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 (GATA, Bmi1) that play an 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 of current focus is 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. He discovered that loss of p18INK4c led to expansion of stem/progenitor cell populations in lung and mammary. Recently, he has been focusing more on mammary stem/progenitor cell and cancer development. He generated and characterized two mouse mammary tumor models. One developed predominantly ER+ luminal tumors, and the other formed ER- basal-like tumors. Both mouse strains developed tumors at a near complete penetrance at a similar age, providing a unique system to study mammary tumors and screen therapeutic agents. In addition, He also generated mice lacking p19INK4d and CUL9/PARC, a p53-binding E3 ligase. He found that both p19INK4d and CUL9/PARC-deficient mice developed tumors in various organs.
Highlights
- 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
- Discovered p18INK4c and Pten cooperate in tumor suppression by constraining a positive regulatory loop between cell growth and cell cycle control pathways, and p18INK4c, but not p27, collaborates with Men1 to suppress neuroendocrine organ tumors
- Discovered loss of p18INK4c leads to expansion of stem/progenitor cell populations in lung and mammary
- Discovered p18INK4c is a downstream target of GATA3, constrains luminal progenitor cell expansion, and suppresses luminal tumorigenesis in the mammary gland
Selected Cancer-Related Publications
Programs
Collaborating in the Multidisciplinary Research Program(s):