This Fox Chase professor participates in the Undergraduate Summer Research Fellowship.
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Assistant Professor
We are just starting to grasp the complexity of human cancer. Different tumor types tend to harbor mutations in different genes but how tissue specific selective damaging and aging processes result in specific combinations of mutated genes and how these processes are influenced by cell diversity and functionality remain poorly explored. Our research program will focus on understanding how tissue and organ degeneration, regeneration defects, and decline in regenerative capacity affect the initiation of cancer. We will use the liver as the target organ as it has several important characteristics that will facilitate tackling the above barriers. The liver has high endogenous regenerative capacity after damage resulting from trauma, toxicity or infection. Development of liver cancer is tightly linked to chronic liver damage and regenerative responses. Additionally, the liver is very amenable to experimental manipulation, not only by genetic tools but also by using viruses or even naked DNA.
We are just starting to grasp the complexity of human cancer. Different tumor types tend to harbor mutations in different genes but how tissue specific selective damaging and aging processes result in specific combinations of mutated genes and how these processes are influenced by cell diversity and functionality remain poorly explored. Our research program will focus on understanding how tissue and organ degeneration, regeneration defects, and decline in regenerative capacity affect the initiation of cancer. We will use the liver as the target organ as it has several important characteristics that will facilitate tackling the above barriers. The liver has high endogenous regenerative capacity after damage resulting from trauma, toxicity or infection. Development of liver cancer is tightly linked to chronic liver damage and regenerative responses. Additionally, the liver is very amenable to experimental manipulation, not only by genetic tools but also by using viruses or even naked DNA.
One of our projects is investigating how the different oncogenic events interact during hepatocellular carcinoma (HCC) initiation. To date, mouse models of HCC do not accurately replicate the molecular development of human liver cancer, a problem that presents an obstacle to fully understand the complex mechanisms of human HCC and poses a limit to the development of novel therapeutic approaches. We are combining mouse genetics with the use of transposons to better replicate the initiation of HCC as it develops in humans, as well as the interactions between different oncogenic mutations.
We are also interested in cholangiocarcinoma (CCA), another form of liver cancer. CCA can be anatomically divided into three different subtypes: distal, perihilar, and intrahepatic. Distal and perihilar originate from the common bile duct, whereas intrahepatic originates from the intrahepatic bile duct cells. While these anatomical differences are understood, our lab is interested in the molecular features of each type of CCA, which have yet to be fully elucidated. We have developed an in vitro model using organoids derived from intrahepatic and common bile duct cells from mice harboring human CCA oncogenic mutations.
Another of our projects involves applying liver regeneration from mouse models to humans. Our recent identification of hybrid periportal hepatocytes (HybHP) have shown an important role in the regeneration of the damaged liver in mouse. These findings form the basis of our next goal, which is to translate these results from our mouse models into human cell therapy. To achieve this, we are applying single cell sequencing to human liver in order to characterize human hybrid hepatocytes.
Recently, we have also demonstrated for the first time that patient MHC-I genotypes directly influence the probability that their tumor will acquire a specific recurrent oncogenic mutation. This provided new evidence that immunoediting of oncogenic mutations occurs in humans. Our lab is now interested in understanding the links between HLA genotype and cancer susceptibility as a way to implement preventive strategies from MHC-I allele genotypes.
Dr. Font-Burgada on PubMed
This Fox Chase professor participates in the Undergraduate Summer Research Fellowship.
Learn more about Research Volunteering.
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