Rockefeller University, New York, NY

  • Developing Therapeutics for Fibrolamellar Hepatocellular Carcinoma
    2016 – 2017

    Principal Investigator: Sandy Simon, Ph.D., Professor
    Investigator Collaboration: Barbara A. Lyons, Ph.D., Professor, New Mexico State University

    The goal of this work is to develop a therapeutic for fibrolamellar hepatocellular carcinoma (FLHCC). These are three different two-year projects, with independent synergistic strategies, to identify small molecules to treat fibrolamellar. The strategy is based on this laboratory’s published work that there is a single alteration in the DNA that is found in all fibrolamellar tumors: a deletion of 400kB that results in a fusion gene, a chimera of the heat shock protein DNAJB1 and the catalytic subunit of protein kinase A, PRKACA and on this laboratory’s unpublished work that the chimera with an active kinase is sufficient to cause fibrolamellar.

    The first project is a high-throughput screen for molecules that directly block the chimera. This is an agnostic screen, which presumes no advanced knowledge about the chimera, with the goal of blocking its kinase activity. The screen will cover millions of compounds with no prior assumptions about what might work.

    The second project is a screen to identify the molecules that are directly phosphorylated by the chimera (in contrast to identifying downstream elements that change as a consequence of the activity of the chimera).

    The third project is an analysis of the structural dynamics of the chimera using a molecular dynamics simulation. This project is based on to-date-unpublished x-ray and NMR data on the structure of the chimera, together with molecular dynamics simulations, to identify sites on the chimera that would be appropriate for targeting therapeutics. Unlike the first project, which is an agnostic screen, this project is based on the hope that domains can be identified that are critical to the chimera’s.
  • Discovery of the chimera genetic mutation
    2014 – 2015

    FCF funding to Rockefeller University resulted in a potentially game-changing discovery of a unique genetic mutation common to all fibrolamellar tissues studied, a chimera. This research was conducted at the Tucker Davis Research Facility at Rockefeller University.  Dr. Sandy Simon is head of that facility and his daughter Elana, who is a fibrolamellar patient, was a lead researcher. The results were published in the preeminent medical journal, Science and reported in The Wall Street Journal, US News and World Report, AP, The Today Show, NBC Nightly News, and presented to President Obama.

    The Foundation granted Dr. Sandy Simon funds to study immunotherapy and fibrolamellar. Rockefeller University has put their full support behind Dr. Simon and charges no administrative fees for this research. Rockefeller University has provided Dr. Simon with a dedicated space exclusively for fibrolamellar research, The Tucker Davis Fibrolamellar Research Facility. FCF provided a freezer for fibrolamellar tissue samples. Dr. Simon’s goal is finding a cure – total eradication from the body. He feels this path is through the immune system using the patients’ own antibodies to track and kill the cancer cells. His research also includes melanoma and breast cancer cells.

    Dr. Simon has already discovered a way to extract antibodies from a patient, mark them, and re-introduce them into the body. The marked antibodies can attach to the smallest of cancer cells which will help surgeons and pathologists determine, during surgery, whether all the cancer has been removed.

Leave a Comment