Jonathan M. Hernandez, M.D.
Surgical Oncology Program
Building 10, Room 4-3740
Bethesda, MD 20892
Exvivo Human Tissue Model: Hernandez Lab Research Interests
Dr. Hernandez’s research program focuses on interrogating the molecular underpinnings of metastatic colonization in order to interrupt the process prior to its completion. This line of investigation corresponds with a critical need in biomedical research, as metastases are the cause of greater than 90% of cancer related deaths. For patients undergoing resection, identifying and targeting the mechanisms that support the survival and outgrowth of latent, disseminated tumor cells holds great promise for the prevention of tumor recurrence. The lab has utilized complex cDNA and CRISPR-Cas9 screens to identify genes that conspire to drive the outgrowth of disseminated tumor cells, which ostensibly appear to be involved in epigenetic reprogramming, compensatory metabolism, and extracellular matrix deposition and remodeling. Current efforts are focused on elucidation of mechanisms and signal transduction pathway involvement for the identified genes of interest, to unveil clinically translatable targets. The lab utilizes multi-photon intravital microscopy to mechanistically interrogate and visualize the dynamics of metastatic outgrowth, including the roles of supporting stromal and immune cells. Moreover, the lab has begun pioneering first-ever human tissue models by repurposing perfusion systems to sustain resected tumor-bearing liver and peritoneum for prolonged ex vivo animation. We envision these models will enable us to 1) perform additional screens and validation experiments in human tissue for the first time, 2) personalize investigation of the metastatic cascade by leveraging multi-photon imaging with an individual patient’s tumor cells, which will be dissociated, labelled, and subsequently injected into the perfusate to seed that patient’s metastatic target tissue, and 3) utilized tumor-bearing tissue as a platform for drug discovery and evaluation of novel drug-delivery combinations and platforms, which we think has the potential to transcend multiple disciplines in translational medicine to permit investigations and manipulations not previously possible.
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 50 peer-reviewed publications and has contributed book chapters in numerous authoritative surgical textbooks.
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.
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.
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.
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.
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.
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This page was last updated on April 30th, 2019