Cancer Cell Biology
Area of interest
The ribosomal protein-Mdm2-p53 pathway and energy metabolism
The dynamic process of cell growth and division is under constant surveillance. As one of the primary “gatekeepers” of the cell, the p53 tumor suppressor plays a critical role in sensing a variety of stressors to maintain cellular homeostasis. Research in our laboratory focuses on delineating the biological function and molecular mechanism of p53. The broad goal of our lab is to uncover the complex regulatory network surrounding p53-signaling pathway, thereby providing a possible means to manipulate p53 function. Postdoctoral fellows and graduate students will receive supervision in a multi-disciplinary program based on (but not limited to) the research outlined below that seeks to maximize trainees’ abilities to successfully perform novel and speculative experiments. We are currently focusing on three related research areas.
- In vivo function of MDM2 E3 ubiquitin ligase in p53 regulation
The tumor suppressor p53 is a critical mediator of the cellular stress response, maintaining genomic integrity and preventing oncogenic transformation. MDM2, the primary negative regulator for p53, controls p53 through functioning as an E3 ubiquitin ligase targeting p53 for proteasomal degradation. Using mouse models expressing various knockout and knockin MDM2 mutants we define the function of MDM2 in p53 regulation, thereby providing insight into the MDM2-p53 regulatory mechanism and finding solutions to the current problems in the development of effective cancer therapeutics targeting the p53 pathway.
- The ribosomal protein-MDM2-p53 pathway in energy metabolism and cancer prevention
Cellular growth and division are two fundamental processes that are exquisitely sensitive and responsive to environmental fluctuations. One of the most energetically demanding functions of this process is ribosome biosynthesis, a key component for regulating overall protein synthesis and cell growth. Our studies have established the ribosomal protein-MDM2-p53 pathway that is critical in energy homeostasis. We are interested in delineating the function and mechanism of this pathway in oncogene-induced tumorigenesis and dietary-induced obesity and diabetes.
- Multifaceted mitochondrial p32 in the regulation of apoptotic cell death
Apoptosis is a tightly regulated form of programmed cell death that is critical for proper embryonic development, tissue homeostasis, and immune response. Aberrant regulation of this process contributes to autoimmune disorders, neurodegenerative disease and cancer. We have previously identified mitochondrial protein p32 as a critical mediator of p53’s apoptotic function. We are interested in characterizing the role of p32 in coordinating mitochondrial metabolism and apoptotic cell death, and exploring the potential of p32 as a therapeutic target for the treatment of cancers.
Awards and Honors
- 2010 The Battle Distinguished Cancer Research Award
- 2008 UNC Jefferson-Pilot Award
- 2008 American Cancer Society Scholar Award
- 2007 Leukemia & Lymphoma Society Scholar Award
- 2005 Junior Research Fellow, UNC Chapel Hill
- 2001 M. D. Anderson Research Trust Award
- 2000 Burroughs Wellcome Career Award in Biomedical Sciences
- 2000 Howard Temin Award