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Jonathan Chernoff, MD, PhD
This Fox Chase professor participates in the Undergraduate Summer Research Fellowship.
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Research Program
Lab Overview
The process of neoplastic transformation can be conceptually divided into two components. The first of these, proliferative transformation, refers to the ability of transformed cells to bypass growth suppression signals, suriviving and dividing when normal cells would not. The second, morphologic transformation, refers to loss of normal cytoskeletal architecture, often accompanied by decreased adhesion and acquisition of the ability to invade surrounding tissues. These two fundamental properties are intimately linked to one another, although experimentally they can be dissected apart through the use of gain-of-function and loss-of-function manupulation of signaling molecules. The overall focus this research is in uncovering the roles of protein phosphorylation in governing these two fundamental aspects of cancer biology.
Bio
As Cancer Center Director at Fox Chase Cancer Center, Jonathan Chernoff works with Temple University Health System and Temple University peers to lead Fox Chase into the future of cancer care. With decades of research expertise, Chernoff has helped Fox Chase focus on the areas that best leverage the institution’s enhanced strengths in scientific development: translational research, precision medicine, epigenetics, signaling reprograming, immunotherapy, hematologic malignancies, and cancer disparities.
A molecular oncologist and board-certified medical oncologist, Chernoff joined Fox Chase in 1991. In addition to helping define the strategic direction for Fox Chase research, he has made fundamental contributions in his own laboratory, which focuses on factors that control cell growth and movement, including oncogenes and anticancer or tumor-suppressor genes. He currently holds the Stanley P. Reimann Chair in Oncology Research.
Chernoff has trained dozens of postdoctoral and graduate students at Fox Chase. He serves as an adjunct professor for the Drexel University School of Medicine and for the University of Pennsylvania, and is a member of the Cancer Signaling and Epigenetics research program at Fox Chase.
In addition to these roles, Chernoff has served on multiple external advisory boards, including the Scientific Advisory Board for Nexgenix Pharmaceuticals, as well as advisory boards for Genentech, Novartis Pharmaceuticals, and the New York University (Perlmutter) Cancer Center, among others. He has also taken on roles for multiple committees and programs within Fox Chase.
Chernoff earned his bachelor’s degree in molecular biophysics and biochemistry from Yale College and his medical degree and doctorate from the Mount Sinai School of Medicine in New York. He completed his residency in internal medicine at the University Health Center of Pittsburgh and a clinical fellowship in medical oncology at Johns Hopkins Oncology Center. He then held a postdoctoral fellowship in cellular and developmental biology at Harvard University before coming to Fox Chase.
Educational Background
- PhD, Biochemistry, Mt. Sinai School of Medcine, New York, NY, 1984
- MD, Biochemistry, Mt. Sinai School of Medcine, New York, NY, 1984
- BA, Molecular Biophysics and Biochemistry, Yale College, New Haven, CT, 1978
Honors & Awards
- Faculty of 1000 (2007-present)
- Stanley P. Reimann Chair in Oncology research (2008-present)
- Fellow, American Association for the Advancement of Science (AAAS) (2017)
- AACR, Educational Session Leader (2014)
- Pennsylvania Drug Discovery Institute, Drug Discovery Award (2013)
- Senior Fellow, American Asthma Assn (2008-2011)
- Chair: NF2 Preclinical Consortium (2011-2012)
- American Cancer Society, Southeast PA division, Scientific Research Award (2010)
- Vice-Chair, FASEB “Small GTPases” (2008)
- Chair, GRC “Mechanisms of Cell Signaling (2007)
- Dozor Lecturer, Ben-Gurion University, Israel (2007)
- Leukemia Society of America Scholar Award, (1997-2002)
- ACS Research Scholar (1993-1998)
- W.W. Smith Charitable Trust Fellowship 1993-1996
- Pfizer Traveling Fellow (1996)
- B.S. cum laude, Yale University (1978)
People
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Cristina Uribe-Alvarez, PhDPostdoctoral AssociateW450 -
Dorothy Benton, BSGraduate Student, Drexel University College of MedicineW450 -
Konstantin Budagyan, BSGraduate Student, Drexel University College of MedicineW451 -
Alexa Cannon, BSGraduate Student, Drexel University College of MedicineW450 -
Sofiia Karchugina, MDGraduate Student, Pirogov Russian National Research Medical UniversityW451 -
Anne CarsonSenior Administrative Assistant to Jonathan Chernoff, MD, PhD, Chief Scientific OfficerW455
Research Interests
- Rac1 signaling in malignant melanoma
- Regulation and role of p21-activated kinases in cancer
- Hippo tumor suppressor pathway
- Kras isoform-specific signaling
Lab Overview
The process of neoplastic transformation can be conceptually divided into two components. The first of these, proliferative transformation, refers to the ability of transformed cells to bypass growth suppression signals, surviving and dividing when normal cells would not. The second, morphologic transformation, refers to loss of normal cytoskeletal architecture, often accompanied by decreased adhesion and acquisition of the ability to invade surrounding tissues. These two fundamental properties are intimately linked to one another, although experimentally they can be dissected apart through the use of gain-of-function and loss-of-function manipulation of signaling molecules. The overall focus this research is in uncovering the roles of key protein kinases that govern these two fundamental aspects of cancer biology.
Selected Publications
Karchugina S., Benton D.,Chernoff J., Regulation of mst complexes and activity via sarah domain modifications. Biochem Soc Trans. 49(2): 675-683, 2021. https://www.ncbi.nlm.nih.gov/pubmed/33860801.
Benton D.,Chernoff J., A new rho(d) map to diffuse gastric cancer. Cancer Discov. 10(2): 182-184, 2020. PMC7079203. https://www.ncbi.nlm.nih.gov/pubmed/32024682.
Cannon A.C., Uribe-Alvarez C.,Chernoff J., Rac1 as a therapeutic target in malignant melanoma. Trends Cancer. 6(6): 478-488, 2020. PMC7380552. https://www.ncbi.nlm.nih.gov/pubmed/32460002.
Binder P., Wang S., Radu M., Zin M., Collins L., Khan S., Li Y., Sekeres K., Humphreys N., Swanton E., Reid A., Pu F., Oceandy D., Guan K., Hille S.S., Frey N., Muller O.J., Cartwright E.J., Chernoff J., Liu W., Wang X., Pak2 as a novel therapeutic target for cardioprotective endoplasmic reticulum stress response. Circ Res. 124(5): 696-711, 2019.PMC6407830. 15.862
Chernoff J., How much is my paper worth? Mol Biol Cell. 30(23): 2878-2879, 2019. PMC6822591. 3.905
Kurimchak A.M., Shelton C., Herrera-Montavez C., Duncan K.E., Chernoff J., Duncan J.S., Intrinsic resistance to mek inhibition through bet protein mediated kinome reprogramming in nf1-deficient ovarian cancer. Mol Cancer Res. 17(8): 1721-1734, 2019. PMC6679760. 4.484
Lu H., Liu S., Zhang G., Wu B., Zhu Y., Frederick D.T., Hu Y., Zhong W., Randell S., Sadek N., Zhang W., Chen G., Cheng C., Zeng J., Wu L.W., Zhang J., Liu X., Xu W., Krepler C., Sproesser K., Xiao M., Miao B., Liu J., Song C.D., Liu J.Y., Karakousis G.C., Schuchter L.M., Lu Y., Mills G., Cong Y., Chernoff J., Guo J., Boland G.M., Sullivan R.J., Wei Z., Field J., Amaravadi R.K., Flaherty K.T., Herlyn M., Xu X. ,Guo W., Author correction: Pak signalling drives acquired drug resistance to mapk inhibitors in braf-mutant melanomas. Nature. 565(7738): E4, 2019. 43.070
Sannai M., Doneddu V., Giri V., Seeholzer S., Nicolas E., Yip S.C., Bassi M.R., Mancuso P., Cortellino S., Cigliano A., Lurie R., Ding H., Chernoff J., Sobol R.W., Yen T.J., Bagella L., Bellacosa A., Modification of the base excision repair enzyme mbd4 by the small ubiquitin-like molecule sumo1. DNA Repair. 82: 102687, 2019.PMC6785017. 3.711
Araiza-Olivera D. ,Chernoff J., Hras helps hippo heterodimerize to evade tumor suppression. Small GTPases. 9(4): 327-331, 2018. PMC5997136.
Chow HY, Dong B, Valencia CA, Zeng CT, Koch JN, Prudnikova TY, Chernoff J. Group I Paks are essential for epithelial- mesenchymal transition in an Apc-driven model of colorectal cancer. Nature communications, 9(1):3473, 2018. PMC6110733
Karchugina S., Chernoff J., Detection of heterodimerization of protein isoforms using an in situ proximity ligation assay. J Vis Exp, (140)2018. PMC6235567. 1.108
Kim S.M., Nguyen T.T., Ravi A., Kubiniok P., Finicle B.T., Jayashankar V., Malacrida L., Hou J., Robertson J., Gao D., Chernoff J., Digman M.A., Potma E.O., Tromberg B.J., Thibault P.,Edinger A.L., Pten deficiency and ampk activation promote nutrient scavenging and anabolism in prostate cancer cells. Cancer Discov. 8(7): 866-883, 2018. PMC6030497. 26.370
Stepanova D.S., Braun L., Chernoff J., A new concept in nf2 pharmacotherapy: Targeting fatty acid synthesis. Oncoscience. 5(5-6): 126-127, 2018. PMC6049319.
Prudnikova T.Y., Chernoff J., The group i pak inhibitor frax-1036 sensitizes 11q13-amplified ovarian cancer cells to the cytotoxic effects of rottlerin. Small GTPases. 8(4): 193-198, 2017. PMC5680705. 2.048
Semenova G., Chernoff J., Targeting pak1. Biochem Soc Trans. 45(1): 79-88, 2017. PMC5973817. 4.291
Semenova G., Stepanova D., Deyev S.M., Chernoff J., Medium throughput biochemical compound screening identifies novel agents for pharmacotherapy of neurofibromatosis type i. Biochimie. 135: 1-5, 2017. PMC5405558. 3.362
Araiza-Olivera D, Feng Y, Semenova G, Prudnikova TY, Rhodes J, Chernoff J. Suppression of RAC1-driven malignant melanoma by group A PAK inhibitors. Oncogene, 37(7):944-52, 2018. PMC5814328
Semenova G, Stepanova DS, Dubyk C, Handorf E, Deyev SM, Lazar AJ, Chernoff J. Targeting group I p21-activated kinases to control malignant peripheral nerve sheath tumor growth and metastasis. Oncogene, 36(38):5421-31, 2017. PMC5608634
Stepanova DS, Semenova G, Kuo YM, Andrews AJ, Ammoun S, Hanemann CO, Chernoff J. An essential role for the tumor suppressor Merlin in regulating fatty acid synthesis. Cancer Res, 77(18):5026-38, 2017. PMC5600854
Effects of p21-activated kinase 1 inhibition on 11q13-amplified ovarian cancer cells. Prudnikova TY, Villamar-Cruz O, Rawat SJ, Cai KQ, Chernoff J. Oncogene. 2015 Aug 10. doi: 10.1038/onc.2015.278. PMID:26257058
Kosoff RE, Aslan JE, Kostyak JC, Dulaimi E, Chow HY, Prudnikova TY, Radu M, Kunapuli SP, McCarty OJ, Chernoff J. Pak2 restrains endomitosis during megakaryopoiesis and alters cytoskeleton organization. Blood. 2015 May 7;125(19):2995-3005. doi: 10.1182/blood-2014-10-604504. Epub 2015 Mar 30. PubMed PMID: 25824689; PubMed Central PMCID: PMC4424419.
Regulation of mammalian Ste20 (Mst) kinases. Rawat SJ, Chernoff J. Trends in biochemical sciences. 2015; 40(3):149-56. NIHMSID: NIHMS655499 PubMed PMID: 25665457 PMCID:PMC4340714.
Chow HY, Dong B, Duron SG, Campbell DA, Ong CC, Hoeflich KP, Chang LS, Welling DB, Yang ZJ, Chernoff J. Group I Paks as therapeutic targets in NF2-deficient meningioma. Oncotarget. 2015 Feb 10;6(4):1981-94. PubMed PMID: 25596744; PubMed Central PMCID: PMC4385830.
Kelly ML, Astsaturov A, Rhodes J, Chernoff J. A Pak1/Erk signaling module acts through Gata6 to regulate cardiovascular development in zebrafish. Dev Cell. 2014 May 12;29(3):350-9. doi: 10.1016/j.devcel.2014.04.003. PubMed PMID: 24823378; PubMed Central PMCID: PMC4073496.
PAK signalling during the development and progression of cancer. Radu M, Semenova G, Kosoff R, Chernoff J. Nature reviews. Cancer. 2014; 14(1):13-25. NIHMSID: NIHMS556174 PubMed PMID: 24505617 PMCID: PMC4115244.
Pak1 kinase links ErbB2 to β-catenin in transformation of breast epithelial cells. Arias-Romero LE, Villamar-Cruz O, Huang M, Hoeflich KP, Chernoff J. Cancer research. 2013; 73(12):3671-82. NIHMSID: NIHMS464433 PubMed PMID: 23576562 PMCID: PMC3687032.
ArhGAP15, a Rac-specific GTPase-activating protein, plays a dual role in inhibiting small GTPase signaling. Radu M, Rawat SJ, Beeser A, Iliuk A, Tao WA, et al. The Journal of biological chemistry. 2013; 288(29):21117-25. PubMed PMID:23760270 PMCID: PMC3774378.
The tumor suppressor Mst1 promotes changes in the cellular redox state by phosphorylation and inactivation of peroxiredoxin-1 protein. Rawat SJ, Creasy CL, Peterson JR, Chernoff J. The Journal of biological chemistry. 2013; 288(12):8762-71.PubMed PMID:23386615 PMCID:PMC3605693.
p21-Activated kinase 1 is required for efficient tumor formation and progression in a Ras-mediated skin cancer model. Chow HY, Jubb AM, Koch JN, Jaffer ZM, Stepanova D, et al. Cancer research. 2012; 72(22):5966-75. NIHMSID: NIHMS407835 PubMed PMID: 22983922 PMCID: PMC3500416.
Sumoylated protein tyrosine phosphatase 1B localizes to the inner nuclear membrane and regulates the tyrosine phosphorylation of emerin. Yip SC, Cotteret S, Chernoff J. Journal of cell science. 2012; 125(Pt 2):310-6. PubMed PMID: 22266903 PMCID: PMC3283870.
