2009 NephCure Funded Investigators

Post-Doctoral Fellowship Grants were awarded to:
•    Sebastian Martini, University of Michigan, Ann Arbor, MI
•    Hideki Kato, Albert Einstein College of Medicine, Bronx, NY

Young Investigator Grants were awarded to:
•    Christian Faul, University of Miami, Miami, FL
•    Kirk Campbell, University of Miami, Miami, FL
•    Mira Krendel, SUNY Upstate Medical University, Syracuse, NY
•    Valerie Anne Schumacher, Children’s Hospital Boston, Boston, MA

Established Investigator Grant awarded to:
•    Sanja Sever, Massachusetts General Hospital, Charleston, MA

Hideki Kato MD, PhD – The Dual Role of Beta-catenin in Podocytes
Research indicates that injury to specialized kidney cells, podocytes, plays a pivotal role in the disease. Previous studies from Dr. Kato’s lab indicate that the protein, beta-catenin, plays a role in the maintenance of the structure of the filtering units of the kidneys. Dr. Kato will study beta-catenin to better understand how it can lead to FSGS and proteinuria (leakage of protein into urine).

Christian Faul, PhD – The Function of Calcineurin Signaling in Podocytes
Calcineurin is a protein that is expressed in all tissues and inhibited by cyclosporine A (CsA), an immunosuppressant drug used to treat kidney diseases such as FSGS. Dr. Faul’s research will characterize the function of calcineurin in podocytes (specialized kidney cells) at the transition from early and reversible to late and chronic damage which could serve as a promising target for kidney diseases.

Valerie Anne Schumacher PhD – Post-transcriptional Regulation of Gene Expression in Glomerular Disease
Dr. Schumacher’s research aims to clarify how mutations in the protein WT1 found in podocytes (specialized cells in the kidney) result in steroid resistant NS that rapidly progresses to FSGS and eventually end stage renal disease. These studies can lead to novel treatments to prevent podocyte damage and promote repair in FSGS.

Kirk Campbell MD – Regulation of Podocyte Survival by Dendrin
Podocytes (specialized kidney cells) have attachments help form the barrier to urinary protein loss. Damage to these cells may result in proteinuria (loss of proteins into the urine) and several kidney disorders resulting in the death and loss of podocytes. Dr. Campbell’s research will focus on the protein dendrin, and its role in regulation of podocyte survival in mouse models of FSGS.

Mira Krendel PhD – The Role of Myosin 1e-synaptopodin Interaction in Podocyte Function
Dr. Krendel has found that mutations in the protein, myosin 1e, results in severe defects in filtration of the blood to produce urine. Additionally, myosin 1e interacts with another protein, synaptopodin, an important regulator of podocytes (specialized kidney cells). Dr. Krendel will establish the mechanism by which myosin 1e loss results in podocyte dysfunction and kidney disease.

Sanja Sever PhD – The Role of GTPase Dynamin in Foot Process Effacement
Podocytes (special kidney cells) form foot processes, cellular extensions. Most forms of NS are characterized by reduction of these extensions and their reorganization. Dr. Sever’s research focuses on the mechanism that leads to podocyte effacement or reorganization. Additionally, Dr. Sever will elucidate the role of the protein dynamin as a regulator of podocytes.

Other grants were awarded by The NephCure Foundation and Donors:
•  “Biobank” for NS and FSGS –  Matthias Kretzler MD, University of Michigan
•  Clinical Study of Oral Galactose for FSGS – Howard Trachtman MD, Schneider Children’s Hospital
•  Endowed University Chair – Pediatric Nephrology in FSGS, University of Michigan
•  MGH Glomerular Center Dynamin Project – Jochen Reiser MD, PhD and Sanja Sever PhD
•  Molecular Genetics Nephrotic Syndrome – Rasheed Gbadegesin MD, Michelle Winn MD, Duke University   Center for Human Genetics
•  Nephrotic Syndrome Rare Diseases Clinical Research Consortium

“Biobank” for NS and FSGS
Dr. Matthias Kretzler is creating a “Registry” for Nephrotic Syndrome and FSGS. It is a collection of biopsy tissues and specimens from patients with the disease, as well as histories. This will be used to develop a system of markers to subdivide different forms of FSGS providing finer details as to prognosis, responsiveness to various drugs, and why some patients fail to respond to treatment.

Clinical Study of Oral Galactose
One theory as to the cause of primary FSGS, supported by evidence of recurrence of FSGS in patients following kidney transplant, is the presence of increased levels of permeability factors that enhance the leakage of protein into the urine. Based on preliminary investigations a sugar, galactose has been found that may bind to the permeability factor. NF is supporting this pilot proof-of-concept study to determine if oral administration of galactose lowers the level of a circulating permeability factor in patients with FSGS.

Endowed University Chair
The Robert C. Kelsch Collegiate Chair in Pediatric Nephrology at the University of Michigan was endowed with major support from a NephCure Founder. The Head of the Section of Pediatric Nephrology at Michigan traditionally holds the Chair. All proceeds from the Chair’s endowment are earmarked for basic research into the molecular mechanisms of FSGS and Minimal Change.

MGH Glomerular Center Dynamin Project
Jochen Reiser MD, PhD, at the University of Miami Medical School, along with Sanja Sever PhD, at Massachusetts General Hospital have uncovered how a certain protein – dynamin -- retains the healthy structure of the podocyte. Some forms of the enzyme cathepsin (CatL) have a positive role in the body; they have determined that one form can lead to destruction of the podocyte causing proteinuria. Experiments will focus on developing therapies to block only that portion of CatL which destroys the podocyte foot processes.

Molecular Genetics of Nephrotic Syndrome
Rasheed Gbadegesin, MD and Michele Winn, MD collaborate in a research laboratory at Duke University where the focus will be on sporadic cases of FSGS. While the etiology is uncertain, it is possible that it is due to interaction between the environment, infectious agents and multiple genetic defects. The team proposes to identify cases of sporadic FSGS from their center and cases from the Chronic Kidney Disease in Children study and perform genome wide association studies to identify disease loci and risk factors for disease progression.

Nephrotic Syndrome Rare Diseases Clinical Research Consortium
NephCure has joined with 15 universities in collaboration towards the establishment of this Consortium, a multidisciplinary research and education platform aimed at further studying Glomerular diseases such as FSGS, and MCD. This $10 million five year grant ($6 million provided by the National Institute of Health Office of Rare Disease, $2 million from NCF and $2 million in-kind from the University of Michigan) has been approved to begin in the fall of 2009. The specific aims of the Consortium are as follows:

1.  To establish an infrastructure to efficiently conduct clinical and translational research in NS
2.  To identify biomarkers (used for the diagnosis of disease) and potential targets for NS
3.  To conduct two clinical studies in NS
4.  To implement a program to train those with MD/PhD in conducting research in kidney disease
5.  To develop multimedia lay and physician educational resources on NS
6.  To develop a secured repository of clinical data and biospecimens of NS patients for sharing among researchers thus stimulating research into these diseases internationally

For more information see www.nephcure.org or you can contact us at info@nephcure.org