Jonathan M. Hernandez, M.D.

Jonathan M. Hernandez, M.D.

  • Center for Cancer Research
  • National Cancer Institute


Dr. Jonathan Hernandez is a surgical oncologist/HPB surgeon, chief of the surgical oncology section (Surgical Oncology Program/NCI/NIH), and an Associate Professor of Surgery (Uniformed Services University of the Health Sciences). He specializes in the treatment of metastatic and primary tumors of the liver, bile ducts and pancreas, as well as in the surgical management of complex abdominal tumors. Dr. Hernandez’s research efforts focus on implementation of ex-vivo human tumor systems that allow his lab to fully characterize tumors from the operating room and evaluate new therapies in an unfettered platform. The Hernandez lab utilizes these human tumor systems to 1) develop combination therapies for recalcitrant tumors, 2) delineate and target uncharacterized signaling axes for therapeutic gain in patients with cholangiocarcinoma, and 3) elucidate the mechanisms through which tumor cells coopt the microenvironment of distant organs to form life-threatening metastases.

Board Certifications
American Board of Surgery: General Surgery
American Board of Surgery: Complex General Surgical Oncology

Areas of Expertise

Information for Patients

Learn more about Dr. Hernandez's clinical research team and clinical trials.


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.



Selected Key Publications

Tumour exosome integrins determine organotropic metastasis

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
Nature. 527(7578): 329-35, 2015. [ Journal Article ]

Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver

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.
Nature Cell Biology. 17(6): 816-26, 2015. [ Journal Article ]

IBEX: A versatile multiplex optical imaging approach for deep phenotyping and spatial analysis of cells in complex tissues.

Radtke AJ, Kandov E, Lowekamp B, Speranza E, Chu CJ, Gola A, Thakur N, Shih R, Yao L, Yaniv ZR, Beuschel RT, Kabat J, Croteau J, Davis J, Hernandez JM, Germain RN
Proceedings of the National Academy of Sciences of the United States of America. 117(52): 55-65, 2020.
Full-Text Article
[ Journal Article ]

Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers.

Hoshino A, Kim HS, Bojmar L, Gyan KE, Cioffi M, Hernandez J, Zambirinis CP, Rodrigues G, Molina H, Heissel S, Mark MT, Steiner L, Benito-Martin A, Lucotti S, Di Giannatale A, Offer K, Nakajima M, Williams C, Nogués L, Pelissier Vatter FA, Hashimoto A, Davies AE, Freitas D, Kenific CM, Ararso Y, Buehring W, Lauritzen P, Ogitani Y, Sugiura K, Takahashi N, Alečković M, Bailey KA, Jolissant JS, Wang H, Harris A, Schaeffer LM, García-Santos G, Posner Z, Balachandran VP, Khakoo Y, Raju GP, Scherz A, Sagi I, Scherz-Shouval R, Yarden Y, Oren M, Malladi M, Petriccione M, De Braganca KC, Donzelli M, Fischer C, Vitolano S, Wright GP, Ganshaw L, Marrano M, Ahmed A, DeStefano J, Danzer E, Roehrl MHA, Lacayo NJ, Vincent TC, Weiser MR, Brady MS, Meyers PA, Wexler LH, Ambati SR, Chou AJ, Slotkin EK, Modak S, Roberts SS, Basu EM, Diolaiti D, Krantz BA, Cardoso F, Simpson AL, Berger M, Rudin CM, Simeone DM, Jain M, Ghajar CM, Batra SK, Stanger BZ, Bui J, Brown KA, Rajasekhar VK, Healey JH, de Sousa M, Kramer K, Sheth S, Baisch J, Pascual V, Heaton TE, La Quaglia MP, Pisapia DJ, Schwartz R, Zhang H, Liu Y, Shukla A, Blavier L, DeClerck YA, LaBarge M, Bissell MJ, Caffrey TC, Grandgenett PM, Hollingsworth MA, Bromberg J, Costa-Silva B, Peinado H, Kang Y, Garcia BA, O'Reilly EM, Kelsen D, Trippett TM, Jones DR, Matei IR, Jarnagin WR, Lyden D.
Cell. 182(4): 1044-1061, 2020.
Full-Text Article
[ Journal Article ]

Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer

Ma L, Hernandez MO, Zhao Y, Mehta M, Tran B, Kelly M, Rae Z, Hernandez JM, Davis JL, Martin SP, Kleiner DE, Hewitt SM, Ylaya K, Wood BJ, Greten TF, Wang XW
Cancer Cell. 36 (4): 418-430, 2019.
Full-Text Article
[ Journal Article ]

Job Vacancies

We have no open positions in our group at this time, please check back later.

To see all available positions at CCR, take a look at our Careers page. You can also subscribe to receive CCR's latest job and training opportunities in your inbox.


Cathleen Hannah
Research Nurse
Cathleen Hannah, R.N.
Kate Smith
Research Nurse
Kate Smith, R.N.
Rosie Melendez
Patient Care Coordinator
Rosie Miguel
Program Specialist
Joanna Lamot
Emily Smith
Emily C. Smith, Ph.D.
Yuri Lin
Postbaccalaureate Fellow
Yuri Lin
Ashley Rainey
Postbaccalaureate Fellow
Ashley Rainey
Postbaccalaureate Fellow
Hannah Stepp