The Ranoa lab aims to develop T cell receptor-based immunotherapy against solid tumors. Specifically, Ranoa’s lab intends to:
- define chimeric antigen receptor (CAR)-T cell-mediated mutual reprogramming of tumor and host immune cells in the tumor microenvironment using syngeneic murine tumor models;
- uncover a deep mechanistic understanding of the spatiotemporal and molecular factors that define pathways of resistance to CAR-T based therapies as well as determine the molecular mechanisms responsible for altering the functional states of host immune cells in the tumor; and
- engineer the next generation of CAR-T cells to be able to overcome immune suppression in solid tumors, improve its therapeutic efficacy both as a single agent and in combination with other treatment modalities, and reduce its adverse side effects.
Ranoa uses CAR-T cells directed against tumors that display dysregulated antigens on their surface as a model system, perform in vitro co-culture assays and set up in vivo tumor models using both immune-competent and immuno-deficient mice. Common techniques used in the lab include basic molecular biology assays (such as genetic engineering, DNA/RNA/protein purification, flow cytometry, ELISA-based assays, RT-qPCR), tissue culture work (such as handling human and murine tumor cell lines, primary T cell purification from human and murine tissues, lentiviral and retroviral transduction of activated T cells, co-culture assays of tumor and effector T cells), animal work (such as establishing murine tumor models, administering treatment through various routes, breeding mice, isolating tissue samples for downstream processes), and big data analyses (such as bulk RNA sequencing, single-cell RNA sequencing, spatial transcriptomics, data mining).