Dr. Pawel K. Mazur
The University of Texas MD Anderson Cancer Center
Department of Experimental Radiation Oncology
We are seeking strong candidates for three high-impact, cross-disciplinary research projects within the pancreatic and lung cancer research program (mdanderson.org/MazurLab). Current projects are supported by several multi-year grants focused on the development of novel targeted and immuno-therapeutics.
Project 1. Adoptive immunotherapy (CAR-T cell-based therapy)
The candidate will work on basic and translational tumor immunology with a focus on T cell biology and adoptive immunotherapy. The Mazur lab generated Chimeric Antigen Receptor (CAR) constructs with reactivity to targets expressed on pancreatic as well as multiple lung cancer models. The Postdoctoral Fellow will lead the research to identify critical factors that enhance CAR-T cells expansion, ability to kill cancer cells and to withstand immunosuppression as well as prevent exhaustion in the tumor microenvironment. The candidate will utilize advanced molecular biology techniques to create enhancements, including knock down or overexpression of transcription factors regulating memory and exhaustion, chemokine receptors regulating trafficking, and cytokines regulating the function of the CAR-T and other endogenous immune cells in the tumor. Generated “armored” CAR-T cells will be tested using pre-clinical immunocompetent, endogenous mouse cancer models and human tumor samples. Our pre-clinical research platform takes advantage Magnetic Resonance Imaging (MRI) for real time tumor monitoring and co-culture organoid tumor models using the IncuCyte® live cell analysis system established in the lab (Nature Medicine, 2013 and Nature Medicine, 2015).
Project 2. Biochemistry (novel and “orphan” enzymes substrates discovery)
The candidate will determine the functions and mechanisms of action of novel lysine methyltransferases in pancreas and lung tumorigenesis. Using CRISPR/Cas9 genetics screening we identified novel and “orphan” enzymes important in driving cancer progression and drug resistance. The Postdoctoral Fellow will utilize unique mouse strains that we have generated, cutting-edge proteomics, gene-editing and biochemical technologies, and the collaborative effort of our research groups (project performed in collaboration with Dr. Or Gozani’s Lab at Stanford University world class expert in proteomics and enzyme biology) to identify enzymatic activities and their function in cancer therapy (Nature, 2014 and Genes and Development 2016). If warranted the prospective Postdoctoral Fellow will work with our collaborators at the Institute for Applied Cancer Science (IACS) to generate inhibitors targeting the identified enzymes for therapeutic intervention and test the compound using our established pre-clinical platform (Nature Medicine, 2015).
Project 3. Genetics and pharmacogenomics (multiplex CRISPR/Cas9 animal models of cancer)
The candidate will integrate CRISPR/Cas9-mediated genome engineering with conventional genetically-engineered alleles in mouse models of human lung and pancreatic cancers to create a high-throughput experimental pipeline to interrogate wide spectrums of tumor genotypes. Quantitative assessment of genotype-specific tumor responses to a panel of targeted therapies will generate a pharmacogenomic map that will guide patient treatment. The project is based on our recently published method for in vivo CRIPSR-mediated somatic-engineering in mice developed in collaboration with Dr. Tyler Jacks’ Lab at MIT (Nature Medicine, 2015). This method enables new comprehensive ways to combine mouse models and next-generation sequencing approaches to identify the dynamic interplay between specific tumor genotypes and the response to therapy. The project takes advantage of the “mouse clinic” approach utilizing pre-clinical mouse models integrated with MRI T2 real time tumor monitoring, as well as PDX and organoid tumor models established in Mazur lab (Nature Medicine, 2015).