Kyle G. Daniels, PhD

Dr. Daniels aims to improve the ability of engineered T cells to kill cancer. Specifically, his goal is to understand how signaling events during T cell activation determine the therapeutic properties of activated T cells. He uses synthetic immunology techniques and computational methods to search for synthetic receptors that confer desired functions upon T cells. Ultimately, he hopes to design and create receptors that improve the ability of T cells to proliferate, persist, recruit other immune cells, and kill cancer cells.

Julia C. Carnevale, MD

Pancreatic cancer may soon become the second leading cause of cancer deaths in the nation. While many cancers have mutations that can be targeted with specific drugs, historically no such targets had been recognized in pancreatic cancer. This changed recently with the discovery that approximately one of every four pancreatic cancers has a defect in the machinery that repairs DNA damage. For example, some have been found to have mutations in the BRCA genes as well as other similar genes involved in repairing double-strand breaks in DNA.

Jiaxi Wu, PhD

Dr. Wu is investigating the mechanism of dendritic cell (DC) missing-self recognition and migration. DCs recognize and present antigens to lymphocytes, a process that is essential for shaping host immune responses against infection and cancer. How DCs recognize altered self cells (such as cancer cells and pathogen-infected cells) remains poorly understood. These studies should significantly enhance our understanding of DC biology and eventually contribute to the development of new strategies to harness DC function for immunotherapy against cancer.

Duy P. Nguyen, PhD

Dr. Nguyen [Connie and Bob Lurie Fellow] is analyzing the bacterial enzyme Cas9, which has emerged to be a versatile tool to manipulate the genome. He aims to develop an efficient method for selective delivery to and activation of Cas9 in cancer cells. In addition, the proposed research will explore the possibility of genome manipulation to create genetic models for understanding the mechanistic role of programmed cell death.

Thomas M. Norman, PhD

Dr. Norman is investigating the role that “epigenetic” differences play in cancer cells’ ability to develop drug resistance. These epigenetic changes result in altered gene expression. He will use a new technique called CRISPRi to systematically tune the expression of different parts of the genome and measure their effect on drug resistance. He hopes that these studies will identify new avenues for reducing resistance and expand our knowledge of the role epigenetic factors play in leukemia and other cancers.

Andrew L. Wolfe, PhD

Dr. Wolfe studies KRAS, a cancer-promoting protein that is activated by mutations in most forms of cancer. Tumor cells can become “addicted” to the presence of overactive KRAS protein, such that they die when KRAS is suddenly removed. He will focus his research on an exciting new class of inhibitors that cause active KRAS to be rapidly degraded. He aims to explore the effects of depleting KRAS on cancer cells, understand the mechanism by which these novel KRAS inhibitor drugs cause the protein to be degraded, and optimize the efficacy of these drugs.

Qi Hu, PhD

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).

Erin F. Simonds, PhD

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.