Xu Lab

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Research Focus

We use molecular, cellular, genomics, proteomics and systems biology approaches to study the fundamental mechanisms that control the cellular response to DNA damaging agents. These regulatory events are central to two of the major issues in the field of cancer biology: 1) how and when cancers start and progress; and 2) what determines the sensitivity of tumors to therapeutic interventions. In terms of cancer causation, the critical role for the DNA damage response is demonstrated by the fact that a number of human cancer susceptibility syndromes are caused by inherited mutations affecting the DNA damage response. For example, inherited mutations in damage-response genes can lead to skin cancers (xeroderma pigmentosum genes), leukemia and lymphoma (ATM, NBS1 and Fanconi anemia genes), breast and ovarian cancers (p53, BRCA1, BRCA2), colon cancers (mismatch repair genes), and brain tumors (p53). The epidemiological observation that exposure to environmental DNA damaging agents contributes to at least 80 percent of all human cancers further illustrates the importance of these damage responses in cancer causation. On the other hand, since many cancer therapeutic interventions attempt to kill tumors by targeting the DNA, gene products involved in DNA damage-response pathways are also predictably critical for determining therapeutic outcomes. Thus, elucidation of the mechanisms involved in the DNA damage response has obvious importance both for understanding cancer causation and for eliciting cancer cures.

Major Research Programs

Project 1: The ATM pathway in DNA damage response and mitosis

Ataxia-Telangiectasia Mutated (ATM), mutated in the human autosomal recessive disorder Ataxia- Telangiectasia (A-T), is a PI-3 like kinase that functions as a sensor and signal transducer in the DNA damage response, and as such plays a critical role in maintaining genetic stability and preventing cancer formation. We study the complex signaling network mediated by the ATM kinase in the DNA damage response and mitosis. We have found that ATM is required for activation of the spindle checkpoint, a process that protects against chromosome mis-segregation by delaying sister chromatid separation. Our long-term goal of this project is to better understand the role of ATM in mitotic cell cycle control as a basis for providing insights into general mechanisms of genomic instability, carcinogenesis, cell growth and cell death.

 

Project 2: Novel approaches to molecular radiosensitization

Ionizing radiation (IR) is a key component of cancer therapy, and making tumor cells more sensitive to IR would improve therapeutic outcomes and long-term survival. We aim at targeting the DNA damage response pathway to sensitize tumor cells. For developing small molecules to interfere with the DNA damage response pathways, we apply high throughput screening, computational chemistry as well as medicinal chemistry in order to develop potent radiosensitizers.

For grant support and additional information see:

https://www.uab.edu/medicine/adda/

Bo Xu, M.D., Ph.D.

Distinguished Fellow and Chair, Oncology Department

Dr. Bo Xu serves as distinguished fellow and chair of oncology in Southern Research’s Oncology Department. In this role, he oversees cancer research and oncology drug discovery in the drug discovery division.  He is also the co-principal investigator of the NCI-designated Chemical Biology Consortium Comprehensive Center at SR. He is Professor of pathology and cell biology at the University of Alabama at Birmingham (UAB), a training faculty at the UAB Graduate Medical Sciences, and a member (senior scientist) at the NCI-designated Comprehensive Cancer Center at UAB. Continuously funded by the NIH and other federal/local/private organizations, Xu’s main research interests are mechanisms of the DNA damage response and cancer drug discovery.

[ Read Full Bio Here ]

Lab Members

Qinghua Zeng

Qinghua Zeng

Associate Research Biologist

Qinghua Zeng earned his M.D. in oral pathology at Norman Bethune University of Medical Science, China in 1988. He next became assistant professor and lecturer at the institution. In 1997, he earned his Ph.D. in biology at Northeast Normal University, China. While a Ph.D. student, he studied the role core histone acetylation in regulation of gene expression. He next spent one year as a postdoctoral fellow at Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gaterslaben, Germany, where he focused his study on differentiation of stem cells. He was also a postdoctoral fellow at the University of Michigan between 2001 and 2006. There, he studied cancer biology focused on cellular signaling. Subsequently, he became a research assistant professor at UAB in 2008. Zeng came to Southern Research in 2014 as associate research biologist in 2014, where he is currently working in the lab or Dr. Bo Xu. His main research interests are identification and characterization of signaling pathways that mediate cancer progression and metastasis. Since joining Dr. Xu’s lab, he has been actively working on projects related to DNA damage repair and anticancer drug discovery. His current project is focus on Porcupine (PORCN), a membrane-bound O-acyltransferase that is required for post-translational modification of all Wnts to enable their transport, secretion, and activity.

Joint Appointments

  • Member (Senior Scientist), UAB Comprehensive Cancer Center, UAB, Birmingham, AL
  • Adjunct Professor, Department of Pathology, UAB School of Medicine, UAB, Birmingham, AL


How To Work With Us

 

Southern Research welcomes collaboration opportunities with both academic and industrial research partners.