Our laboratory is interested in understanding the cellular and molecular mechanisms of immune tolerance, antitumor immunity, and autoimmunity. Specifically, we focus on studying how microRNAs (miRNAs) and their target genes regulate immune tolerance, tumor immunology and autoimmune diseases. In addition, we are actively developing innovative genome engineering strategies for therapeutic purposes.
MicroRNAs have recently emerged as important factors in the post-transcriptional control of protein concentrations in metazoan organisms. For the past few years, we studied the functions of miRNAs in the mammalian immune system. We identified the first miRNA that regulates B cell tolerance and established its causative role in the development of lethal autoimmunity (Gonzalez-Martin et al, Nature Immunology, 2016 Apr;17:433-40). We also discovered critical roles for other microRNAs in different immune tolerance mechanisms and autoimmune diseases (Gonzalez-Martin and Lai et al, Nature Communications, 2016 Aug 2;7:12207, Ichiyama et al, Immunity, 2016 Jun 21;44:1284-98 and Liu et al, Journal of Experimental Medicine, Aug 22;213:1901-19). In addition, we developed the first B cell receptor reprogramming strategy using the latest genome editing technologies (Elife, 2019 Jan 17;8). Previously, work on tumor immunology established an important role for the chemokine receptor CCR5 in T cell antitumor responses (Gonzalez-Martin et al, Cancer Research, 2011 Aug 15;71:5455-66). Overall, our studies have established miRNAs as critical regulators of immune tolerance and autoimmunity, and revealed new mechanisms controlling antitumor immunity.
Current research in the lab continues to identify and study the roles of miRNAs and their target genes in immune tolerance, autoimmunity and tumor immunology by combining genetic, genomic, biochemical, and functional screen approaches to understand the functions and molecular mechanisms of miRNA control at molecular, cellular, and system levels. Specific lines of research include: (1) study the role of miRNAs and their target genes in B cell tolerance and autoimmune diseases, (2) identify novel cellular and molecular mechanisms of antitumor immunity, and (3) develop a new B cell editing technology. The mechanisms in identified might provide valuable biomarkers or therapeutic targets for the treatment of autoimmune diseases and for cancer immunotherapy.