Researches in my lab focus on helper T cell development and function. Regulatory T cells (Tregs) play an critical role in maintain immune homeostasis thus prevent autoimmunity and allergy. However, Tregs also contribute to tumor growth. FOXP3 is a key transcription factor critical for Treg development and function. While mouse Foxp3 encodes a single product containing all the coding exons (FOXP3 FL), human FOXP3 encodes two isoforms through RNA alternative splicing - a full length (FOXP3 FL) protein and the other lacking exon 2 (FOXP3 dE2). The in vivo functional differences between these two isoforms remain unclear. Our lab recently generated two mouse strains - one expressing only the FOXP3 dE2 isoform and the other expressing both isoforms through RNA alternative splicing as seen in humans- together with the WT mice that express to study how the two isoforms function in health and disease. Our recently published paper in Science Immunology showed that in both humans and mice, FOXP3 dE2 isoform alone failed to maintain immune homeostasis resulting autoimmunity. Surprisingly, we find that mice expressing only the FOXP3 dE2 isoform are highly resistant to triple negative breast cancer (TNBC) as well as other solid tumors. FOXP3 dE2 mRNA expression in TNBC patients strongly correlates with overall survival. Likewise the mice that co-express both isoforms (like in humans) are more resistant to TNBC compared with WT mice expressing only the FOXP3 FL isoform. We also designed a morpholino oligo that shift FOXP3 expression to the dE2 isoform with very high efficiency and collaborate with the researchers listed below to test the efficacy of the morpholino oligo in tumor immunotherapy.
Post-doctoral Fellowship - Benaroya Research Institute, Seattle, WA 2000-2005
Ph.D. - University of Washington, Seattle, WA 2000