George C. Prendergast

George C. Prendergast
Born	Philadelphia, Pennsylvania
Fields	Oncology, Molecular biology, Oncoimmunology
Institutions	Lankenau Institute for Medical Research DuPont Pharmaceuticals Company The Wistar Institute Merck Research Laboratories Howard Hughes Medical Institute
Alma mater	Princeton University (PhD) Yale University (MS) University of Pennsylvania (BA)
Notable awards	1995 Pew Scholar in the Biomedical Sciences

George C. Prendergast, PhD (born 1961) is an American oncologist and biomedical scientist, currently President and CEO of Lankenau Institute for Medical Research (LIMR);^[1] Co-leader of the Program in Cancer Cell Biology & Signaling at Kimmel Cancer Center, Thomas Jefferson University;^[2] and Editor-in-Chief of Cancer Research, the most highly cited journal in the field.^[3][4]

Education and Career

Born in Philadelphia, Pennsylvania in 1961, Prendergast graduated from the University of Pennsylvania in 1983 with a BA in Biochemistry. He earned an MS in molecular biophysics from Yale University in 1984 and a PhD in molecular biology from Princeton University in 1989.After receiving his doctorate, Prendergast continued his research as an American Cancer Society postdoctoral fellow at the Howard Hughes Medical Institute at NYU Medical Center.

Prendergast joined the Department of Cancer Research at Merck Research Laboratories as a staff scientist in 1991. In 1993, he returned to academic research at The Wistar Institute in Philadelphia, first as an assistant professor and later as an associate professor and assistant chair of the Tumor Biology Group. While at Wistar, in 1995, Prendergast was designated a Pew Scholar in the Biomedical Sciences.^[5]

In 1999, Prendergast left Wistar to become Senior Director of the Cancer Research Group at DuPont Pharmaceuticals Company. After the sale of DuPont Pharmaceuticals to Bristol-Myers Squibb, Prendergast moved his groups at Wistar and DuPont to Lankenau Institute for Medical Research (LIMR) in 2002. He was appointed President and CEO of LIMR in 2004,.

Accomplishments

Prendergast’s research has contributed to the discovery and study of oncogenes and tumor suppressor genes in cancer, and more recently to understanding the role of the immune system in cancer progression and treatment. In the field of cancer genetics, his research helped define how genetic alterations lead to cancer development.

Prendergast presenting at 2013 CIMT cancer immunotherapy conference in Mainz, Germany

His recent work has linked cancer genetics and cancer immunology in new ways and advanced the study of how cancer cells erect barriers against the immune system.^[6] Building on these insights, his research team at LIMR pioneered the discovery and development of IDO inhibitors, a new class of experimental oral drugs that degrade immune barriers erected by tumors and empower a patient’s immune system to attack tumors in combination with other therapies. Most recently, this area of work has illuminated new insights into autoimmunity and its treatment.

Prendergast is the author of over 200 peer-reviewed publications and 80 book chapters, editorials, and monographs. He has edited two books: Molecular Cancer Therapeutics: Strategies for Drug Discovery and Development (2004)^[7] and the first and second editions of Cancer Immunotherapy: Immune Suppression and Tumor Growth (2007, 2013). He currently serves as Editor-in-Chief of Cancer Research, the most-cited journal in the field.^[4]

His work has been cited over 15,000 times.^[8] Prendergast is an inventor on 19 U.S. patents, with additional international patents plus U.S. and international patents pending, and he has served as Founder, Director or Advisor of multiple biotech start-up companies.

Selected peer-reviewed publications (of 225 total)

Prendergast, G.C., and Ziff, E.B. (1991). “Methylation-sensitive sequence-specific DNA binding by the c-Myc basic region”. Science 250, 186-189. doi: 10.1126/science.1987636.

Prendergast, G.C., Lawe, D. and Ziff, E.B. (1991). "Association of Myn, the murine homolog of Max, with c-Myc stimulates methylation-sensitive DNA binding and Ras cotransformation". Cell 65, 395-407. doi: 10.1016/0092-8674(91)90457-A

Sakamuro, D., Elliott, K., Wechsler-Reya, R., and Prendergast, G.C. (1996). "BIN1 is a novel MYC-interacting protein with features of a tumor suppressor". Nature Genetics 14, 69-77. doi: 10.1038/ng0996-69.

Ge, K., DuHadaway, J., Du, W., Herlyn, M., Rodeck, U., and Prendergast, G.C. (1999). "Mechanism for elimination of a tumor suppressor:aberrant splicing of a brain-specific exon causes loss of function of Bin1 in melanoma". Proceedings of the National Academy of Sciences of the United States of America 96, 9689-9694.doi: 10.1073/pnas.96.17.9689.

Adini, I., Rabinovitz, I., Sun, J.F., Prendergast, G.C., and Benjamin, L.E. (2003). "RhoB controls Akt trafficking and stage-specific survival of endothelial cells during vascular development". Genes & Development 17, 2721-2732. doi: 10.1101/gad.1134603.

Muller, A.J., DuHadaway, J.B., Donover, P.S., Sutanto-Ward, E., and Prendergast, G.C. (2005). Inhibition of indoleamine 2,3-dioxygenase, a target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nature Med. 11, 312-319

Prendergast, G.C. and Jaffee, E.M. (2007). "Cancer immunologists and cancer cell biologists: why we didn’t talk then but need to now". Cancer Research 67, 3500-3505. doi: 10.1158/0008-5472.CAN-06-4626.

Metz, R., DuHadaway, J.B., Kamasani, U., Laury-Kleintop, L., Muller, A.J., and Prendergast, G.C. (2007). Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor IDO inhibitory compound D-1MT. Cancer Res. 67, 7082-7087. doi: 10.1158/0008-5472.CAN-07-1872

Muller, A.J., Sharma, M.D., Chandler, P.R., DuHadaway, J.B., Everhart, M., Johnson, B.A., Dahler, D.J., Pihkala, J., Soler, A.P., Munn, D.H., Prendergast, G.C.* and Mellor, A.L.* (2008). Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3-dioxygenase. Proc. Natl. Acad. Sci. USA 105, 17073-17078. doi: 10.1073/pnas.0806173105

Kumar, S., Jaller, D., Patel, B., LaLonde, J.M., DuHadaway, J.B., Malachowski, W.P., Prendergast, G.C. and Muller, A.J. (2008). Structure based development of phenylimidazole-derived inhibitors of indoleamine 2,3-dioxygenase. J. Med. Chem. 51, 4968-4977. doi: 10.1021/jm800512z

Prendergast, G.C. (2008). "Immune escape as a fundamental trait of cancer: focus on IDO". Oncogene 27, 3889-3900. doi: 10.1038/onc.2008.35.

Prendergast, G.C., Muller, A.J., Ramalingam, A. and Chang, M.Y. (2009). BAR the door: cancer suppression by amphiphysin-like genes. Biochim. Biophys. Acta. 1795, 25-36. doi: 10.1016/j.bbcan.2008.09.001

Prendergast, G.C., Metz, R. and Muller, A.J. (2010). "Towards a genetic definition of ‘cancer-associated’ inflammation: role of the IDO pathway". American Journal of Pathology 176, 2082-2087. doi: 10.2353/ajpath.2010.091173.

Smith, C., Chang, M.-Y., Parker, K., Beury, D., DuHadaway, J., Flick, H., Boulden, J., Sutanto-Ward, E., Soler, A.P., Laury-Kleintop, L., Mandik-Nayak, L., Metz, R., Ostrand-Rosenberg, S., Prendergast, G.C. and Muller, A.J. (2012). "IDO is a nodal pathogenic driver of lung cancer development and metastasis". Cancer Discovery 2, 722-735. doi: 10.1158/2159-8290.CD-12-0014.

Prendergast, G.C. (2012). "Immunological thought in the mainstream of cancer research: past divorce, recent remarriage and elective affinities of the future". OncoImmunology 1, 793-797. doi: 10.4161/onci.20909.

Metz, R., Rust, S., DuHadaway, J.B., Mautino, M.R., Munn, D.H., Vahanian, N.N., Link, C.J. and Prendergast, G.C. (2012). "IDO inhibits a tryptophan sufficiency signal needed to stimulate mTOR: a novel IDO effector pathway targeted by 1-methyl-D-tryptophan". OncoImmunology 1,1460-1468. doi: 10.4161/onci.21716.

Chang, M.-Y., Boulden, J., Valenzano, M.C., Soler, A.P., Muller, A.J., Mullin, J.M. and Prendergast, G.C. (2012). Bin1 attenuation suppresses inflammatory colitis by enforcing intestinal barrier function. Digest. Dis. Sci. 57, 1813-1821. doi: 10.1007/s10620-012-2147-y

Metz, R., Smith, C., DuHadaway, J.B., Chandler, P., Baban, B., Merlo, L.M.F., Pigott, E., Keough, M.P., Rust, S., Mellor, A.L., Mandik-Nayak, L., Muller, A.J. and Prendergast, G.C. (2014). IDO2 is critical for IDO1-mediated T cell regulation and exerts a non-redundant function in inflammation. Int. Immunol. 26, 357-367. doi: 10.1093/intimm/dxt073

Merlo, L.M.F., Pigott, E., DuHadaway, J.B., Grabler, S., Metz, R., Prendergast, G.C. and Mandik-Nayak, L. (2014). IDO2 is a critical mediator of autoantibody production and inflammatory pathogenesis in a mouse model of autoimmune arthritis. J. Immunol. 192, 2082-2090. doi: 10.4049/jimmunol.1303012

Prendergast, G.C., Smith, C., Thomas, S., Mandik-Nayak, L., Laury Kleintop, L.D., Metz, R. and Muller, A.J. (2014). Indoleamine 2,3-dioxygenase pathways in pathogenic inflammation and immune escape in cancer. Cancer Immunol. Immunother. 63, 721-735. doi: 10.1007/s00262-014-1549-4

Prendergast, G.C., Metz, R., Muller, A.J., Merlo, L.M.F. and Mandik-Nayak, L. (2014). IDO2 in immunomodulation and autoimmune disease. Front Immunol. 5, 585-590. doi: 10.3389/fimmu.2014.00585

Malachowski, W.P., Winters, M., DuHadaway, J.B., Lewis-Ballester, A., Badir, S., Wai, J., Rahman, M., Sheikh, E., Tadepalli, S., LaLonde, J., Yeh, S.-R., Prendergast, G.C. and Muller, A.J. (2015). O-alkyl hydroxylamines as rationally-designed mechanism-based inhibitors of indoleamine 2,3-dioxygenase-1. Eur. J. Med. Chem. 108, 564-576. doi: 10.1016/j.ejmech.2015.12.028

Thomas, S., Mercado, J.M., DuHadaway, J., DiGuilio, K., Mullin, J.M. and Prendergast, G.C. (2016). Novel colitis immunotherapy targets Bin1 to improve colon cell barrier function. Dig. Dis. Sci. 61, 423-432. doi: 10.1007/s10620-015-3804-8

Honors

1995 - American Cancer Society Junior Faculty Award
1995 - Pew Scholar in the Biomedical Sciences Award
2003 - Highlighted Project, 2003 DoD Prostate Cancer Research Program Report
2008 - Special Achievement Award, Chinese Society for Clinical Oncology
2008 - Designated One of the 250 Historically Most Influential Alumni of Princeton University^[9]
2012 - Inventor of the Year, Thomas Jefferson University Kimmel Cancer Center
2014 - Highlighted 'In the Pipeline' Project, DoD Breast Cancer Research Program Report
2016 - First Designee of the Endowed Havens Chair in Biomedical Research

References

External links

• George C. Prendergast on BioMed Experts
• Executive Leaders Radio Interview with George Prendergast, PhD, November 7, 2008.
• American Association for Cancer Research - Scientific Podcast Interview with George C. Prendergast, PhD, January 4, 2010.
• Comcast's Money Matters Interview with George C. Prendergast, PhD, December, 2012.