Jonathan M. Hernandez, M.D.


Surgical Oncology Program


Building 10, Room 4-3740
Bethesda, MD 20892


Research Topics

Translational Research

The ability to recapitulate the complexities of solid human tumors for the purposes of drug development and testing has been, and remains, a major obstacle in the progress of cancer care. Despite great efforts expended on pre-clinical optimization using existing validation models, most drugs simply fail to demonstrate efficacy when subjected to phase III clinical trial scrutiny. Our interpretation is that the currently available model systems lack the appropriate clinical predictive power. The reasons for the inadequacies of these model systems, which are largely based upon cell lines, mouse models or patient-derived xenografts, are myriad but are almost certainly related to the absence of the human stromal component and its intricate relationship with tumor cells. Indeed, modeling the multi-faceted interactions between human cancer cells and the multitude of various stromal components, including activated fibroblasts, immune cell infiltrate and the abnormal vasculature is, at present, an impossibility. We hypothesize that the advent of a system capable keeping intact human tumors viable in an ex vivo setting carries broad implications across many fields of investigational medicine and brings with it the potential to fundamentally alter the translational research landscape. Moreover, given that this system is based on a patient’s tumor, the benefits of personalized medicine could leap from generating lists of potentially useful drugs to designation of efficacious agents for that patient. The Hernandez lab has begun to satisfy the requirements of an ideal, translational human tumor system with the use of two innovative platforms and tumor straight from the operating room.


Dr. Hernandez graduated from medical school with honors from the University of Florida, and completed general surgery training at the University of South Florida. During his residency, Dr. Hernandez spent two years at the Moffitt Cancer Center and Research Institute interrogating molecular diagnostics for liver metastases and miRNA-mediated mechanisms of metastatic spread with the support of NIH funding. Following residency, Dr. Hernandez completed fellowship training in both surgical oncology and hepatopancreatobiliary surgery at Memorial Sloan Kettering Cancer Center. During his fellowships, Dr. Hernandez spent an additional two years in dedicated basic research studying metastatic colonization as a scholar in the Cell Biology Program of the Sloan Kettering Institute supported by NIH funding and a grant from America’s HepatoPancreatoBiliary Association. Dr. Hernandez was also a visiting investigator in the Cell and Developmental Biology Department of Weill Medical College of Cornell University studying metastatic niche evolution with funding support from the Conquer Cancer Foundation of the American Society of Clinical Oncology. Dr. Hernandez has authored over 100 peer-reviewed publications and has contributed book chapters in numerous authoritative surgical textbooks.

Selected Publications

  1. Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S, Singh S, Williams C, Soplop N, Uryu K, Pharmer L, King T, Bojmar L, Davies AE, Ararso Y, Zhang T, Zhang H, Hernandez J, Weiss JM, Dumont-Cole VD, Kramer K, Wexler LH, Narendran A, Schwartz GK, Healey JH, Sandstrom P, Labori KJ, Kure EH, Grandgenett PM, Hollingsworth MA, de Sousa M, Kaur S, Jain M, Mallya K, Batra SK, Jarnagin WR, Brady MS, Fodstad O, Muller V, Pantel K, Minn AJ, Bissell MJ, Garcia BA, Kang Y, Rajasekhar VK, Ghajar CM, Matei I, Peinado H, Bromberg J, Lyden D. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527(7578):329-35.
  2. Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK, Becker A, Hoshino A, Mark MT, Molina H, Xiang J, Zhang T, Theilen TM, García-Santos G, Williams C, Ararso Y, Huang Y, Rodrigues G, Shen TL, Labori KJ, Lothe IM, Kure EH, Hernandez J, Doussot A, Ebbesen SH, Grandgenett PM, Hollingsworth MA, Jain M, Mallya K, Batra SK, Jarnagin WR, Schwartz RE, Matei I, Peinado H, Stanger BZ, Bromberg J, Lyden D. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol. 2015;17(6):816-26.
  3. Okada T, Sinha S, Esposito I, Schiavon G, López-Lago MA, Su W, Pratilas CA, Abele C, Hernandez JM, Ohara M, Okada M, Viale A, Heguy A, Socci ND, Sapino A, Seshan VE, Long S, Inghirami G, Rosen N, Giancotti FG. The Rho GTPase Rnd1 suppresses mammary tumorigenesis and EMT by restraining Ras-MAPK signalling. Nat Cell Biol. 2015;17(1):81-94.
  4. Hernandez JM, Tsalatsanis A, Humphries LA, Miladinovic B, Djulbegovic B, Velanovich V. Defining optimum treatment of patients with pancreatic adenocarcinoma using regret-based decision curve analysis. Ann Surg. 2014;259(6):1208-14.
  5. Hernandez J, Mullinax J, Clark W, Toomey P, Villadolid D, Morton C, Ross S, Rosemurgy A. Survival after pancreaticoduodenectomy is not improved by extending resections to achieve negative margins. Ann Surg. 2009;250(1):76-80.

Related Scientific Focus Areas

This page was last updated on Friday, October 27, 2023