Howard Donninger, Ph.D.

Research Program
Molecular Targets

Education
B.Sc., University of Cape Town, South Africa, 1990
B.Sc.(MED)(HONS), University of Cape Town, South Africa, 1991
Ph.D., University of Cape Town, South Africa, 2000

Research and Professional Experience
1999-2001
Post-doctoral Fellow, Department of Medicine, University of Stellenbosch, Tygerberg, Western Cape, South Africa

2001-2006
Post-doctoral Fellow, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

February - August, 2007
Research Associate, Division of Medical Biochemistry, Department of Clinical Laboratory Sciences, University of Cape Town, Western Cape, South Africa

2007-preent
Instructor, Division of Hematology/Oncology, Department of Medicine, University of Louisville, Louisville, KY

2007-present
Assistant Scientist, James Graham Brown Cancer Center, University of Louisville

Selected Awards and Professional Honors
1991-1995
South African Foundation for Research Development bursary, University of Cape Town, South Africa

1991-1996
Marion Beatrice Waddell Award, University of Cape Town, South African

1997
International Union of Biochemistry and Molecular Biology (IUBMB) Travel Fellowship

2000
Best clinical paper at the 3rd Annual Astrazeneca Medical Research Day, University of Stellenbosch, South Africa

2001
Medical Research Council (MRC) Post-doctoral Scholarship, University of Stellenbosh, South Africa

2005
Fellows Award for Research Excellence (FARE), National Cancer Institute

2009
Chair, Session III, Animal Models of RASSF1A; Clinical and Biological Implications for the Role of the RASSF Family of Tumor Suppressor Proteins, First International Symposium, Banff, Alberta, Canada

2011
Roger Herzig Jr. Faculty Research Price, 3rd place, James Graham Brown Cancer Center 10th Annual Retreat, Louisville, KY, US

Research Interest
Our lab is interested in the RASSF (RASSF1-6) family of Ras effectors and how they function as tumor suppressors.  The best characterized member of the family is RASSF1A whose expression is frequently inactivated in numerous tumor types by promoter methylation, an epigenetic mechanism that inactivates many tumor suppressor genes and is a major contributor to the development of cancer.  The RASSF proteins lack inherent enzyme activity and likely act as scaffolding molecules that facilitate the assembly of tumor suppressor complexes, thereby integrating multiple tumor suppressor pathways.  Although the family members share some homology, and thus some common functions, there is significant variation in their sequences to suggest that each has unique functions.  All the family members have a Ras binding domain and there is some evidence to suggest they do interact directly with the Ras oncoproteins.  In fact, we have shown that RASSF2 and K-Ras form an endogenous complex and K-Ras can modulate certain functions of RASSF2.  Thus the RASSF protein may link Ras to activation of pro-apoptotic pathways.  We are currently studying the interactions between the RASSF family members and other pro-apoptotic effectors to better understand how they impart their growth inhibitory properties on cells and how they potentially link Ras to apoptosis.

Publications

Donninger H, Allen N, Henson A, Pogue J, Williams A, Gordon L, Kassler S, Dunwell T, Latif F, Clark GJ.  Salvador protein is a tumor suppressor effector of RASSF1A with hippo pathway-independent functions.  J Biol Chem 286:18483-941, 2011

Donninger H, Hesson L, Vos M, Beebe K, Gordon L, Sidransky M, Liu JW, Schlegel T, Payne S, Hartmann A, Latif F, Clark GJ.  The Ras effector RASSF2 controls the PAR-4 tumor suppressor.  Mol Cell Biol 30:2608-20, 2010