Research

Research in the Li lab is roughly divided into the following three areas:

• Molecular mechanisms of tumor response to therapy and approaches to enhance treatment efficacy, with special emphasis on skin cancer such as melanoma and squamous cell carcinoma where current treatment outcomes are dismal.
• Stem cell 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.

Roles of cell death factors such as caspases and necroptotic factors in cancer immunotherapy.  We are interested in understanding how cell death factors such as apoptotic caspases and necrptotic factors regulate host immune system response to cancer cell after cytotoxic cancer therapy such radiation therapy or chemotherapy. We hope such therapy can potentially be combined with the newly adopted immune checkpoint therapy  for enhanced therapeutic efficacy.

Cartwright IM, Liu Xinjian, Zhou M, Li F,  and Li C-Y. Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis. eLife 2017;6:e26371 doi: 10.7554/eLife.26371  PMCID: PMC5550274

Liu X, Li F, Huang Q, Zhang Z, Zhou L, Deng Y, Zhou M, Fleenor DE, Wang H, Kastan MB, and Li C-Y. Self-inflicted DNA double-strand breaks sustain tumorigenicity and stemness of cancer cells. Cell Research 2017 June, 27: 764-783.    DOI:10.1038/cr.2017.41

Li F, Liu X, Sampson JH, Bigner DD, and Li C-Y. Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors. Cancer Research 2016 September 76: 175143-5150.  PMCID: PMC5082736

Liu X, Zhou M, Mei L, Ruan J, Hu Q, Peng J, Su H, Liao H, Liu S, Liu W, Wang H, Huang Q, Li F, and Li C-Y. Key roles of necroptotic factors in promoting tumor growth.  Oncotarget  2016 April  7 : 22219-22233.  PMCID: PMC5008357

Liu X, He Y, Li F, Huang Q, Kato TA, Hall RP, and Li C-Y. Caspase-3 promotes genetic instability and carcinogenesis. Molecular Cell  2015 April 9, 58: 284-296. PMCID:PMC4408780

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. Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells. Cell Res.  2012 Feb;22(2):321-32.  PMID: 22105488

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.  Caspase 3-mediated stimulate of tumor cell repopulation during cancer radiotherapy. Nat Med. 2011 Jul 3;17(7):860-6.  PMID: 21725296

Li W, Li F, Huang Q, Shen J, Wolf, F, He Y, Liu X, Li CY. Quantitative, noninvasive imaging of radiation-induced DNA double-strand breaks in vivo. Cancer Res. 2011 Jun 15;71(12):4130-7. PMID: 21527553

Li F, Huang Q, Chen J, Peng Y, Roop D, Bedford JS, Li CY. Apoptotic cells activate the “Phoenix Rising” pathway to promote wound healing and tissue regeneration. Sci Signal. 2010 Feb 23:3(110);ra13. PMID: 20179271

Li F, He Z, Shen J, Huang Q, Li W, Wolf F, Li CY. Apoptotic caspases regulate induction of iPSCs from human fibroblasts.  Cell Stem Cell. 2010 Oct 8;7(4):508-20. PMID: 20887956

Li W, Li F, Huang Q, Fredrick BA, Bao S, Li CY.  Noninvasive imaging and quantification of epidermal growth factor receptor kinase activation in vivo. Cancer Res. 2008 Jul 1;68(13):4990-7.  PMID: 18593895

Li F, Sonveax P, Rabbani P, Liu S, Yan B, Huang Q, Vujaskovic Z, Dewhrist MW, Li CY. Regulation of HIF-1α stability through S-nitrosylation. Mol Cell. 2007 Apr 13;26(1):63-74.  PMID: 17434127

Yan B, Wang H, Peng Y, Hu Y, Wang H, Zhang X, Chen Q, Bedford JS, Dewhirst MW, Li CY. A unique role of the DNA fragmentation factor in maintaining genomic stability. Proc Natl Acad Sci USA.  2006 Jan 31;103(5):1504-9. PMID: 16432220

Li, CY, Shan S, Huang Q, Braun RD, Lanzen J, Hu K, Lin P, Dewhirst MW. Initial stages of tumor cell-induced angiogenesis: evaluation via skin window chambers in rodent models . J Natl Cancer Inst. 2000 Jan 19;92(2):143-7.  PMID: 10639516 

Huang Q, Shan S, Braun RD, Lanzen J, Anyrthambatla G, Kong G, Borelli M, Corry P, Dewhirst MW, Li CY.  Noninvasive visualization of tumors in rodent dorsal skin window chambers. Nat Biotechnol.  1999 Oct;17:1033-35. PMID: 1054711