Dr. Pan Zheng’s laboratory is studying the signal transduction molecules in hematopoietic stem cells in different physiological aging and pathological conditions. One signal transduction pathway of keen interest is TSC-mTOR pathway. TSC is named after a pediatric genetic disease: Tuberous Sclerosis Complex. This is a disease affecting 1 in 6,000 newborns. The affected children will have non-malignant tumors in the brain, kidneys, heart, eyes and lungs. These children have mutations in either TSC1 gene or TSC2 gene. Children’s National Health System has a special clinic to treat children with this disease. The TSC-mTOR pathway consists of about 20 different molecules inside the cells that sensing the amino acids, glucose and other nutrients, and give signals to cells to start multiple cellular processes, including transcription, translation, autophagy, glucose and glycogen metabolism. The researchers in Dr. Zheng’s laboratory are trying to understand the role of each molecule in making new blood cells (hematopoiesis), new immune cells (thymopoiesis) and tumor formation. Bone marrow transplantation is the special tool to study the hematopoiesis. Our research work has found that TSC-mTOR pathway plays important roles in maintaining hematopoietic stem cell self-renewal ability and control the stem cell differentiation to different types of blood cells. We found that certain therapeutic reagents may rejuvenate aging hematopoietic process.
Dr. Zheng’s laboratory also works on tumor immunology. They are studying ways to activate our own immune system for better surveillance to prevent tumor formation.
Chen C, Liu Y, Liu R, Ikenoue T, Guan KL, Liu Y, Zheng P. 2008. TSC/mTOR maintains quiescence and functions of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species. J. Exp. Med. 205:2397-408.
Chen C, Liu Y, Liu Y, Zheng P. 2009. mTOR Regulation and Therapeutic Rejuvenation of Aging Hematopoietic Stem Cells. Science Signaling 2:ra75.
Zhou P, Fang XF, McNally BA, Yu P, Zhu MZ, Fu YX, Wang LZ, Liu Y, Zheng P. 2009. Targeting Lymphotoxin-mediated Negative Selection to Prevent Prostate Cancer in Mice with Genetic Predisposition. Proc Natl Acad Sci U S A. 106(40):17134-9.
Wu Q, Liu Y, Chen C, Ikenoue T, Qiao Y, Li CS, Li W, Guan KL, Liu Y, Zheng P. 2011. The tuberous sclerosis complex -mtor pathway maintains the quiescence and survival of naïve t cells. J Immunol 187(3):1106-12.
Tang F, Wu Q, Ikenoue T, Guan KL, Liu Y, Zheng P. 2012. A critical role for Rictor in T lymphopoiesis. J Immunol. 189(4):1850-7.
Wong C, Chen C, Wu Q, Liu Y, Zheng P. 2015. A critical role for the regulated wnt-myc pathway in naive T cell survival. J Immunol. 194(1):158-67.
Ye P, Liu Y, Chen C, Tang F, Wu Q, Wang X, Liu CG, Liu X, Liu R, Liu Y, Zheng P. 2015. An mTORC1-Mdm2-Drosha axis for miRNA biogenesis in response to glucose- and amino acid-deprivation. Mol Cell 19:708-20.