The human body craves balance. All of our biological systems work (or should work) in concert to keep us healthy. One imbalance can send ripple effects throughout the body, causing disease and sometimes death.
In my lab, we study a protein called Notch, which functions as a decision-maker. It’s vital to life. Too little of it, and we wouldn’t be born—but too much of it can lead to cancer.
One important role of Notch is in the development of the immune system. White blood cells come from stem cells, but at a certain point, they have a decision to make—whether to become B cells, T cells or bacteria-eating macrophages. Notch plays a similar role in the body, keeping the balance to help regulate other functions. But an excess of Notch can lead to cancer, including leukemia.
We are particularly interested in how Notch performs regulatory functions in normal development and in diseases. For example, we found that Notch breaks down other proteins to influence how cells divide and develop. They can direct cell lineage depending on which proteins they break down at what times and in what locations.
Only by studying the chain of events that leads from Notch to cancer can we hope to find a way to inhibit the dangerous effects of Notch without stopping its natural, healthy regulation.
Hematopoiesis is a developmental process where hematopoietic stem cells differentiate into different cell types through a series of lineage decisions, which are largely orchestrated by precise transcriptional programs. The basic helix-loop-helix family of transcriptional regulators includes E proteins encoded by the E2A, HEB and E2-2 genes and their inhibitors called Id proteins (Id1-4). Id proteins dimerize with E proteins and inhibit the DNA binding activity of E proteins. Therefore, the net E protein activity in a cell is determined by the concentration of both E and Id proteins. Work from our laboratory and others have shown that these proteins play important roles in several steps in hematopoiesis. E proteins are indispensable for the development of B and T lymphoid cells whereas Id proteins favor myeloid differentiation. These proteins have also been shown to be important for the maintenance of hematopoietic stem cells.
Recently, we have found that E proteins play crucial roles in suppressing the innate lymphoid fates while ensuring the robust production of B and T cells. Innate lymphoid cells are newly discovered classes of immune cells implicated in a variety of ailments such as asthma and inflammatory bowel diseases. We are interested in understanding how alternations in E protein function regulates the production of these cells, thus affecting the disease activities. The animal models we have collected over the years also offer us excellent opportunities to study the impact of these cells on immunity as well as tumor microenvironments.
Ph.D., Cornell University, Ithaca, New York, 1987
Honors and Awards
1989-1991 Cancer Research Institute Postdoctoral Fellowship
1992-1996 Cancer Research Institute Investigator Award
1994-1998 Irma T. Hirschl Trust Career Scientist Award
2002-2005 S. Graham Smith Distinguished Scientist Award
2014 J.Donald and Patricia H. Capra Award for Scientific Achievement
Reviewer for Immunity, Nature Genetics and Nature Immunology
Member of Scientific Advisory Committee of the Damon Runyon Cancer Research Foundation
Member of the NIH CMI-B study section
American Association for the Advancement of Science
American Association of Immunologists
Society of Chinese Bioscientists in America
Joined OMRF Scientific Staff in 1999.
He C, Medley SC, Kim J, Sun C, Kwon HR, Sakashita H, Pincu Y, Yao L, Eppard D, Dai B, Berry WL, Griffin TM, Olson LE. STAT1 modulates tissue wasting or overgrowth downstream from PDGFRβ. Genes Dev. 2017 Aug 15;31(16):1666-1678. doi: 10.1101/gad.300384.117. Epub 2017 Sep 18. PMID: 28924035
Molineros JE, Yang W, Zhou XJ, Sun C, Okada Y, Zhang H, Heng Chua K, Lau YL, Kochi Y, Suzuki A, Yamamoto K, Ma J, Bang SY, Lee HS, Kim K, Bae SC, Zhang H, Shen N, Looger LL, Nath SK. Confirmation of five novel susceptibility loci for systemic lupus erythematosus (SLE) and integrated network analysis of 82 SLE susceptibility loci. Hum Mol Genet. 2017 Mar 15;26(6):1205-1216. doi: 10.1093/hmg/ddx026. PMID: 28108556
Wang HC, Qian L, Zhao Y, Mengarelli J, Adrianto I, Montgomery CG, Urban JF Jr, Fung KM, Sun XH. Downregulation of E Protein Activity Augments an ILC2 Differentiation Program in the Thymus. J Immunol. 2017 Apr 15;198(8):3149-3156. Epub 2017 Mar 3. [Abstract]
Liu C, Wang HC, Yu S, Jin R, Tang H, Liu YF, Ge Q, Sun XH, Zhang Y. Id1 expression promotes T regulatory cell differentiation by facilitating TCR costimulation. J Immunol 193:663-672, 2014. [Abstract]
Zhao Y, Ling F, Wang HC, Sun XH. Chronic TLR Signaling Impairs the Long-Term Repopulating Potential of Hematopoietic Stem Cells of Wild Type but Not Id1 Deficient Mice. PLoS One 8:e55552, 2013. [Abstract]
Wang HC, Peng V, Zhao Y, Sun XH. Enhanced notch activation is advantageous but not essential for T cell lymphomagenesis in Id1 transgenic mice. PLoS One 7:e32944, 2012. [Abstract]
Wu W, Sun XH. A mechanism underlying NOTCH-induced and ubiquitin-mediated JAK3 degradation. J Biol Chem 286:41153-41162, 2011. [Abstract]
Nie L, Zhao Y, Wu W, Yang YZ, Wang HC, Sun XH. Notch-induced Asb2 expression promotes protein ubiquitination by forming non-canonical E3 ligase complexes. Cell Res 21:754-769, 2011. [Abstract]
Wang HC, Perry SS, Sun XH. Id1 attenuates Notch signaling and impairs T-cell commitment by elevating Deltex1 expression. Mol.Cell Biol. 29:4640-4652, 2009. [Abstract]
Immunobiology and Cancer Research Program, MS 29
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-7103
Fax: (405) 271-7128
News from the Sun lab
Scientists at the Oklahoma Medical Research Foundation have discovered a protein that acts as a gas pedal and brake for so-called “adult” stem cells. The findings, which appear in the current issue of the scientific journal Blood, could have important treatment implications for cancer and other life-threatening diseases. “This work has a great deal of […]
At its annual honors and awards banquet this evening, the Oklahoma Medical Research Foundation will name a pair of scientists as endowed chairs and add two new members to its board of directors. Xiao-Hong Sun, Ph.D., will be installed as the Eli Lilly Distinguished Chair in Biomedical Research, while Gary Gorbsky, Ph.D., will become the […]
In recognition of her highly regarded immunobiology and leukemia research, the Oklahoma Medical Research Foundation named OMRF investigator Dr. Xiao-Hong Sun its S. Graham Smith Distinguished Scientist at the OMRF Board of Directors biannual meeting Tuesday in Oklahoma City. Also Tuesday, two longtime OMRF board members were named life directors and two distinguished Oklahoma women […]