beth israel deaconess medical center a harvard medical school teaching hospital

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Investigators

The Division and faculty members who are related closely to it perform ground-breaking research in a wide variety of areas related to renal physiology and kidney disease.  

Renal Physiology:


Ion and water transport. The laboratories of Drs. AlperZeidel and Epstein are studying the molecular physiology and roles of bicarbonate and chloride transport in the regulation of cell and systemic pH and volume, potassium homeostasis in red cell hemoglobinopathies and in secretory epithelia, how water, protons and small non-electrolytes cross biological membranes and how intracellular signaling pathways modulate the secretion of chloride by rectal glands of elasmobranchs. The  Alper laboratory is also studying the deficient shear/flow signaling phenotype of human PKD cyst cells of defined mutant genotype, and contributions of oxalate transport to nephrolithiasis.

Quantification of renal function. Dr.  Mandelbrot is involved in research on novel technologies for measuring renal function. He has described the use of neutron activation to measure glomerular filtration rate and future studies will use this method to measure renal blood flow.

Glomerular physiology and development of proteinuria.  Karumanchi and Mutter have generated microarray data from podocytes grown in high and normal glucose in studies aimed at deciphering novel targets and pathways. Transcriptional profiles of podocytes lacking nephrin (mutated in congenital Finnish nephrotic syndrome) and LMX-1b (mutated in Nail-Patella Syndrome) are in progress. Urine proteomics data from diabetic patients with and without nephropathy are being analyzed in order to identify novel urine markers that predict worse renal outcomes. Dr. Mutter is investigating soluble mediators of proteinuria in Minimal Change Disease as well as the mechanisms of proteinuria in preeclampsia.

Renal Autoregulation. Dr.  Friedman is studying how the kidney regulates renal vascular resistance in response to changes in perfusion pressure. Using mouse models that have defective renal autoregulation, he is studying how this mechanism protects the kidney against injury in diabetes, hypertension, and after reduction of nephron number.

Acute kidney injury:


Acute renal failure. Studies in acute renal injury by Dr. Parikh focus on a novel animal model of sepsis-induced acute kidney injury as well as a cohort study of acute renal failure patients at BIDMC. 

Chronic kidney disease:


Kidney hypoxia and chronic kidney disease. Dr. Epstein continues to investigate oxygenation levels of renal tissue in patients with chronic renal disease by magnetic resonance to test the hypothesis that hypoxia plays a key role in the progression of chronic renal failure.

Molecular mechanisms of muscle atrophy. Dr. Lecker's research explores the molecular mechanisms behind the muscle wasting which occurs in uremia and other chronic illnesses such as cancer, sepsis and diabetes. Dr. Lecker's studies have identified a group of about 100 genes (termed "atrogenes") that are coordinately regulated during wasting. His work now focuses on the function of one of those genes, called atrogin-1. A recent collaboration with Dr.  Sukhatme has shed new light into the mechanisms of statin induced myopathy, which they have discovered is mediated by atrogin-1.

Vitamin K dependent proteins (VKDPs) and vascular calcification. Dr. Danziger is studying the role of VKDPs in vascular and skeletal biology. Ongoing clinical research is aimed at understanding the role of VKDPs in vascular calcification in patients with underlying chronic kidney disease, as well as their importance in preventing osteoporosis in patients with gastrointestinal malabsorptive conditions. In collaboration with Dr. Beate Lanske, basic research projects to understand the molecular mechanisms of vascular calcification are being pursued.

Mineral ion homeostasis. New efforts by Dr. Egbuna to understand mineral ion regulation by the calcium-sensing receptor independent of parathyroid hormone are under investigation, as are studies of the role of this receptor in immune cells.

Anemia in ESRD. Dr. Mutter is currently investigating the role of the soluble erythropoietin receptor in anemia of end stage renal disease.

Vascular biology:


Preeclampsia, vascular leak, tumor angiogenesis. Karumanchi's research aims at defining the pathophysiology of preeclampsia and vascular leak syndromes through a molecular understanding of the circulating receptor fragments s-flt1 and endoglin. Dr.  Parikh is studying the role of the angiopoietin family of ligands in vascular leak syndromes in man. A translational focus has been on clinical trials of novel anti-angiogenesis drug combinations for cancer therapy ( Sukhatme). A novel role for the orphan endothelial specific receptor Tie-1 in atherosclerosis has been elucidated, as have downstream signaling pathways ( Sukhatme).

Diabetic renal disease:


Oxidant damage, diabetic vascular disease and cancer progression. Dr. Stanton's laboratory has focused on elucidating the regulation of glucose 6-phosphate dehydrogenase (G6PD), the main source of NADPH, the principal reductant in the cell. Dr. Stanton's research has shown that diabetes causes a major decrease in the activity of G6PD, and that G6PD plays critical roles in the regulation of cell growth and cell death (apoptosis). A key role of aldosterone in impairing vascular reactivity through diminishing G6PD has been recently elucidated.

Purinergic signaling. Dr. Friedman's research focuses on the role of purinergic signaling (ectonucleotidases and purinergic receptors) in vascular disease. Using mouse models, he is investigating microvascular injury in diabetic nephropathy and large vessel disease in studies of arteriovenous fistula maturation and stenosis.

Matrix biology and the kidney:


BIDMC recently created a Center for Matrix Biology to bring together diverse researchers interested in the biology of basement membranes and extracellular matrix in health and disease. Its director, Raghu Kalluri, has broad interests in matrix biology, especially as it pertains to genetic and acquired renal diseases involving basement membranes. Dr. Michael Zeisberg is studying the epigenetics of chronic kidney disease to understand how epigenetic modifications cause fibroblast activation and ultimately lead to renal fibrosis. He is also exploring how the endogenous protein, BMP7, protects the kidney from injury. Dr. Elisabeth Zeisberg is researching the process of endothelial to mesenchymal transition and how it promotes tissue fibrosis or scarring, especially in the kidney.

Renal Pathology:

Dr. Isaac Stillman and Dr. Seymour Rosen are recognized world leaders in renal pathology. They are both involved in research projects in collaboration with other members of the renal faculty including Drs. Karumanchi, Epstein and Friedman.

Transplantation:


Tolerance and rejection. An understanding and clinical application of immune tolerance is the primary goal of the  Strom laboratory. The balance of activated effector to regulatory cells can be manipulated through signals that are triggered by specially designed cytokine related Ig fusion proteins crafted in the Strom laboratory or through activation of select members of the T cell immunoglobulin family of proteins.

Islet Transplantation. Islet Transplantation is at BIDMC as part of the center for Islet Transplantation at Harvard Medical School. Dr.  Pavlakis and colleagues are currently enrolling patients with diabetes who have received a kidney transplant.

Drug trials in renal transplantation. Drs. Pavlakis, Mandelbrot, and Egbuna remain active in this area. Strategies to reduce calcineurin nephrotoxicity in renal transplant patients, the optimal management of hepato-renal patients, including liver transplantation, and IL-2 receptor blockade to prevent rejection of renal transplants are under investigation.

Prediction of kidney transplant outcome. Dr. Goldfarb uses national collection of data to evaluate factors predicting renal transplant outcome (dialysis course, socio-economic characteristics, comorbidities) and to develop mathematical models predicting graft and recipient survival. Information regarding genetic predictors of transplant outcome is being collected.

Disparity in Living Kidney Transplantation rates among African Americans. Drs. EgbunaMandelbrot and  Pavlakis are involved in an NIH sponsored trial to reduce the rates of disparity in African Americans.