The Kalbasi laboratory tackles questions at the intersection of immunology and cancer biology, with an emphasis on therapeutic development. Here are some selected areas of interest:
Cytokine-based rewiring of T cells: Advances in gene therapy and synthetic biology have ushered in a new era in T cell therapy. Engineered T cells can now be dynamically modulated to perform context-specific functions. To leverage these technologies, the lab is studying how external cytokine signals, especially common gamma chain family, shape T cell function (Kalbasi, et al. Nature 2022).
Unveiling sarcoma targets through cell-of-origin queries: Most patients with sarcoma have yet to benefit from immunotherapy, which may in part be related to the absence of natural endogenous T cell responses to sarcoma. Engineered T cell approaches offer a solution to this problem, but therapeutic T cell targets are critical. The lab is examining sarcoma cell-of-origin as an approach to unveil rational, lineage-based therapeutic targets for T cell therapy.
Myeloid reprogramming: Myeloid cells are prevalent in the sarcoma microenvironment and further recruited by radiation and other cytotoxic therapies. The laboratory is studying how activation of pattern recognition receptor signaling may serve to bias the fate of radiation-associated myeloid cells toward one that promotes anti-tumor functions of T cells.
Tumor-intrinsic resistance to radiotherapy: Cancer cells evolve under immunologic pressure and not surprisingly, find myriad ways to evade immune attack. Uncovering and bypassing these evasive tactics can restore the efficacy of immunotherapy (Kalbasi, et al. Sci Transl Med 2020). The lab is studying whether the same principles may apply to radiation resistance, which may be both immune-dependent or immune-independent.
Research Tools: The Kalbasi lab aims to leverage the growing toolkits developed by synthetic biologists to study perturbations of the immune system and cancer and identify new therapeutic approaches. This means we are heavily invested in syngeneic mouse model systems to faithfully capture tumor - immune interactions, including adoptive transfer models. The lab leverages molecular biology, viral and CRISPR based genetic engineering, basic and advanced immunologic assays, and next-generation sequencing, including single cell approaches. Our group includes both wet and dry lab scientists. We are excited and unafraid to try new techniques and/or engage more experienced collaborators. Finally, the lab has a strong translational focus with a disease interest in sarcoma and melanoma and therapeutic interests that include T cell therapy, immuno-oncology and radiation therapy. The lab is actively involved in biospecimen analysis related to clinical trials:
https://clinicaltrials.gov/ct2/show/NCT04119024?cond=il13ra2&draw=2&rank=1
https://clinicaltrials.gov/ct2/show/NCT04420975?cond=bo-112+sarcoma&draw=2&rank=1
https://clinicaltrials.gov/ct2/show/NCT02701153?cond=5-day+sarcoma+radiation&draw=2&rank=1