney Stone Research Group
(Dr. Elaine Worcester, Dr. Kristin Bergsland, and Dr. Anna Zisman)

The Kidney Stone Research Group is focused on achieving a better understanding of the processes that lead to kidney stone formation and determining ways to provide better prevention and treatment of stones. Protocols involving data mining from an extensive database of laboratory and clinical materials collected over four decades have helped to create a coherent sense of the disease for physicians world wide, and have complemented more basic studies in providing a clinical rationale. Recent discoveries have included the first convincing evidence that stone forming patients are hypertensive as a population. Additionally, human experimental protocols performed in the Clinical Research Center are aimed at understanding the pathogenesis of genetic hypercalciuria and have lead to the description of variability in proximal tubule function as a mechanism for the increased calcium excretion seen in these stone formers. Other interests include understanding the contribution of renal oxalate handling to the clinical risk of stone disease. Collaborations with Profs Andrew Evan and James Lingeman (Indiana University) involve study of papillary and deep medulla biopsies from stone forming patients obtained during percutaneous nephrolithotomy. This work has led to the discovery that renal stone disease begins as apatite plaque in the basements of thin loops of Henle, and to characterization of the physiological factors that control plaque formation.

Dr. Patrick Cunningham

Dr. Patrick Cunningham studies the mechanism of Acute Kidney Injury (AKI) using animal models and cell culture experiments, focusing on the importance of the renal endothelium. Specific areas of interest include the roles played by cytokines such as TNF, adhesion molecule expression, apoptosis, and the connection between caspase activation, cytoskeletal changes, and inflammatory signaling in renal endothelial cells. Methods used include tissue immunohistochemistry, confocal microscopy, use of siRNA transfection in cell culture, exploration of mouse renal hemodynamics with implantable flowprobes, and the technique of Blood Oxygen Level Dependence (BOLD)-MRI, as well as the use of mouse kidney transplantation to localize the influence of various mediators. Use of endothelial-specific gene knockout mice using a Cre-lox approach allows insights into the role of crucial mediators, such as TNFR1, within the vasculature during AKI. While especially interested in AKI in the setting of sepsis, Dr. Cunningham’s lab uses various models of renal injury including renal ischemia perfusion to test these hypotheses in other forms of AKI.

Dr. Mary Hammes

Dr. Mary Hammes has followed patients with end-stage renal failure on hemodialysis for several years. Her current research interests have been to study and improve vascular access for this patient population. She is interested in understanding the mechanism of venous stenosis in arteriovenous fistulae, specifically cephalic arch stenosis in patients with brachiocephalic fistula access.

Dr. Hatim Hassan

Dr. Hassan’s research focuses on elucidating the molecular mechanisms regulating SLC26A6, a key transporter in oxalate homeostasis, and how this regulation might pertain to the risk of hyperoxaluria and calcium oxalate kidney stone disease. Dr. Hassan has found that cholinergic signaling inhibits SLC26A6-mediated oxalate transport by human intestinal T84 cells through signaling pathways including the M3 muscarinic receptor, phospholipase C, PKC-δ and c-Src kinase. Ongoing research seeks to test the hypothesis that SLC26A6 activity is under cholinergic regulation in the intestine, and that changes in cholinergic (vagal) tone may thereby affect oxalate homeostasis, urinary oxalate excretion, and stone risk. His lab is also studying the roles of purinergic and serotonergic signaling, acting through PKC-δ, in the regulation of intestinal oxalate transport and how these signaling pathways might pertain to the risk of hyperoxaluria and calcium oxalate kidney stone disease. Using a diversity of cultured mammalian cells and whole animals, ongoing research utilizes a variety of techniques, including immunoblotting, immunoprecipitaion, cloning, real time PCR, site-directed mutagenesis, confocal microscopy, genomic approaches, and flux studies in cells and native intestinal tissues mounted in Ussing chambers (including measurements of paracellular permeability).

Dr. Michelle Josephson

Dr. Michelle Josephson studies medical complications of transplantation and donation including post transplant bone disease and BK nephropathy. Dr. Josephson also studies pregnancy in transplant recipients and kidney donors. Current research examines the risks for, prevention of, and best treatment strategies for BK nephropathy. As well, she works on prevention and management of bone disease after transplant.

Dr. Benjamin Ko

Dr. Ko studies the molecular mechanisms of hypertension. His work focuses on the sodium chloride cotransporter (NCC) in the distal convoluted tubule of the kidney, exploring the cellular events that lead to changes in NCC function. Current projects include examining the effects of hormones on NCC function as well as the role of ubiquitin in NCC regulation. This work is conducted primarily in a cell model system using techniques such as immunoblotting, immunohistochemistry, PCR, radiotracer uptake, and mass spectroscopy.

Dr. Orly Kohn

Dr. Orly Kohn is the Director of our Home Dialysis Unit and investigates the effects of daily hemodialysis and extended dialysis on clearance of solutes and toxins of various molecular sizes, blood pressure control and quality of life including sleep disorders.

Other research interests are factors which improve technique survival in peritoneal dialysis patients and preservation of residual renal function in dialysis patients.

Dr. Jay Koyner

Dr. Koyner has a clinical research focus in Critical Care Nephrology. His research group’s primary focus is on the diagnosis, care and treatment patient’s of acute kidney injury (AKI). AKI is an all too common occurrence in hospitalized patients, especially in the setting of critical illness / intensive care unit setting where despite the tremendous advances in understanding renal disease at the physiologic and molecular level it still carries an alarmingly high morbidity and mortality. As such, one of the group’s main projects is to better characterize the definition of AKI through the evaluation and investigation of a variety of novel plasma and urinary biomarkers of kidney injury in a variety of clinical settings. These studies will evaluate the biomarkers ability to provide not only an earlier diagnosis of AKI (compared to the current gold standard, serum creatinine) but also prognosticate the severity of the disease, as well as better define who is at greatest risk for long-term adverse (renal and non-renal) events. Similarly, Dr Koyner is involved in projects that explore potential prophylactic and therapeutic treatments for AKI in a variety of setting of critical illness (performed in collaboration with investigators from Pulmonary and Critical Care Medicine and Anesthesia Critical Care). As director of UCMC’s Inpatient Renal Replacement Therapy (RRT) Unit, he is performing studies investigating the optimal delivery of continuous RRT (CRRT) in the setting of the most severe forms of AKI. These studies include the examination of drug utilization and dosing in the setting of CRRT.

Dr. Bharathi Reddy

Dr. Reddy’s research interests include hypertension in CKD and hemodialysis as well as improving delivery of care and outcomes in patients with CKD and ESRD.

Dr. Anna Zisman

Dr. Anna Zisman studies the role of genetic differences in renal hemodynamics in CKD.