Current Research

Revolutionizing cancer treatments

CAR T Cell Biology to inform the development of Next-generation CAR T cells

A central focus of the lab is to define how chimeric antigen receptors (CARs) signal within T cells and to understand the interface between the synthetic biology of CARs and the endogenous biology of T cells. By dissecting the molecular mechanisms of CAR signal transduction, we have uncovered key differences between CAR signaling and native T cell receptor (TCR) signaling that directly impact T cell function, fate decisions, exhaustion, and in vivo potency. These insights have enabled the rational design of next-generation CAR T cell therapies, including novel CAR architectures, adjunct and synergistic signaling modules, and logic-gated activation strategies. Collectively, this work has led to the development of innovative platforms such as ALA-CART, aimed at improving the durability and efficacy of CAR T cell therapy.

Development and Clinical Translation of CAR T Cell Therapy for Acute Myeloid Leukemia (AML)

A major goal of the lab is to bridge the gap between the remarkable success of CAR T cell therapy in B cell malignancies such as pre-B acute lymphoblastic leukemia, non-Hodgkin lymphoma, and multiple myeloma and its limited efficacy in myeloid leukemias, particularly acute myeloid leukemia (AML). Our work spans the preclinical development and testing of CAR T cells utilizing novel designs and targeting novel antigens, to working on clinical translation, clinical testing, and the development of guidelines on AML-directed CAR T cell therapy.

Development of CAR T Cell Therapies for Solid Tumors

While CAR T cell therapies have transformed the treatment of chemotherapy-refractory blood cancers, their success in solid tumors has been limited. Another major focus of the lab is the development of next-generation CAR T cells capable of overcoming the unique challenges posed by solid tumors. We are currently investigating the efficacy of novel CAR T cell designs in osteosarcoma (OS), using both preclinical models and comparative oncology approaches in canine (pet dog) patients with OS. This work aims to inform the development of first-in-children clinical trials for patients with treatment-refractory osteosarcoma and to extend these strategies to other hard-to-treat solid tumors.