Metastatic Colorectal Cancer: Clinical Trial Conversation
Jonathan M. Hernandez, M.D.
Dr. Jonathan Hernandez is a surgical oncologist and hepatopancreatobiliary surgeon. He specializes in the treatment of pancreatic tumors and tumors of the liver and bile ducts. Dr. Hernandez's research efforts focus on elucidating the mechanisms through which tumor cells coopt the microenvironment of distant organs to form life-threatening metastases. The goal of his research program is to provide patients undergoing resection of localized tumor(s) with novel adjunctive therapies to prevent recurrence of their disease at a later time. Dr. Hernandez is also Assistant Program Director of the Surgical Oncology Research Fellowship.
American Board of Surgery: General Surgery
American Board of Surgery: Complex General Surgical Oncology
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.
Selected Key Publications
- Nature. 527(7578): 329-35, 2015. [ Journal Article ]
- Nature Cell Biology. 17(6): 816-26, 2015. [ Journal Article ]
- Nature Cell Biology. 17(1): 81-94, 2015. [ Journal Article ]
Defining optimum treatment of patients with pancreatic adenocarcinoma using regret-based decision curve analysis.Annals of Surgery. 259(6): 1208-14, 2014. [ Journal Article ]
Survival after pancreaticoduodenectomy is not improved by extending resections to achieve negative margins.Annals of Surgery. 250(1): 76-80, 2009. [ Journal Article ]
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.
|Imani Alexander||Postbaccalaureate Fellow (CRTA)|
|Reed Ayabe, M.D.||Clinical Fellow|
|Maureen Connolly R.N.||Research Nurse Specialist|
|Heyci Fuentes||Patient Care Coordinator (Contr.)|
|Shreya Gupta M.D.||Clinical Fellow|
|Cathleen Hannah R.N.||Research Nurse (Contr.)|
|Stacy Joyce PA-C||Physician Assistant (Contr.)|
|Joanna Lamot||Administrative Assistant|
|James D. McDonald, M.D.||Clinical Fellow|
|Amynah Pradhan CRNP-F, MSN, RN||Nurse Practitioner (Contr.)|
|Alok Ranjan, Ph.D.||Postdoctoral Fellow (Visiting)|
|Kirsten Remmert, Ph.D.||Staff Scientist|
|Samantha Ruff, M.D.||Clinical Fellow|
|Yvonne Shutack||Clinical Research Associate II (Contr.)|
|Surajit Sinha, Ph.D.||Research Fellow|
|Michael M. Wach, M.D.||Clinical Fellow|
To read the full article, see the NIH Clinical Center newsletter (Spring 2019).
Commissioner David A. Wright of the U.S. Nuclear Regulatory Commission visits the Ex-Vivo Lab