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Chuan-Yuan Li

Professor of Dermatology, Cancer Biology and Pharmacology
Clinical Sciences
(919) 613-8754
Research Interest: 
Cell cycle
Genetics
Signal transduction
Research Summary: 
Novel roles of caspases in regulating stemness, epigenetic cellular plasticity, and tumor response to radiation therapy and chemotherapy.
Research Description: 

Research in my lab is roughly divided into the following areas:
•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.

Publications: 
Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells.
Liu X, Li F, Stubblefield EA, Blanchard B, Richards TL, Larson GA, He Y, Huang Q, Tan AC, Zhang D, Benke TA, Sladek JR, Zahniser NR, Li CY.
Cell Res. 2012. 22:321-32.

Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy.
Huang Q, Li F, Liu X, Li W, Shi W, Liu FF, O'Sullivan B, He Z, Peng Y, Tan AC, Zhou L, Shen J, Han G, Wang XJ, Thorburn J, Thorburn A, Jimeno A, Raben D, Bedford JS, Li CY.
Nat Med. 2011. 17:860-6.

Apoptotic caspases regulate induction of iPSCs from human fibroblasts.
Li F, He Z, Shen J, Huang Q, Li W, Liu X, He Y, Wolf F, Li CY.
Cell Stem Cell. 2010. 7:508-20.

Apoptotic cells activate the "phoenix rising" pathway to promote wound healing and tissue regeneration.
Li F, Huang Q, Chen J, Peng Y, Roop DR, Bedford JS, Li CY.
Sci Signal. 2010. 3:ra13.

Regulation of HIF-1alpha stability through S-nitrosylation.
Li F, Sonveaux P, Rabbani ZN, Liu S, Yan B, Huang Q, Vujaskovic Z, Dewhirst MW, Li CY.
Mol Cell. 2007. 26:63-74.