Dr. Li is the Vice Chair for Research in the Dept. of Dermatology. Some of the areas that his laboratory conducts research on include:
•Tumor response to therapy, with special emphasis on skin cancer such as melanoma and squamous cell carcinoma where current treatment outcomes are dismal;
•Stem cell and regenerative medicine, we will conduct research to investigate novel mechanisms of stem cell biology so that knowledge gained can be translated into regenerative medicine;
•Mechanisms of carcinogenesis, with emphasis on skin cancers, so that better strategies could be devised to prevent and treat these cancers.
Within these broad areas we have different ongoing research projects. Examples of some of the research projects include:
Unconventional roles of caspases in tumor response to chemotherapy or radiotherapy. A recent area of our laboratory has been the relationship of cell death and repopulation in tumors undergoing radiation and chemotherapy. In our studies, we discovered that cell death is a key trigger for tumor cell repopulation in radiation and chemotherapy. Unexpectedly, caspase 3, which is an executioner in cell death, positively regulate paracrine signaling from dying cells to stimulate proliferation of surviving tumor cells. Furthermore, we found that higher levels of pretreat caspase 3 activation is correlated with worse outcome in head and neck and breast cancers. This is again quite unexpected and contrary to established paradigm. We are currently actively studying the relevance of this mechanism in other malignancies including melanoma. We believe such studies will not only yield promising novel treatments for cancer but also new biomarkers of diagnostic or prognostic values.
Positive roles of apoptosis in wound healing and tissue regeneration. Another area of our research is the relationship between apoptosis and wound healing/tissue regeneration. In our recent research we discovered that cellular apoptosis, in particular, apoptotic caspases 3&7, play key roles in promoting skin wound healing and tissue regeneration. We named this pathway the “Phoenix Rising” pathway for wound healing and tissue regeneration. We are actively studying this mechanism with the hope that knowledge gained could be used for regenerative medicine.
Molecular factors involved in stem cell biology regulation and trans-differentiation. Recently our lab started to investigate molecular mechanisms involved in the maintenance and self-renewal of stem cells. Our efforts led to the discovery that caspases 8&3 play critical roles in the induction of pluripotent stem cells from human fibroblasts. We are in the process of dissecting additional roles of caspases in embryonic stem cells.
Direct reprogramming of one differentiated cell type into another differentiated cell type. Recently, we have been able to directly reprogram human fibroblast cells into dopaminergic neurons, which have great potential in Parksinson’s Disease. We are actively pursuing similar studies to reprogram skin fibroblasts into various cells of interest, including other skin cells, through direct reprogramming.
Education and Training
- Chinese Academy of Sciences (China), B.S. 1987
- Harvard University , D.Sc. 1992
Selected Grants and Awards
- Targeting ATM to boost systemic effects of radiotherapy and immunotherapy
- Anti-PD1 in combination with an inhibitor of PCSK9 to increase MHC class I molecule expression on tumor cells as immunotherapy for NSCLC
- K63-Ubiquitin-mediated cell signal regulation in epidermis
- Targeting apoptotic caspases to enhance cancer radiotherapy
- Image-Guided Radiation Therapy System for Small Animals
- Necroptotic genes in cancer cellular response to radiation
- Organization and Function of Cellular Structure
- Pro-oncogenic roles of apoptotic caspases
- Duke University Program in Environmental Health
- Exploring BCL-XL addiction in pancreatic ductal adenocarcinoma
- Dissecting mechanism(s) by which ionizing radiation promotes clonal expansion of premalignant cells in the thymus
- The "Phoenix Rising" pathway of tumor repopulation during radiotherapy
- Mechanisms involved in HP802-mediated wound healing
- Molecular Mechanisms of Tumor Response to Cytotoxic Chemotherapy
- Cancer Biology Training Grant
- HIF Genes in Head and Neck Cancer Radiotherapy
- A mechanistic investigation of space radiation-induced carcinogensis
- Mechanisms of HZE Particle-Induced Genetic Instability/Carcinogenic Transformation
- Imaging Tumor Hypoxia in a Transgenic Mouse Model
- Molecular Characterization of the Role of SOD Genes in Mammalian Cellular Response: Low Dose Ionizing Radiation
- Hyperthermia-mediated gene therapy approach for cancer
- Cell Viability in Implantable Diffusion Chambers