Ye Zheng

Research

The immune system is a powerful double-edged sword. On one hand, it is armed to fight a wide range of invading foreign pathogens. On the other hand, if left unchecked, it can also attack self-tissues and cause autoimmune diseases, such as type-1 diabetes, multiple sclerosis, and rheumatoid arthritis. There are multiple safeguard mechanisms built in our immune system to prevent autoimmune reaction. A subset of T cells, named regulatory T cells (Treg), play a key role in the maintenance of immune homeostasis.

Abnormal Treg function has been linked to a number of autoimmune diseases. Recent study showed that transcription factor Foxp3 is a pivotal regulator for Treg differentiation and function. Mutations of Foxp3 in human and mice lead to deficiency of regulatory T cells and fatal autoimmune disease. Zheng’s lab is interested in elucidating both the upstream pathways that turn on Foxp3 expression and the downstream genes that are regulated by Foxp3. Zheng and colleagues identified several DNA elements in Foxp3 locus that are conserved in several mammalian species. They are involved in the induction and maintenance of Foxp3 expression, and regulate the development and stability of regulatory T cell lineage. Using genomics approaches, Zheng and colleagues were able to map all Foxp3 downstream target genes. They showed that, among all Foxp3 targets, there is a small group of transcription factors that are implicated in Treg mediated suppression of different subtypes of autoimmune responses.

Zheng and his team are now further dissecting the Foxp3 transcriptional network in regulatory T cells and searching for key molecules involved in Treg suppression function. Since manipulations of Tregs can either attenuate or strengthen immune response, their findings can potentially open new avenues in treatment of autoimmune diseases, improvement of organ transplant survival, and enhancement of anti-tumor immunity.

Publications

  • Zheng Y*, Josefowicz SZ*, Chadhry A, Peng XP, Forbush K, Rudensky AY (2010). Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate. Nature 463:808-812. (*Equal Contribution)
  • Zheng Y, Chaudhry A, Kas A, deRoos P, Kim JM, Chu TT, Corcoran L, Treuting P, Klein U, Rudensky AY (2009). Regulatory T cell suppressor program co-opts transcription factor IRF4 to control Th2 responses. Nature 458:351-356.
  • Zheng Y, Rudensky AY (2007). Foxp3 in control of the regulatory T cell lineage. Nat. Immunol. 8:457-462.
  • Zheng Y, Josefowicz SZ, Kas A, Chu TT, Gavin MA, Rudensky AY (2007). Genome-wide analysis of Foxp3 target genes in developing and mature regulatory T cells. Nature 445:936-940.
  • Hsieh CS, Zheng Y, Liang Y, Fontenot JD, Rudensky AY (2006). An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat. Immunol. 7: 401-410.

Biography

Dr. Ye Zheng earned his B.S. degree in Biochemistry and Molecular Biology from Peking University in Beijing, China, and his Ph.D. degree in Biological Sciences from Columbia University in New York. He was awarded a postdoctoral fellowship sponsored by Cancer Research Institute to conduct research in Dr. Alexander Rudensky's lab at University of Washington in Seattle. After a brief sojourn as a research scholar at Memorial Sloan-Kettering Cancer Center, he joined the Salk Institute for Biological Studies as an assistant professor in 2009. He was named a Rita Allen Scholar in 2010.