Research in the transplantation laboratory is focused on two main objectives:
(1) Developing and validating a biomarker panel which predicts the risk of severe complications and organ failure in transplanting livers from donors with non-alcoholic fatty liver disease (NAFLD)
(2) Phenotyping and characterizing circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) patients indicated for orthotopic liver transplantation (OLT) to predict tumor recurrence risk after transplantation.
For end-stage liver disease, OLT is the only treatment option. The disparity between the patients on the liver transplant waiting list and the number of available donor livers continues to grow each year. The obesity epidemic is further threatening the donor pool, causing an increase in the frequency of steatosis, lipid deposits inside the hepatocytes, which is a known risk factor for transplant complications.
Our research focuses on developing a biomarker panel which predicts safety and efficacy in transplanting moderately steatotic donor livers. Our goal is to maintain, and potentially expand, access to OLT by identifying steatotic livers with a low risk of transplant complications after ischemia/reperfusion (I/R) injury. With increasing rates of obesity and non-alcoholic fatty liver disease in our region, biomarkers which identify fatty livers at high and low risk of complications will be essential to maintain access to OLT. Our lab has identified biomarkers associated with lipid metabolic dysfunction and alarmin signaling which are specifically expressed in livers at high risk of failure following I/R injury. Using models of diet-induced fatty liver disease and donor liver biopsies, we are currently validating and applying our biomarker panel to identify livers at high risk for complications in OLT.
Hepatocellular carcinoma (HCC) is the 5th most common cancer worldwide and the rate of HCC is steadily increasing. HCC is highly resistant to chemotherapy, leaving OLT as the only potential curative therapy. However, the risk of HCC recurrence after OLT is high. HCC has an unpredictable pattern of recurrence, with some tumors recurring only in the transplanted liver. CTCs are the major source of HCC cells which remain in patients after OLT and their subsequent metastasis and reactivation represents the primary source of new tumor formation after OLT. Our goal is to identify CTC populations in HCC patients prior to OLT and, based on the characteristics of the CTC population and patients specific tumor characteristics, predict their risk of HCC recurrence prior to OLT. Understanding the CTC population and the tumor oncogene profile may assist doctors in developing a patient specific treatment strategy post-transplant to limit HCC recurrence and increase tumor-free survival rates.