Sloan-Kettering Institute // Immunology Program

Ming Li, PhD

The immune system has evolved to mount robust responses to pathogens while maintaining tolerance to self or innocuous antigens such as those found in commensal bacteria. Our general interest is to understand how this normal immunological function is ensured in health, and how it is dysregulated in disease, with an emphasis on the function and regulation of T lymphocytes.

T cells are important effectors and regulators of the immune system. A functional adaptive immune system is dependent on diverse and self-tolerant T cells, which are generated in the thymus, and are further maintained in peripheral lymphoid organs. Upon encountering antigens, T cells differentiate into various effector and regulatory subsets that play essential roles in immunity to pathogens, and tolerance to self tissues respectively.

Our recent studies have revealed TGF-beta/TGF-beta receptor and Akt/Foxo pathways as important regulators of thymic T cell development, and peripheral T cell homeostasis, tolerance, and immunity. A major current focus in the lab is to study how these evolutionarily ancient signaling modules are rewired to regulate highly specialized T cell activities, and to define their functions in autoimmune diseases, infectious diseases and cancer.

Publications

Ouyang W, Liao W, Luo CT, Yin N, Huse M, Kim MV, Peng M, Chan P, Ma Q, Mo Y, Meijer D, Zhao K, Rudensky AY, Atwal G, Zhang MQ, Li MO. Novel Foxo1-dependent transcriptional programs control T(reg) cell function. Nature. 2012 Nov 7;491(7425):554-9. doi: 10.1038/nature11581. Epub 2012 Nov 7.

Donkor MK, Sarkar A, Savage PA, Franklin RA, Johnson LK, Jungbluth AA, Allison JP, Li MO. Immunity. T cell surveillance of oncogene-induced prostate cancer is impeded by T cell-derived TGF-β1 cytokine. Immunity. 2011 Jul 22;35(1):123-34. doi: 10.1016/j.immuni.2011.04.019. Epub 2011 Jul 14.

Ouyang W, Beckett O, Ma Q, Li MO. Immunity. Transforming growth factor-beta signaling curbs thymic negative selection promoting regulatory T cell development. 2010 May 28;32(5):642-53. doi: 10.1016/j.immuni.2010.04.012. Epub 2010 May 13.

Ouyang W, Beckett O, Ma Q, Paik JH, DePinho RA, Li MO. Foxo proteins cooperatively control the differentiation of Foxp3+ regulatory T cells. Nat Immunol. 2010 Jul;11(7):618-27. doi: 10.1038/ni.1884. Epub 2010 May 13.

Ouyang W, Beckett O, Flavell RA, Li MO. Immunity. An essential role of the Forkhead-box transcription factor Foxo1 in control of T cell homeostasis and tolerance. Immunity. 2009 Mar 20;30(3):358-71. doi: 10.1016/j.immuni.2009.02.003. Epub 2009 Mar 12.