A postdoctoral position is available in the laboratory of Dr. Stephen Gottschalk in the Department of Bone Marrow Transplant & Cell Therapy. Genetically modified T cells expressing chimeric antigen receptor (CAR T cells) have potent antitumor in patients with hematological malignancies. However, CAR T cells so far had limited antitumor activity in early phase clinical studies for patients with solid tumors. This lack of efficacy is most likely multifactorial including a limited array of targetable antigens, heterogenous antigen expression, and the immunosuppressive tumor microenvironment. In an effort to better model CAR T-cell therapy in preclinical model for solid tumors we have recently established an immune competent sarcoma model. In this model, we target the tumor associated antigen B7-H3, that is expressed on the cell surface of human and murine sarcoma cells. We have successfully generated murine B7-H3-CAR T cells and have shown that these cells have – albeit modest – antitumor activity, closely mimicking human disease. In the proposed project we now want to perform mechanistic studies and perform a ‘candidate gene screen’ as well as a CRISPR/Cas9 in vivo screen in close collaboration with the Chi Lab at St Jude to discover genes that improve or impede T cell function. One major focus of this project is to better understand how transferred cells interact with the tumor microenvironment, and resident immune cells. Ultimate goal of these studies is to translate these approaches into early Phase clinical testing.
Successful applicants will have a strong publication record, excellent communication skills, and a Ph.D. or equivalent degree in molecular biology, cell biology, genetics, genomics, immunology, or a related area. To succeed in this position, you will have a strong immunology and cell biology background, with an emphasis on cellular immunology, and genetic manipulation of murine cells. Applicants with experience in generating and evaluating murine immune cells, gene editing, and/or immune competent murine models are strongly encouraged to apply.
For more information contact Enolia Marr at postdoc@stjude.org.
