Michael Curran
Professor
The University of Texas MD Anderson Cancer Center
Department of Immunology
During my postdoctoral fellowship in the lab of Dr. James Allison, I was at the forefront of developing T cell checkpoint blockade immunotherapy, including being the first to describe the functional consequences and therapeutic potential of blockade of the CTLA-4 and PD-1 T cell co-inhibitory pathways (PNAS 2010). Also, I described how 4-1BB agonist antibody therapy polarizes both CD4 and CD8 T cells to a unique phenotype with unparalleled anti- tumor cytotoxicity (PLoS One 2011, J Exp Med 2013). My lab at The University of Texas MD Anderson Cancer Center (MDACC) focuses on understanding the origins of immune privilege and T cell suppression in the “coldest” tumors, prostate and pancreatic cancer and glioblastoma. Answering this question has led us into two areas of research: one focused on the heightened density and activity of suppressive myeloid stroma in these cancers, and the other centered on alterations in tumor metabolism, which create a hostile microenvironment for infiltrating immune effectors. In the latter work, we have described how tumor hypoxia (JCI 2018) and hypermetabolism (CIR 2020) act to support tumor immune privilege. This work led to a phase I clinical trial here at MDACC showing that the combination of hypoxia reduction and checkpoint blockade can effectively treat patients with advanced metastatic prostate, pancreatic and head and neck cancers (CCR 2021). In studying the myeloid stroma, we worked with internal drug development experts to create super-potent agonists of the Stimulator of Interferon Genes (STINGs) innate immune sensor and demonstrate their potential in reversing suppressive polarization of myeloid stroma in multiple “cold” cancers (CIR 2017, JITC 2021, CCR 2021). Current efforts focus on targeting additional innate pathways including tumor cell phagocytosis (Sci Immunol 2022) to reactive tumor myeloid stroma and enhance tumor antigen cross-presentation. Mentoring both pre- and post-doctoral students is a critical mission of our lab. All students in the lab receive one on one mentorship, guidance in developing independent scientific thought, instruction in experimental techniques, practice at presentation skills (lab, local, and national talks/posters), mentoring experience, opportunities for both individual and team science, and ethics and statistical integrity training. Graduate students and post-doctoral fellows in the lab have an excellent history of funding by fellowships including a prestigious F99/K00 NCI Predoctoral to Postdoctoral Fellow Transition Award, and of advancing as independent scientists. Both multiple former graduate students, as well as medical fellows are now successful independent faculty members both in the US and internationally.
Education & Training
Ph.D. - Stanford University Medical School - 2001