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Joan Font-Burgada, PhD

Joan Font-Burgada, PhD
About

Assistant Professor

Research Program

Lab Overview

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.

Education and Training

Educational Background

  • PhD in Genetics, University of Barcelona, Barcelona, 2010 
  • MS in Genetics, University of Barcelona, Barcelona, 2004 
  • BS in Biology, University of Barcelona, Barcelona, 2000

Honors & Awards

  • 2001 Predoctoral fellowship from Spanish Ministry of Education
  • 2005 Predoctoral fellowship. Scientific Parc of Barcelona (PCB)
  • 2010 Summa cum laude distinction of Doctoral Thesis
  • 2012 California Institute for Regenerative Medicine Postdoctoral Training Grant
  • 2015 K99/R00 NIH Pathway to Independence award
  • 2015 Hertzberg-Schechter Prize for Stem Cell Research
  • 2018 IRB Barcelona Alumni of Excellence Award
  • 2020 W.W. Smith Charitable Trust Award
  • 2020 NIH Director’s New Innovator Award
Research Profile

Research Program

Lab Overview

Lab Description

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.

Lab Staff

Lauren Strathearn, PhD

Postdoctoral Associate

Room: P3123
215-728-5689

Nhi Dang, PhD

Postdoctoral Associate

Room: P3123
215-728-5689

Marcos García Teneche

Graduate Student

Room: P3123
215-728-5689

Charlie Hewett

Technical Staff

Room: P3123
215-728-5689
Publications

Selected Publications

Strathearn LS, Stepanov AI, Font-Burgada J. "Inflammation in Primary and Metastatic Liver Tumorigenesis-Under the Influence of Alcohol and High-Fat Diets".
Nutrients 2020 Mar 27;12(4). pii:E933. doi: 10.3390/nu12040933. PubMed

Beauchemin L, Slifker M, Rossell D, Font-Burgada J. "Characterizing MHC-I Genotype Predictive Power for Oncogenic Mutation Probability in Cancer Patients".
Methods Mol Biol. 2020;2131:185-198. doi: 10.1007/978-1-0716-0389-5_8. PubMed

Wong J, Garcia-Carbonell R, Zelic M, Ho SB, Boland BS, Yao SJ, Desai SA, Das S, Planell N, Harris PA, Font-Burgada J, Taniguchi K, Bertin J, Salas A, Pasparakis M, Gough PJ, Kelliher M, Karin M, Guma M. "RIPK1 Mediates TNF-Induced Intestinal Crypt Apoptosis During Chronic NF-KB Activation".
Cell Mol Gastroenterol Hepatol. 2020;9(2):295-312. doi: 10.1016/j.jcmgh.2019.10.002. Epub2019 Oct 10. PubMed

de Prisco, N, Stout E, Font-Burgada J. "Specific labeling and lineage tracing of periportal hepatocytes using two-step genetic recombination".
Methods Mol Biol. 2019;1905:59-70. doi: 10.1007/978-1-4939-8961-4_6. PubMed

Marty P R, Thompson WK, Salem RM, Font-Burgada J, Zanetii M, Carter, H. "Evolutionary pressure against MHC class II binding  cancer mutations."
Cell. 2018 Oct 4;175(2):416-428.e13. doi: 10.1016/j.cell.2018.08.048. Epub 2018 Sep 20. Erratum in: Cell. 2018 Dec 13;175(7):1991. PMID: 30245014. PubMed. Correction.

Dow M, Pyke RM, Tsui BY, Alexandrov LB, Nakagawa H, Taniguchi K, Seki E, Harismendy O, Shalapour S, Karin M#, Carter H#, Font-Burgada J#. “Intergrative genomic analysis of mouse and human hepatocellular carcinoma”. Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):E9879-E9888. doi:10.1073/pnas.1811029115. (# co-corresponding authors). PubMed

Marty R, de Prisco N, Carter H, Font-Burgada J. MHC-I genotype drives early immune selection of oncogenic mutations. Molecular and Cellular Oncology, 5(2), 2018. PubMed

Marty R, Kaabinejadian S, Rossell D, Slifker M, van der Haar J, Engin HB, de Prisco N, Ideker T, Hildebrand WH, Font-Burgada J#,*, Carter H*. “ MHC-I genotype restricts the oncogenic mutational landscape”.
Cell. 2017 Nov 30;171(6):1272-1283.e15. doi: 10.1016/j.cell.2017.09.050. (#corresponding author, *equally contributed). PMID: 29107334  Highlighted in Nature Reviews Immunology (2017; 17, 729), Nature Reviews Clinical Oncology (2018; 15, 5) and Cell (2017; 171(6):1252–1253). PubMed

Umemura A, He F, Taniguchi K, Nakagawa H, Yamachika S, Font-Burgada J, Zhong Z, Subramaniam S, Raghunandan S, Duran A, Linares JF, Reina-Campos M, Umemura S, Valasek MA, Seki E, Yamaguchi K, Koike K, Itoh Y, Diaz-Meco MT, Moscat J, Karin M. “p62, Upregulated during Preneoplasia, Induces Hepatocellular Carcinogenesis by Maintaining Survival of Stressed HCC-Initiating Cells”.
Cancer Cell. 2016 May 19; doi: 10.1016/j.ccell.2016.04.006. [Epub ahead of print]. PubMed

Font-Burgada J, Sun B, Karin M. “Obesity and cancer: The oil that feeds the flame”.
Cell Metabolism. 2016 Jan 12; 23(1):48–62. doi: 10.1016/j.cmet.2015.12.015. PubMed ... Expand

Additional Publications

Dr. Font-Burgada on PubMed

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