Kidney Disease Program
Program Leader: Benjamin Humphreys, MD, PhD
To watch a video about this program, click here.
Chronic kidney disease affects 7% of the population worldwide, with 1.6 million people suffering from end stage renal disease (ESRD). In the U.S. alone there are 450,000 patients with ESRD who require hemodialysis. The five-year survival of patients on dialysis is 33%, decidedly worse than the survival from many forms of cancer. The incidence of renal failure is projected to grow as obesity, poor nutrition, and lack of exercise increase the incidence of diabetes and hypertension. The cost of treating ESRD is currently $32 billion dollars annually, and is likely to double in the next decade. Similarly, acute kidney injury is a common medical problem with a significant impact on society. It results in an increased risk of death, a higher risk of future ESRD, longer hospital stays, and higher hospitalization costs. Current treatment options for acute and chronic kidney disease include dialysis, which is also associated with substantial morbidity and mortality, and kidney transplantation, which is limited by the supply of compatible organs.
The functional unit of the kidney is the nephron: each kidney comprises 500,000 nephrons, all of which are present at birth. One of the reasons renal failure is so common is the inability of our kidneys to form new nephrons. In contrast, some non-mammalian vertebrates continue to generate nephrons throughout their lives and produce new nephrons following renal injury. The focus of the HSCI Kidney Program is to understand the biology, differentiation, maintenance, repair, and diseases of the nephron, with the goal of developing new therapies. A specific emphasis is placed on one segment of the nephron, the proximal tubule, a particularly important region for normal function.
Understanding how non-mammalian vertebrates, like zebrafish, carry out their remarkable regenerative processes, and why mammals have lost this ability, is a fundamental biological question. Our scientists are working on generating zebrafish and mouse models of kidney injury to study the pathogenesis of acute kidney injury and chronic kidney disease, and to test new chemical compounds for therapeutic use.
Other researchers on our team are exploring the mechanisms of kidney development and repair to identify approaches to enhance normal repair mechanisms, and to incorporate novel strategies utilizing kidney stem/progenitor cells or fibroblasts to program critical cell types.
|Year||Principal Investigator||Institution||Project Title|
|2010||Aleksandr Vasilyev, MD, PhD||Massachusetts General Hospital||A Zebrafish Model of Acute Kidney Injury|
|M. Todd Valerius, PhD||Beth Israel Deaconess Medical Center||Transgenic Tools for Studies of the Proximal Nephron Tubule|
|Raghu Kalluri, MD, PhD||Beth Israel Deaconess Medical Center||Determining the Functional Contribution of Vascular Pericytes and Myofibroblasts in Tubular Regeneration and Interstitial Fibrosis|
|Xue Sean Li, PhD||Children's Hospital Boston||Precursors of the Proximal Tubule Epithelial Cells|
|2011||Iain Drummond, PhD||Massachusetts General Hospital||The Role of WNT Signaling in Kidney Tubule Regeneration|
|Andrew McMahon, PhD||Harvard Department of Stem Cell and Regenerative Biology||Trapping the Proximal Tubule in Acute Kidney Injury|
|Joseph Bonventre, MD, PhD||Brigham and Women's Hospital||Direct Reprogramming of Fibroblasts into Kidney Proximal Tubular Cells|
|Robert Handin, MD||Brigham and Women's Hospital||Epigenetic Regulation of Renal Stem Cell Proliferation in Zebrafish|
Extending the Program
Over the past couple of years the Kidney Program has funded multiple laboratories to pursue novel approaches within their main areas of research. Many investigators within the program have chosen to focus on the proximal tubule, and they meet regularly throughout the year to present the new data and seek each other’s advice. The Kidney Program further supports this by having prominent experts from around the world come to campus as part of HSCI’s Distinguished Speakers Forum and other events. The result is an active community of experts who share their knowledge as they tackle the critical questions posed by the complexity and challenges of kidney disease.