Xin-Hai Pei, M.D., Ph.D.
Assistant Professor of Surgery
Description of Research
Dr. Pei’s research is primarily focused on how cell cycle inhibitors control adult stem cells and tumorigenesis in multiple organs. He is very interested in how tumor suppressors (Brca1, Pten, Men1) and transcriptional factors (GATA3, Bmi1) that play important role in maintaining and regulating stem cell functions collaborate with INK4 family of CDK inhibitors to control proliferation and differentiation of adult stem cells. More specifically, his research is to use genetically engineered mice as a tool to determine how INK4 genes control adult and cancer stem cells in lung, brain, islet, and breast. One major project that he has been focusing on is to study the function of p16ink4a, p18ink4c, and p19ink4d in controlling mammary stem and progenitor cells and mammary tumor development.
Dr. Pei discovered that p18INK4c is a haploinsufficient tumor suppressor and that its function is wholly dependent of CDK4. He demonstrated that p18INK4c and Pten cooperate in tumor suppression by constraining a positive regulatory loop between cell growth and cell cycle control pathways. He showed that p18INK4c also collaborates with Men1 to suppress neuroendocrine organ tumors and lung tumors. Recently, he has been focusing more on mammary stem/progenitor cell and cancer development. He discovered that p18INK4c is a downstream target of GATA3, constrains luminal progenitor cell expansion, and suppresses luminal tumorigenesis in the mammary gland. He identified that germline mutation of Brca1 alters the fate of mammary luminal cells and causes luminal-to-basal mammary tumor transformation. In addition, he also generated mice lacking p19INK4d and CUL9/PARC, a p53-binding E3 ligase. He found that both p19INK4d and CUL9/PARC are tumor suppressor genes.
- Provided the first genetic evidence showing that, in mice, the function of an INK4 gene is wholly dependent on Cdk4.
- Discovered p18INK4c is a haploinsufficient tumor suppressor in mice, and cooperates with Pten and Men1 to suppress tumor development.
- Discovered p18INK4c is a downstream target of GATA3, constrains luminal progenitor cell expansion, and suppresses luminal tumorigenesis in the mammary gland.
- Discovered germline mutation of Brca1 alters the fate of mammary luminal cells and causes luminal-to-basal mammary tumor transformation.
- Discovered CUL9/PARC ubiquitin ligase is a tumor suppressor.
Selected Cancer-Related Publications
- Bai F, Smith MD, Chan HL, Pei XH. Germline mutation of Brca1 alters the fate of mammary luminal cells and causes luminal-to-basal mammary tumor transformation. Oncogene :,2012 Read more »
- Zeng Y, Kotake Y, Pei XH, Smith MD, Xiong Y. p53 Binds to and Is Required for the Repression of Arf Tumor Suppressor by HDAC and Polycomb. Cancer Res 71:2781-92,2011 Read more »
Collaborating in the Multidisciplinary Research Program(s):