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RESEARCH

Our hope is that through research we will find ways of keeping tumors from forming, or at least keeping them small, and reduce the need for surgical intervention. With this end in mind, each year the VHL Family Alliance offers competitive grants to fund promising research that will lead to a cure for von Hippel-Lindau disease.

 


Research Grants Awarded in 2011

 

Disease-Causing Mutations

Eleanor Rattenbury A grant was awarded for Eleanor Rattenberry, a second-year Ph.D. student in the laboratory of Dr. Eamonn R. Maher, University of Birmingham, England, to study the DNA changes that alter the function of the VHL protein and inhibit its ability to suppress cell growth. Not all VHL gene DNA changes will cause VHL disease and so if a patient in whom VHL disease is a possibility, but not certain, is found to have a DNA change that has not been detected previously, it is often unclear whether that person has VHL disease (in which case their relatives are at risk and they may develop further tumors) or if it is just a rare but benign DNA variant. In such circumstances it would be very helpful to have a test (or tests) available that would reliably establish whether the change is disease-causing or not. This project seeks to develop tests that will directly assess the functions of the VHL protein and enable predictions regarding whether the DNA change causes disease or not, and if it is a disease-causing mutation, which tumors are likely to develop. This will not only be of practical benefit for patients undergoing VHL gene testing but will also inform on the relationships between the function of the VHL protein and tumor develop­ment. Better understanding of this relationship will be helpful for developing new therapies for VHL disease.

 

Understanding Drug Resistance in Renal Cell Carcinoma

A grant was awarded for Dr. Haifeng Yang of the Cleveland Clinic to study Drug Resistance in clear cell renal cell carcinoma (ccRCC). Mutations of the VHL tumor suppressor gene cause von Hippel-Lindau disease as well as sporadic ccRCC, the most common kidney cancer in the general population. Historically ccRCC has been resistant to all forms of traditional chemotherapy. VEGFR inhibitors generated positive clinical outcomes but not cures, so more drugs against new targets are needed. Suppression of a potent oncogene EGFR signifi­cantly blocked kidney tumor growth in mouse models, but EGFR inhibitors failed in kidney cancer patients. Recently it was found that a histone-modifying enzyme JARID1C was mutated in ccRCC. They found that when there is no VHL protein in the cell, JARID1C was responsible for the global reduction of an important epigenetic marker and suppression of some HIF-responsive genes. While HIF2a is an oncogene in ccRCC, promoting tumor growth, JARID1C is a tumor suppressor. When JARID1C was knocked down in ccRCC cells in a mouse model, the tumor grew significantly. HIF-dependent JARID1C activation also led to innate drug resistance to EGFR inhibitors in VHL-deficient kidney cancer cells.


Dr. Yang will investigate further the role of JARID1C and explore ways to defeat resistance so EGFR inhibitors could become useful drugs to VHL patients.

Haifeng Yang, PhD

With a total of over $1.3 million awarded to support research, previous grant recipients include

Donald Bellgrau, PhD
University of Colorado, Denver

Othon Iliopoulis, MD
Massachusetts General Hospital

Rupal Bhatt, MD, PhD
Beth Israel Deaconess Medical Center

Shahriar Koochekpour, MD, PhD
Louisiana State University Health Sciences Center

Robert D. Burk, MD
Albert Einstein College of Medicine of Yeshiva University

Thera P. Links, MD, PhD
University Medical Centre Groningen

Shufen Chen, MD, PhD
University of North Carolina

Eamonn R. Maher, MD, FRCP
University of Birmingham

Maria Czyzyk-Krzeska, MD, PhD
Univeristy of Cincinnati

Georges Mer, PhD
Mayo Clinic

Robert J. Duronio, PhD
University of North Carolina, Chapel Hill

Armin Pause, PhD
McGill University

Ian Frew, PhD
University of Zurich

Brenda Petrella, PhD
Dartmouth Medical School

Judith Frydman, PhD
Stanford Universtiy

Kimryn Rathmell, MD, PhD
University of North Carolina

Ehud Gazit, PhD
Tel Aviv University

William Rigby, MD
Dartmouth Medical School

Daniel J. George, MD
Duke University Medical Center

Andreea Ruxandra-Schmitzer, PhD
University of Montreal

Rachel Giles, PhD
University Medical Center Utrecht

Susanne Schlisio, PhD
Ludwig Institute for Cancer

James R. Gnarra, PhD
University of Pittsburgh Medical Center

Bin Teh, MD, PhD
Van Andel Institute

James Handa, MD
Johns Hopkins University School of Medicine

George V. Thomas, MD
Oregon Health and Science University’s Knight Cancer Institute

Tien Hsu, PhD
Boston University Medical Center

 


Research Grants Awarded by VHL Family Alliance
       
2010   2009   2008   2007   2006   2005   2004  2003   2002   2001   2000  1999  1998  1997

 

Research Reports
        2010   2009   2008   2007   2006   2005   2004   2003  2002   2001  2000  1999  1998   1997
 

Submitting a Research Proposal to VHLFA

 

Tools for Research

VHL Mutation Database Online - click here

  • Prepared by Dr. Christophe Béroud, French VHL Study Group, Montpellier, France
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Related Articles

Link between VHL and Kidney Cancer

 

[Last modified 22-Nov-2011]