Kakareka - Hernandez - 2026

Prolonged Normothermic Ex Vivo Animation of Human and Porcine Tissue for Clinical Translation

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 models, most drugs simply fail to demonstrate efficacy when subjected to phase III clinical trial scrutiny. Our interpretation of this is that currently available model systems lack the appropriate clinical predictive power, particularly because they fail to include the aberrant vasculature, human stromal and immune components, and the intricate relationship with tumor cells. However, the potential exists for new models of human malignancy using intact tumors removed from patients, in which the complex spatial relationships between all cell types in the tumor microenvironment are perfectly preserved.

The lab has been optimizing our own ex vivo perfusion systems for use on tumor-bearing liver segments that are removed as part of standard treatment algorithms from patients at the NIH Clinical Center, as well as on smaller tumor biopsies from multiple disease sites. As a hepatobiliary oncologic surgeon, the lab has unparalleled access to tumor-bearing and paired non-tumor bearing human tissue immediately from the operating room. Our systems recapitulate much of the major human organ systems. For example, we have pumps and oxygenators that serve as our cardiovascular system and dialysis capability to serve as in-line kidneys. Because we have essentially “rebuilt” the human body around the tissue, the sustained tissue/tumor maintained ex-vivo mirror the complexities of a human tumor under near-physiologic conditions. Consequently, our system serves as an ideal model to study drug mechanisms. For example, real-time tumor responses to chemotherapeutic drugs delivered through the intact liver vasculature can be measured by serial biopsies taken over the course of drug delivery, which provides a window of insight into drug efficacy that would allow for the development of rational novel drug combinations. Moreover, perfusate is amenable to continuous sampling to facilitate biomarker discovery and tumor penetration is readily measured, which is an important feature considering that this has been nearly impossible to assess for patients in real time.

These human ex vivo perfusion systems come together at the intersection of physiology and cancer biology, creating an innovative platform for advancing patient care. The student will work with our multidisciplinary team consisting of surgeons, biomedical and electrical engineers, and hepatologists to utilize the systems to improve hepatic regional therapy. This will entail:

• Assist with procuring livers and bile ducts (human and porcine) and monitoring the perfusion machines during runs, including taking point of care labs, drug additions, serial biopsies, and blood samples.
• Optimization of organ positioning/suspension for uniform perfusion through the use of cutting-edge handheld ultrasound technology.
• Post-perfusion analysis of the liver tissue including H&E staining, Immunofluorescence, and transcriptomics.
• Post-perfusion analysis of bile duct tissue including H&E staining, Immunofluorescence, and transcriptomics. 

The BESIP student working in this area should have a background in biomedical engineering, human physiology, and cancer biology. As the system is controlled through custom code, computer programming experience with Python is preferred but not necessary. Working closely with the interdisciplinary team, the BESIP intern will gain valuable hands-on experience with multiple procedures and technologies and can expect to gain experience in various areas of cancer and biomedical research, most importantly those that are readily translatable to patients. This is a bedside-to-bench experience.