Jing Huang, Ph.D.
- Center for Cancer Research
- National Cancer Institute
- Building 37, Room 3140A
- Bethesda, MD 20892-4258
Dr. Huang's research expertise lies in studying transcriptional and epigenetic regulation in both stem cells and cancer. His previous work as an independent investigator has been studying the role of p53 in embryonic stem cells and embryonic development. His current primary effort is identifying and targeting transcriptional and epigenetic vulnerabilities in osteosarcoma and breast cancer, aiming to develop new therapeutic strategies for these diseases. To achieve this goal, Dr. Huang's team focuses on several transcription factors (p53, CBFB, and RUNXs) and utilizes a variety of approaches, including molecular, biochemical, epigenetic, and genomic techniques, as well as mouse models and human samples.
Areas of Expertise
My research interest centers around understanding gene expression regulation in both stem cells and cancer cells. Specifically, my laboratory investigates the biological functions of transcription factors that play critical roles in both stem cell and cancer biology. To date, we have primarily focused on studying the tumor suppressor p53, also known as the guardian of the genome. However, we have recently expanded our research to include transcription factors (e.g., RUNXs, CBFB) that interact with p53. With extensive experience in embryonic stem cells (ESCs), mesenchymal stromal/stem cells (MSCs), and osteosarcoma (OS), we collaborate with intramural and extramural colleagues to study breast cancer. By conducting basic research on these transcription factors, we aim to generate novel insights into tumorigenesis and develop new methods of eliminating cancer cells.
Interest 1: Transcriptional and epigenetic stress responses of embryonic stem cells. As ESCs have the potential to differentiate into many different cell types and are a promising source for cell therapy, maintaining genomic stability and homeostasis is crucial for proper lineage choice. Despite this importance, the mechanisms by which ESCs maintain genome stability in response to DNA damage insults are poorly understood. To address this question, we have studied how the tumor suppressor protein p53 regulates the DNA damage responses of ESCs. Our research has shown that p53 plays an essential role in regulating ESC differentiation after DNA damage by down-regulating 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). Currently, we are studying the metabolic stress responses of ESCs. Recently, we found that Tfcp2l1-mediated fatty acid oxidation plays a critical role in maintaining ESC survival during metabolic stress (Yan et al., EMBO Reports, 2021). Our research may provide valuable insights into the mechanisms underlying human embryonic development and developmental disorders.
Interest 2: Transcriptional and epigenetic vulnerabilities in osteosarcoma. Osteosarcoma (OS) is the second leading cause of cancer-related death in children and young adults. Its standard care has not changed in the last four decades. Currently, there is no FDA-approved targeted therapy for OS. Immunotherapies are not effective for OS in clinical trials. Our overarching goal is to identify vulnerabilities in OS and contribute to developing new therapeutic strategies for this devastating cancer. Previously, we investigated osteosarcomagenesis using mesenchymal stromal/stem cells (MSCs) as a model. MSCs are thought to be one of the cells that contribute to the development of osteosarcoma. Although the role of p53 in osteosarcoma suppression is well-established, its roles in MSCs and how they relate to the osteosarcoma suppressive function of p53 are not yet fully understood. We and others showed that p53 represses osteoblastic differentiation of MSCs, and p53 loss in osteosarcoma cells correlates with the up-regulation of RUNX2, a master regulator of osteoblastic differentiation (He et al., Stem Cells, 2015). In addition, our team has found that human osteosarcoma cells depend on RUNX2 for survival, but MSCs are not (Shin et al., PLOS Genetics, 2016). These findings suggest that the RUNX2 signaling pathway may be an actionable vulnerability in osteosarcoma cells, and targeting CBFB, a transcription co-factor of RUNX2, may be a promising strategy. Indeed, Dr. John Bushweller's group (UVA) has already developed potent CBFB inhibitors, and we are collaborating with his group to test these inhibitors for osteosarcoma. In addition, we are searching for targets to enhance the efficacy of immunotherapy for OS. These studies will generate potentially actionable targets for OS.
Interest 3: Transcriptional and epigenetic vulnerabilities in breast cancer. The current effort focuses on cellular processes regulated by CBFB and RUNX1, which encode two subunits of a transcriptional complex. Recent genome-wide sequencing studies have shown that CBFB and RUNX1 are highly mutated in about 15% of human breast tumors, making it important to understand their functions in breast cancer. Our team has found that CBFB and its binding partner RUNX1 have a tumor-suppressive function in some subtypes of breast tumors by regulating the translation of hundreds of mRNAs (Malik et al., Nature Communications, 2019) and collaborating with the tumor suppressor p53 (Malik et al., PLoS Genetics, 2021). These exciting discoveries open new opportunities to search for vulnerabilities in breast cancer cells. Our recent studies suggest that CBFB regulates the metabolic homeostasis of breast cells by controlling mitochondrial translation. Based on this finding, we have identified autophagy inhibition as an approach to selectively killing breast cancer cells with CBFB mutations (Malik et al., Cancer Research, 2023). These findings contribute to designing novel strategies of precision medicine for breast cancer. We are currently developing 3D cultures from a newly developed mouse model of CBFB-deficient breast tumors to better understand the roles of CBFB in breast cancer.
Methods: We employ a wide range of established and innovative methods to advance our research objectives. Our toolbox includes traditional techniques such as molecular biology methods (e.g., PCR and cloning) and biochemistry techniques (e.g., Western blotting and proteomics). Additionally, we utilize cutting-edge methods such as CRISPR gene editing, advanced genomics techniques (such as ChIP-seq, RNA-seq, and single-cell genomics), mouse genetics, and systems biology approaches. We continuously evaluate and refine our methods, ensuring we have access to the latest technological advancements to tackle complex biological questions. By using these techniques, we aim to gain a deeper understanding of the molecular mechanisms underlying stem cell differentiation and cancer development, ultimately leading to the development of new therapeutic approaches.
Training: Training is a cornerstone of our program, and we offer our trainees a flexible combination of opportunities to develop their skills and knowledge. We provide regular seminars, journal club discussions, and opportunities to publish research findings in high-impact journals. Our goal is to provide a comprehensive training experience that prepares our trainees for successful careers in academia, industry, or government. Many of our past trainees have become independent investigators with their laboratories, and others have gone on to work as scientists in biotech and pharmaceutical companies. We are committed to supporting the success of our trainees and ensuring that they have the skills and knowledge they need to excel in their chosen careers.
Collaborators (former and current): Intramural: Drs. Glenn Merlino, Kent Hunter, Stuart Yuspa, Lalage Wakefield, Beverly Mock, Ji Luo, Mark Simpson, Rosie Kaplan, Daniel Larson, Pamela Robey, Chengyu Liu. Extramural: Drs. Shelley Berger, John Bushweller, Richard Gorlick
Dysregulation of mitochondrial translation caused by CBFB deficiency cooperates with mutant PIK3CA and is a vulnerability in breast cancer
CBFB cooperates with p53 to maintain TAp73 expression and suppress breast cancer
Fatty acid oxidation is required for embryonic stem cell survival during metabolic stress
The transcription factor CBFB suppresses breast cancer through orchestrating translation and transcription
An Apela RNA-Containing Negative Feedback Loop Regulates p53-Mediated Apoptosis in Embryonic Stem Cells
Jing Huang, Ph.D.
Dr. Huang holds a B.S. in Biochemistry from Peking University and a Ph.D. in 2004 from the University of Rochester, New York, where he studied estrogen receptor signaling in breast cancer under the guidance of Drs. Robert Bambara and Mesut Muyan. Following this, he completed his postdoctoral training in cancer epigenetics with Dr. Shelley Berger at the Wistar Institute. In 2008, he became a tenure-track Principal Investigator at the Laboratory of Cancer Biology and Genetics, where he received tenure in 2016. Dr. Huang is a recipient of several awards, including the NCI Director's Innovation Award (co-recipient), the NIH Stem Cell Center grant, and the Federal Technology Transfer Award.
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Congratulations to Hualong, who won an Outstanding Oral Presentation Award for his study of epigenetic regulation and therapeutic strategy of osteosarcoma!
Hualong and Young-Im are selected by the 2023 CCR-FYI Colloquium to give an oral presentation. Congratulations to both!
Payel joined the team. Welcome!
Hualong received a 2023 FARE award. Congratulations!
Young-Im received a 2022 FARE award. Congratulations!
Hualong won an Outstanding Oral Presentation Travel Award at 23rd CCR FYI Colloquium.
Young-Im Kim was selected to present her study of immunotherapy in osteosarcoma at the 23rd CCR FYI Colloquium.
Young-Im Birthday 2022
Navdeep's farewell lunch in 2022. She became a Principal Scientist in STRM.Bio in Boston.
Gamze's birthday celebration 2022
Hualong's birthday 2022