University of Florida
Project Term: January 1, 2019 - September 30, 2024
Blood cancers such as leukemia, lymphoma and myeloma may be caused by abnormal regulation of genes that control normal cell growth and development. Genes that are normally active can be silenced and/or genes normally not present in a blood cell are abnormally activated. The result can be an uncontrolled signal for continued cell growth or survival. Our group studies the molecular basis of this gene deregulation using cells cultured in the laboratory, human specimens, and animal models.
We have assembled a group of physician-scientists and basic scientists to mount an attack on abnormal gene regulation in blood cancers. It is our aim to understand the fundamental basis for abnormal gene regulation in blood cancers and to develop strategies to reverse this process. In the coming 5 years we are focusing on a family of proteins that target so called enhancer sequences- sites in the genome that have a role in controlling gene expression. We have found that inactivation of these enhancer active sequences causes a growth advantage to blood cancer cells and this may be in part by blocking the human immune response against the tumor.
Project 1: Ari Melnick, Weill Cornell- Dr. Melnick studies a regulator called KMT2D which is one of the commonest genes mutated in lymphoma.
Project 2: C. David Allis, PhD (Rockefeller U) and Scott Lowe, PhD (Memorial Sloan Kettering). These scientists study a class of leukemia associated with the shuffling of the protein called MLL (Mixed lineage leukemia).
Project 3: Robert Roeder, PhD, Rockefeller U. Dr. Roeder found a critical role for KDM6A in the development of MLL-associated leukemia and will map the regions of the protein required for the KDM6A action.
Project 4: Jonathan D. Licht, MD- The U of Florida. Dr. Licht studies KMT2C/D and KDM6A tumor suppression in multiple myeloma.