Daniel H. Goldman, PhD

Dr. Goldman studies the process of protein synthesis, which is often misregulated in cancer, causing uncontrolled cell growth and proliferation. The balance of protein production in healthy cells is maintained in part by RNA-binding proteins, which modulate the efficiency of mRNA translation by the ribosome. However, the mechanisms underlying such regulation are not well understood. He is combining high-throughput sequencing technologies with single-molecule imaging in living cells to elucidate the mechanisms by which RNA-binding proteins regulate protein synthesis.

Cara A. Rabik, MD, PhD

Dr. Rabik is examining how mutations in the WT1 gene result in methylation changes in acute myeloid leukemia (AML). WT1 recruits the machinery necessary for demethylation to its target genes, ultimately regulating gene expression. When WT1 is mutated, these genes remain methylated and inactive, preventing normal hematopoiesis. She is identifying WT1 target genes and mapping their methylation landscape both in leukemic and normal settings. She will also test drugs designed to cause demethylation to evaluate if these drugs can treat the leukemia caused by mutations in WT1.

Michael A. Koldobskiy, MD, PhD

Dr. Koldobskiy studies the ways that cancer cells rely on “epigenetic” modifications, or chemical marks that modify the expression of genes without a change in the genetic sequence itself. Variability of epigenetic marks allows cancer cells flexibility in turning genes on and off, and may account for resistance to treatment. By dissecting the mechanisms of epigenetic modification in pediatric acute lymphoblastic leukemia (ALL), the most common cancer in children, he aims to identify new targets for treatment.

Hanjing Peng, PhD

Dr. Peng seeks to identify compounds that inhibit the proteasome, the protein degradation machinery in the cell that maintains the balance of cell growth and death. Inhibitors that regulate proteasome function are potential anticancer drugs. Inspired by the functional mechanism of a class of natural products that includes FK506 and rapamycin, she has designed and constructed a synthetic library of compounds (macrocyclic "rapafucin") in search of potent proteasome inhibitors.

Stacy L. Cooper, MD

Dr. Cooper focuses on developing novel therapies for acute myeloid leukemia (AML), which has an approximately 50% mortality rate. Her work focuses on C/EBPalpha, a protein that is decreased in more than half of all AML patients. By determining how the production of this protein is regulated, she aims to understand the mechanisms for its reduction in leukemia and to develop strategies to target C/EBPalpha as a novel therapy for AML.