Damon Runyon News

Dr. Hu is focusing on developing small molecule inhibitors to regulate the activity of Gαs, a subunit of the stimulatory G protein, which is encoded by the GNAS gene. Activating mutations of GNAS have been revealed to contribute to progression and metastasis of several kinds of cancers. About 64% of these mutations result in a single variant called R201C, which keeps Gαs in a constitutively active state. His goal is to design and synthesize small molecules to specifically inhibit the abnormally activated Gαs (R201C).

Dr. Schonhoft [Merck Fellow] aims to understand how immune cells abnormally proliferate and secrete a pathogenic variety of antibody proteins that cause organ and tissue damage, most notably in the heart and kidneys, during diseases such as amyloidosis and within a subset of multiple myelomas. His research will explain why particular antibody molecules are toxic while others are completely benign. This information may be used to develop new diagnostic probes for the early detection of these molecules, which could greatly improve the effectiveness of current clinical treatments.

Dr. Yadlapalli [HHMI Fellow] aims to elucidate the neural and molecular mechanisms involved in the regulation of metabolism. Living organisms from insects to humans have evolved neural mechanisms involving circadian clocks to synchronize their physiology, metabolism and behavior with the external environment. Disruption of these clocks is associated with increased incidence of cancer, diabetes, and heart disease.

Dr. Stroud [HHMI Fellow] is examining the distinct role of MeCP2, a protein that binds methyl-CpG-DNA and regulates neuronal chromatin, which "packages" DNA. The proposed research has significant implications for causes and mechanisms of cancer, as dysregulation of DNA methylation and other chromatin modifications represent early oncogenic events in a wide range of human cancers.  His project may have particular relevance to cancers of the nervous system.

Dr. Miller [HHMI Fellow] is investigating how cells ensure the correct partitioning of genetic material during cell division. Errors in this process occur in nearly all tumor cells and are the leading cause of miscarriages and congenital birth defects in humans. He is using novel techniques to isolate and examine the physical binding properties of the molecules that mediate this process.

Dr. Lee [HHMI Fellow] studies how the cells and molecules of the immune system within the tumor microenvironment contribute to initiation, tumor progression, and responses to anti-cancer therapy. Of the immune components, cells called interleukin-17-secreting lymphocytes have pivotal pathogenic roles in multiple cancers. He aims to elucidate the regulatory mechanisms by which this pathogenicity is controlled. Ultimately, a better understanding of the pathways may suggest promising targets for therapeutic strategies aimed at reducing the risk of cancer.

Dr. Molaro studies how an ancient "evolutionary arms race" between Krab-Zinc-Finger genes (KZNFs) and DNA sequence elements called retrotransposons has shaped transcriptional networks of stem cells and pluripotency. Because many cancers dedifferentiate to a stem cell-like state, refined knowledge about how KZNFs act to finely modulate transcriptional control may prove essential for the development of new cancer drugs. 

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.

Dr. Cai is interested in whether the state of cellular “protein crowdedness” can be used to differentiate healthy normal cells from cancer cells. Having the ability to monitor protein crowding and protein-folding landscapes within cells could provide a valuable “readout” for changes in metabolism and the overall health or dysfunction of cells.

Dr. Simonds is investigating tumor-initiating cells in pediatric glioblastoma, a type of brain tumor. This rare subpopulation of cells has the unique capacity to re-establish the tumor after therapy, and is therefore a critical therapeutic target. He is using a technique called mass cytometry to determine how these cells respond to communication signals from their environment. The goal of this work is to identify drugs that specifically kill tumor-initiating cells by blocking the signaling networks that sustain their survival.