Scholar Profile

Enfu Hui

Assistant Professor
Department of Cell and Developmental Biology
University of California, San Diego
9500 Gilman Dr
La Jolla, CA 92093
Voice: 858-246-0832
Personal Homepage
2018 Searle Scholar

Research Interests

Canceer Immunotherapy Targets

Ideally, tumor cells are recognized as foreign cells by immune cells, and killed, because tumor cells display proteins that can stimulate immune cells. However, many tumor cells have evolved to produce or upregulate membrane proteins (e.g., PD-L1) that blind T cells. These proteins trigger molecular brakes – a.k.a. checkpoint receptors such as PD-1 – on immune cells to inhibit their functions, thereby promoting tumor survival. Remarkably, drugs that block PD-1 or its ligand PD-L1 have proven to release the PD-1 brake from immune cells, and demonstrated remarkable clinical activities in a variety of human cancers. Still, durable response is limited to a small subset of cancer patients. Identification of reliable predictive biomarkers, and targeting other immune checkpoints, either alone or in combination with PD-1 inhibitors, hold the promise of expanding the therapy to more tumor types and a larger populations of patients. However, these efforts are slowed down by the lack of molecular understanding of immune checkpoints. The goal of my lab at UCSD is to fill this mechanistic gap.

To push the field towards an in-depth, quantitative understanding of immune checkpoints, my lab utilizes a combination of cell-free membrane reconstitution, time-resolved live cell microscopy and cutting-edge cell biology approaches. With these approaches, we recently discovered that PD-1 suppresses immune cell activity by "turning off" a key stimulatory receptor called CD28. Now, my lab will continue to elucidate the PD-1 signaling pathway by identification of novel regulators and targets of PD-1. In addition, we are investigating whether and how additional immune "checkpoints" operate in conjunction with PD-1 to block CD28 or other immune receptors. We will identify the triggering molecules that turn these systems on, and signal transducers these systems recruit to suppress the immune response. Our findings could lead to the development of novel biomarkers and drug targets of cancer immunotherapy.