Sylvester Comprehensive Cancer Center

Xin-Hai Pei, M.D., Ph.D.

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 transcription factors (GATA3, Bmi1) regulate and collaborate with the INK4 family of CDK inhibitors to control cell proliferation, differentiation, and tumorigenesis. More specifically, his research uses genetically engineered mice as a tool to determine how INK4 genes control normal and cancerous mammary stem cells as well as endocrine tumorigenesis. He generated 5 strains of knockout mice and characterized more than 30 different mice mutants for various CDK inhibitors, tumors suppressors, and transcription factors. Dr. Pei discovered that p18Ink4c is a haploinsufficient tumor suppressor and that its function is wholly dependent on Cdk4. He demonstrated that p18Ink4c collaborates with Men1 to suppress neuroendocrine tumorigenesis. He also discovered that p19Ink4d controls pituitary anterior lobe cell proliferation and tumorigenesis, which is independent of Cdk4. He identified that p18Ink4c is a downstream target of GATA3, constrains luminal progenitor cell expansion, and suppresses luminal tumorigenesis in the mammary gland. He further discovered that germline mutation of Brca1 alters the fate of mammary luminal cells, and that Brca1 suppresses EMT and stem cell dedifferentiation during mammary and tumor development. In addition, he demonstrated that CUL9/PARC, a p53-binding E3 ligase, is a tumor suppressor gene, and that it ubiquitylates Survivin to maintain genome integrity.

Highlights

  • Discovered p18Ink4c is a haploinsufficient tumor suppressor, and cooperates with Men1 to suppress endocrine tumor development.
  • Discovered p18Ink4c is a downstream target of GATA3, constrains luminal progenitor cell expansion, and suppresses luminal tumorigenesis in the mammary gland.
  • Discovered p19Ink4d is a tumor suppressor and controls pituitary anterior lobe cell proliferation.
  • Discovered germline mutation of Brca1 alters the fate of mammary luminal cells, and that Brca1 suppresses EMT and stem cell dedifferentiation during mammary and tumor development.
  • Discovered CUL9/PARC ubiquitin ligase is a tumor suppressor and ubiquitylates surviving to maintain genome integrity.

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 »

Programs

Collaborating in the Multidisciplinary Research Program(s):

E-mail a Friend