Jing Huang, Ph.D.
Dr. Huang is interested in studying the roles of p53 in the stress response of stem cells. His current research focuses on embryonic stem cells and mesenchymal stem cells, which are relevant to sarcomas. Dr. Huang hopes to gain insights from his studies that may contribute to p53-based therapy for both stem cell diseases and cancer. To achieve these goals, Dr. Huang’s laboratory employs biochemical, molecular, epigenetic, and genomic approaches as well as mouse models.
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.
Selected Key Publications
cFOS-SOX9 Axis Reprograms Bone Marrow-Derived Mesenchymal Stem Cells into Chondroblastic Osteosarcoma.Stem Cell Reports. 2017. [ Journal Article ]
An Apela RNA-Containing Negative Feedback Loop Regulates p53-Mediated Apoptosis in Embryonic Stem Cells.Cell Stem Cell. 16(6): 669-683, 2015. [ Journal Article ]
- Stem Cells. 33: Cell Press 1304-1319, 2015. [ Journal Article ]
- PLOS Genetics. 12(2): e1005884, 2016. [ Journal Article ]
Distinct regulatory mechanisms and functions of p53-activated and p53-repressed DNA damage response genes in embryonic stem cells.Mol Cell. 46: 30-42, 2012. [ Journal Article ]
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.
|Waseem Abdulmannan Alzamzami||Predoctoral Fellow (Graduate Student)|
|Shunlin Jiang M.D.||Research Biologist|
|Young-Im Kim Ph.D.||Postdoctoral Fellow (Visiting)|
|Navdeep Malik Ph.D.||Postdoctoral Fellow (Visiting)|
|Jian Xu Ph.D.||Postdoctoral Fellow (Visiting)|
|Hualong Yan Ph.D.||Postdoctoral Fellow (Visiting)|