Jeffrey Michael Field, Ph.D.
1313 BRB II/III
University of Pennsylvania Perelman School of Medicine
Philadelphia, PA 19104-6084
Lab: (215) 898-1914
Columbia University, 1980.
M.A. (Molecular Biology)
Albert Einstein College of Medicine, 1983.
Ph.D. (Molecular Biology)
Albert Einstein College of Medicine, 1985.
Description of Research ExpertiseSystems Pharmacology of Ras signaling in cancer:
Mutations in genes called oncogenes lead to the uncontrolled growth that is the hallmark of cancer. Oncogenes express proteins that regulate signaling pathways essential to the tumor cell. We study the Ras oncogene, one of the most commonly mutated oncogenes. Mutational activation of Ras causes changes in three basic properties of cells. These are: (1) increases in cell proliferation to stimulate growth, (2) reorganization of the actin cytoskeleton to promote invasion and metastases and (3) inhibition of apoptosis to prevent tumor cells from undergoing programmed cell death. Previously, we studied Ras signaling in tumors focusing on the role of Pak kinases, providing the first proof-of-principle that Pak kinases are targets for new targeted therapies. Indeed, numerous companies and academic groups are developing small molecule inhibitors of Pak. More recently we developed a systems approach to study Ras tumors using genomics, high throughput screening and siRNA screening. Ongoing studies are validating lead compounds and genes identified in screens as well as developing new screening platforms. Despite some successes in targeting other oncogenes, Ras presently un-druggable and our screens promise to identify targets and validate drugs against Ras in several cancer models.
Cytoskeletal signaling pathways:
We discovered a family of proteins in yeast known as cyclase associated proteins (CAP). In yeast, they are required for Ras signaling, but in mammalian cells, they participate in cytoskeletal signaling. Current studies with CAP use in vivo models to study CAP2 function in cardiac physiology and signaling.
Mechanisms of environmental toxicology:
We also use a systems approach to study environmental toxicology. Past work linked one of the most potent carcinogens in tobacco with the most widely reported stress in smokers—oxidative stress.
I direct two graduate courses (Pharm 623 and Pharm 495). Pharm 495 teaches high throughput screening using a hands-on approach to systems cancer biology. I also direct the TREES summer program for High School students and the STEER summer program for college students, two community outreach programs that provide mentoring opportunities for graduate students.
Selected PublicationsXiong Yao, Bedi Ken, Berritt Simon, Attipoe Bennette K, Brooks Thomas G, Wang Kevin, Margulies Ken B, Field Jeffrey: Targeting MRTF/SRF in CAP2-dependent dilated cardiomyopathy delays disease onset. JCI Insight 4(6), Mar 2019.
Guo Jianman, Grovola Michael R, Xie Hong, Coggins Grace E, Duggan Patrick, Hasan Rukhsana, Huang Jiale, Lin Danny W, Song Claire, Witek Gabriela M, Berritt Simon, Schultz David C, Field Jeffrey: Comprehensive pharmacological profiling of neurofibromatosis cell lines. American journal of cancer research 7(4): 923-934, 2017.
Lu Hezhe, Liu Shujing, Zhang Gao, Bin Wu , Zhu Yueyao, Frederick Dennie T, Hu Yi, Zhong Wenqun, Randell Sergio, Sadek Norah, Zhang Wei, Chen Gang, Cheng Chaoran, Zeng Jingwen, Wu Lawrence W, Zhang Jie, Liu Xiaoming, Xu Wei, Krepler Clemens, Sproesser Katrin, Xiao Min, Miao Benchun, Liu Jianglan, Song Claire D, Liu Jephrey Y, Karakousis Giorgos C, Schuchter Lynn M, Lu Yiling, Mills Gordon, Cong Yusheng, Chernoff Jonathan, Guo Jun, Boland Genevieve M, Sullivan Ryan J, Wei Zhi, Field Jeffrey, Amaravadi Ravi K, Flaherty Keith T, Herlyn Meenhard, Xu Xiaowei, Guo Wei: PAK signalling drives acquired drug resistance to MAPK inhibitors in BRAF-mutant melanomas. Nature 550(7674): 133-136, Oct 2017.
Field J, Ye DZ, Shinde M, Liu F, Schillinger KJ, Lu M, Wang T, Skettini M, Xiong Y, Brice AK, Chung DC, Patel VV: CAP2 in cardiac conduction, sudden cardiac death and eye development. Sci Rep 5: 17256, Nov 2015.
Licciulli, S., Maksimoska, J., Zhou, C., Troutman, S., Kota, S., Liu, Q., Duron, S., Campbell, D., Chernoff, J., Field, J., Marmorstein, R., Kissil, J. L.: FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of NF2-associated schwannomas. J Biol Chem 288: 29105-29114, 2013.
Ye, Diana Zi, Field, Jeffrey: PAK signaling in cancer. Cellular Logistics. Landes Bioscience Inc. 2(2): 105-116, 2012.
Sen, Sushmita, Bhojnagarwala, Pratik, Francey, Lauren, Lu, Ding, Penning, Trevor M., Field, Jeffrey: p53 Mutagenesis by Benzo[a]pyrene Derived Radical Cations. Chemical Research in Toxicology. American Chemical Society, 25(10): 2117-2126, 2012.
Park J-H, Gelhaus S, Vedantam S, Oliva AL, Batra A, Blair IA, Troxel AB, Field J, Penning TM: The pattern of p53 mutations caused by PAH o-quinones is driven by 8-oxo-dGuo formation while the spectrum of mutations is determined by biological selection for dominance. Chem Res Toxicol 21: 1039-1049, 2008.
Williams J, Su HS, Bernards A, Field J, Sehgal A: A circadian output in Drosophila mediated by neurofibromatosis-1 and Ras/MAPK. Science 293: 2251-2256, 2001.
Tang Y, Marwaha S, Rutkowski JL, Tennekoon GI, Phillips PC, Field J: A role for Pak protein kinases in Schwann cell transformation. Proc Natl Acad Sci USA 95: 5139-5144, 1998.