Jing Huang, Ph.D.
Laboratory of Cancer Biology and Genetics
Building 37, Room 3140A
Bethesda, MD 20892-4258
The research interest of the Cancer and Stem Cell Epigenetics Section focuses on studying the roles of p53 in stem cells. Specifically, we are investigating the roles of p53 downstream targets in the regulation of stem cell differentiation and apoptosis and how these roles are related to the developmental roles and tumor suppressive functions of p53. We have two complementary stem cell models: embryonic stem cells (ESCs) and mesenchymal stromal/stem cells (MSCs).
Project 1: Study p53-mediated DNA damage responses of ESCs. ESCs can develop into many different cell types and have huge potential in clinical application. However, it is under appreciated how ESCs maintain their genome stability responding to DNA damage insults. We aim to address this question by studying how p53 regulates the DNA damage responses of ESCs. We and others have found that p53 plays important roles in the regulation of ESC differentiation after DNA damage. To achieve this, p53 down-regulates the transcription of many ES cell critical genes (Li et al., Cell Stem Cell, 2015; Zhang et al., Cell Cycle, 2013; Li et al., Molecular Cell, 2012; Lee et al., PNAS, 2010). Since ESCs are derived from blastocysts, our study may also shed new light on the emerging developmental roles of p53.
Project 2: Investigate the roles of p53 in MSCs (also called bone marrow-derived MSCs or BMSCs) and osteosarcoma. MSCs are proposed to be one of the cells of origin of osteosarcoma. p53 plays important roles in suppressing osteosarcoma. However, the precise roles of p53 in MSCs and how these roles are related to the osteosarcoma suppressive function of p53 are unclear. We hope to use MSCs as a model system to gain new insights into the osteosarcoma suppressive functions of p53 (He et al., Stem Cells, 2015). Recently, we found that Runx2, a p53-repressed key transcription factor in bone development, is required for the survival of osteosarcoma cells (Shin et al., PLOS Genetics, 2016). We are currently exploring the possibility of translating this discovery into therapeutic strategies for osteosarcoma.
To achieve our goals, we use various classical and cutting-edge techniques including molecular biology (such as CRISPR), biochemistry (e.g., proteomics), mouse genetics, genomics (e.g., ChIP-seq and RNA-seq), and systems biology.
Our program has strong effort in training with a flexible combination of publication, seminar, and journal club opportunities. All of the five past postdoctoral trainees are continuing their scientific career: three are independent investigators with their own laboratories.
Dr. Huang received his BS in Biochemistry from Peking University. He studied the estrogen receptor signaling in breast cancer with Drs. Robert Bambara and Mesut Muyan at the University of Rochester (NY) and received his PhD in 2004. After his postdoctoral training in cancer epigenetics with Dr. Shelley Berger at the Wistar Institute, he joined the Laboratory of Cancer Biology and Genetics as a tenure-track Principal Investigator in 2008. Dr. Huang won a NCI Director's Innovation Award (co-recipient) in 2011. Dr. Huang received his tenure in 2016.
He Y, Zhu W, Shin MH, Gary J, Liu C, Dubois W, Hoover SB, Jiang S, Marrogi E, Mock B, Simpson RM, Huang J. cFOS-SOX9 Axis Reprograms Bone Marrow-Derived Mesenchymal Stem Cells into Chondroblastic Osteosarcoma. Stem Cell Reports. 2017;8(6):1630-1644.
Shin MH, He Y, Marrogi E, Piperdi S, Ren L, Khanna C, Gorlick R, Liu C, Huang J. A RUNX2-Mediated Epigenetic Regulation of the Survival of p53 Defective Cancer Cells. PLoS Genet. 2016;12(2):e1005884.
He Y, de Castro LF, Shin MH, Dubois W, Yang HH, Jiang S, Mishra PJ, Ren L, Gou H, Lal A, Khanna C, Merlino G, Lee M, Robey PG, Huang J. p53 loss increases the osteogenic differentiation of bone marrow stromal cells. Stem Cells. 2015;33(4):1304-19.
Li M, Gou H, Tripathi BK, Huang J, Jiang S, Dubois W, Waybright T, Lei M, Shi J, Zhou M, Huang J. An Apela RNA-Containing Negative Feedback Loop Regulates p53-Mediated Apoptosis in Embryonic Stem Cells. Cell Stem Cell. 2015;16(6):669-83.
Li M, He Y, Dubois W, Wu X, Shi J, Huang J. Distinct regulatory mechanisms and functions for p53-activated and p53-repressed DNA damage response genes in embryonic stem cells. Mol Cell. 2012;46(1):30-42.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on February 4th, 2019