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Fang Li

Assistant Professor in Dermatology
Dermatology
Box 3135 Med Ctr, Durham, NC 27710
905 South LaSalle St, 3048 GSRB1, Durham, NC 27710

Selected Publications


SETDB1 Restrains Endogenous Retrovirus Expression and Antitumor Immunity during Radiotherapy.

Journal Article Cancer Res · August 3, 2022 UNLABELLED: The type I interferon response plays a pivotal role in promoting antitumor immune activity in response to radiotherapy. The identification of approaches to boost the radiation-induced type I interferon response could help improve the efficacy o ... Full text Link to item Cite

ATM inhibition enhances cancer immunotherapy by promoting mtDNA leakage and cGAS/STING activation.

Journal Article J Clin Invest · February 1, 2021 Novel approaches are needed to boost the efficacy of immune checkpoint blockade (ICB) therapy. Ataxia telangiectasia mutated (ATM) protein plays a central role in sensing DNA double-stranded breaks (DSBs) and coordinating their repair. Recent data indicate ... Full text Link to item Cite

Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer.

Journal Article Nature · December 2020 Despite its success in achieving the long-term survival of 10-30% of treated individuals, immune therapy is still ineffective for most patients with cancer1,2. Many efforts are therefore underway to identify new approaches that enhance such immune 'checkpo ... Full text Link to item Cite

ATM Paradoxically Promotes Oncogenic Transformation via Transcriptional Reprogramming.

Journal Article Cancer Res · April 15, 2020 The role of the ataxia-telangiectasia-mutated (ATM) gene in human malignancies, especially in solid tumors, remains poorly understood. In the present study, we explored the involvement of ATM in transforming primary human cells into cancer stem cells. We s ... Full text Link to item Cite

Endogenous Retrovirus Activation as a Key Mechanism of Anti-Tumor Immune Response in Radiotherapy.

Journal Article Radiat Res · April 2020 The generation of DNA double-strand breaks has historically been taught as the mechanism through which radiotherapy kills cancer cells. Recently, radiation-induced cytosolic DNA release and activation of the cGAS/STING pathway, with ensuing induction of in ... Full text Link to item Cite

Limited MOMP, ATM, and their roles in carcinogenesis and cancer treatment.

Journal Article Cell Biosci · 2020 Limited mitochondria outer membrane permeability (MOMP) is a novel biological process where mammalian cells initiate the intrinsic apoptosis pathway with increased mitochondrial permeability but survive. One of the major consequences of limited MOMP is apo ... Full text Link to item Cite

Non-apoptotic Roles of Caspases in Stem Cell Biology, Carcinogenesis, and Radiotherapy

Journal Article Current Stem Cell Reports · March 15, 2019 Purpose of Review: To summarize recent findings on novel roles of caspases in stem cell biology, tumor repopulation, and tissue regeneration. Contrary to the long-held notion that apoptotic caspases are exclusively executioners of programmed cell death, an ... Full text Cite

Novel roles of apoptotic caspases in tumor repopulation, epigenetic reprogramming, carcinogenesis, and beyond.

Journal Article Cancer Metastasis Rev · September 2018 Apoptotic caspases have long been studied for their roles in programmed cell death and tumor suppression. With recent discoveries, however, it is becoming apparent these cell death executioners are involved in additional biological pathways beyond killing ... Full text Link to item Cite

Caspase-3 regulates the migration, invasion and metastasis of colon cancer cells.

Journal Article Int J Cancer · August 15, 2018 Caspase-3 (CASP3) is a major mediator of apoptosis activated during cellular exposure to cytotoxic drugs, radiotherapy or immunotherapy. It is often used as a marker for efficacy of cancer therapy. However, recent reports indicate that caspase-3 has also n ... Full text Link to item Cite

Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis.

Journal Article Elife · July 10, 2017 The mechanism for Myc-induced genetic instability is not well understood. Here we show that sublethal activation of Caspase-3 plays an essential, facilitative role in Myc-induced genomic instability and oncogenic transformation. Overexpression of Myc resul ... Full text Link to item Cite

Self-inflicted DNA double-strand breaks sustain tumorigenicity and stemness of cancer cells.

Journal Article Cell Res · June 2017 DNA double-strand breaks (DSBs) are traditionally associated with cancer through their abilities to cause chromosomal instabilities or gene mutations. Here we report a new class of self-inflicted DNA DSBs that can drive tumor growth irrespective of their e ... Full text Link to item Cite

Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors.

Journal Article Cancer Res · September 1, 2016 Cancer stem-like cells (CSC) are thought to drive brain cancer, but their cellular and molecular origins remain uncertain. Here, we report the successful generation of induced CSC (iCSC) from primary human astrocytes through the expression of defined genet ... Full text Link to item Cite

Redefining the roles of apoptotic factors in carcinogenesis.

Journal Article Mol Cell Oncol · May 2016 In a recent study we reported that mammalian cells exposed to stress such as ionizing radiation can survive with activation of caspase-3 or caspase-7. We found that sublethal activation of the executioner caspases promotes chemical- and radiation-induced g ... Full text Link to item Cite

Key roles of necroptotic factors in promoting tumor growth.

Journal Article Oncotarget · April 19, 2016 Necroptotic factors are generally assumed to play a positive role in tumor therapy by eliminating damaged tumor cells. Here we show that, contrary to expectation, necroptotic factors RIPK1, RIPK3, and MLKL promote tumor growth. We demonstrate that genetic ... Full text Link to item Cite

Caspase-3 promotes genetic instability and carcinogenesis.

Journal Article Mol Cell · April 16, 2015 Apoptosis is typically considered an anti-oncogenic process since caspase activation can promote the elimination of genetically unstable or damaged cells. We report that a central effector of apoptosis, caspase-3, facilitates rather than suppresses chemica ... Full text Link to item Cite

Enhancing the efficiency of direct reprogramming of human primary fibroblasts into dopaminergic neuron-like cells through p53 suppression.

Journal Article Sci China Life Sci · September 2014 Dopaminergic (DA) neuron-like cells obtained through direct reprogramming of primary human fibroblasts offer exciting opportunities for treatment of Parkinson's disease. A significant obstacle is the low efficiency of conversion during the reprogramming pr ... Full text Link to item Cite

Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy.

Journal Article J Invest Dermatol · June 2014 Metastatic melanoma often relapses despite cytotoxic treatment, and hence the understanding of melanoma tumor repopulation is crucial for improving our current therapies. In this study, we aim to define the role of caspase 3 in melanoma tumor growth after ... Full text Link to item Cite

Caspase 3 promotes surviving melanoma tumor cell growth after cytotoxic therapy

Journal Article Journal of Investigative Dermatology · January 1, 2014 Metastatic melanoma often relapses despite cytotoxic treatment, and hence the understanding of melanoma tumor repopulation is crucial for improving our current therapies. In this study, we aim to define the role of caspase 3 in melanoma tumor growth after ... Full text Cite

Molecular mechanisms involved in tumor repopulation after radiotherapy.

Journal Article Transl Cancer Res · October 1, 2013 Radiotherapy remains one of most important treatment modalities for solid tumors. Current radiotherapy is mostly based on a set of concepts called the 4"R"s, which were established when there was lack of understanding of the underlying molecular mechanisms ... Full text Link to item Cite

Cell death-stimulated cell proliferation: a tissue regeneration mechanism usurped by tumors during radiotherapy.

Journal Article Semin Radiat Oncol · October 2013 The death of all the cancer cells in a tumor is the ultimate goal of cancer therapy. Therefore, much of the current effort in cancer research is focused on activating cellular machinery that facilitates cell death such as factors involved in causing apopto ... Full text Link to item Cite

Therapeutic targeting of erbB3 with MM-121/SAR256212 enhances antitumor activity of paclitaxel against erbB2-overexpressing breast cancer.

Journal Article Breast Cancer Res · 2013 INTRODUCTION: Elevated expression of erbB3 rendered erbB2-overexpressing breast cancer cells resistant to paclitaxel via PI-3 K/Akt-dependent upregulation of Survivin. It is unclear whether an erbB3-targeted therapy may abrogate erbB2-mediated paclitaxel r ... Full text Link to item Cite

Oncolytic virus-mediated tumor radiosensitization in mice through DNA-PKcs-specific shRNA.

Journal Article Translational cancer research · June 2012 One of the key issues in cancer radiotherapy research is to sensitize tumor cells to the cell killing effects of ionizing radiation while leaving normal tissues intact. One potential approach to achieve this is through tumor-specific targeting of DNA repai ... Full text Cite

Imaging molecular pathways: reporter genes.

Journal Article Radiat Res · April 2012 Molecular imaging is a rapidly advancing field that allows cancer biologists to look deeper into the complex inner workings of tumor cells, or whole tumors, in a non-invasive manner. In this review, we will summarize some recent advances that enable invest ... Full text Link to item Cite

Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells.

Journal Article Cell Res · February 2012 Transplantation of exogenous dopaminergic neuron (DA neurons) is a promising approach for treating Parkinson's disease (PD). However, a major stumbling block has been the lack of a reliable source of donor DA neurons. Here we show that a combination of fiv ... Full text Link to item Cite

Targeted entry via somatostatin receptors using a novel modified retrovirus glycoprotein that delivers genes at levels comparable to those of wild-type viral glycoproteins.

Journal Article J Virol · January 2012 Here we report a novel viral glycoprotein created by replacing a natural receptor-binding sequence of the ecotropic Moloney murine leukemia virus envelope glycoprotein with the peptide ligand somatostatin. This new chimeric glycoprotein, which has been nam ... Full text Link to item Cite

Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy.

Journal Article Nat Med · July 3, 2011 In cancer treatment, apoptosis is a well-recognized cell death mechanism through which cytotoxic agents kill tumor cells. Here we report that dying tumor cells use the apoptotic process to generate potent growth-stimulating signals to stimulate the repopul ... Full text Link to item Cite

Quantitative, noninvasive imaging of radiation-induced DNA double-strand breaks in vivo.

Journal Article Cancer Res · June 15, 2011 DNA double-strand breaks (DSB) are a major form of DNA damage and a key mechanism through which radiotherapy and some chemotherapeutic agents kill cancer cells. Despite its importance, measuring DNA DSBs is still a tedious task that is normally carried out ... Full text Link to item Cite

Non-invasive, quantitative monitoring of hyperthermia-induced EGFR activation in xenograft tumours.

Journal Article Int J Hyperthermia · 2011 PURPOSE: To examine the molecular mechanism of cellular EGFR activation during hyperthermia treatment. MATERIALS AND METHODS: EGR activities in tumour cells were quantified through the use of a recently developed split-luciferase-based EGFR reporter system ... Full text Link to item Cite

Novel luciferase-based reporter system to monitor activation of ErbB2/Her2/neu pathway noninvasively during radiotherapy.

Journal Article Int J Radiat Oncol Biol Phys · January 1, 2011 PURPOSE: To develop a split-luciferase-based reporter system that allows for noninvasive monitoring of activation of the Her2/neu pathway in vivo in a quantitative and sensitive manner. METHODS AND MATERIALS: Fusion proteins of the ErbB2/Her2/neu receptor ... Full text Link to item Cite

Apoptotic caspases regulate induction of iPSCs from human fibroblasts.

Journal Article Cell Stem Cell · October 8, 2010 The molecular mechanisms involved in the derivation of induced pluripotent stem cells (iPSCs) from differentiated cells are poorly understood. Here we report that caspases 3 and 8, two proteases associated with apoptotic cell death, play critical roles in ... Full text Link to item Cite

Apoptotic cells activate the "phoenix rising" pathway to promote wound healing and tissue regeneration.

Journal Article Sci Signal · February 23, 2010 The ability to regenerate damaged tissues is a common characteristic of multicellular organisms. We report a role for apoptotic cell death in promoting wound healing and tissue regeneration in mice. Apoptotic cells released growth signals that stimulated t ... Full text Link to item Cite

In vivo bioluminescence imaging monitoring of hypoxia-inducible factor 1alpha, a promoter that protects cells, in response to chemotherapy.

Journal Article AJR Am J Roentgenol · December 2008 OBJECTIVE: Bioluminescence imaging is a powerful technique that has shown that hypoxia-inducible factor 1 (HIF-1), a transcription factor that protects tumor cells from hypoxia, is up-regulated in tumors after radiation therapy. We tested the hypothesis th ... Full text Link to item Cite

Noninvasive imaging and quantification of epidermal growth factor receptor kinase activation in vivo.

Journal Article Cancer Res · July 1, 2008 Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) critical in tumor growth and a major target for anticancer drug development. However, thus far, there is no effective system to monitor its activities in vivo. Here, we report a no ... Full text Link to item Cite

Regulation of HIF-1alpha stability through S-nitrosylation.

Journal Article Mol Cell · April 13, 2007 Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional factor. Under normal oxygen tension, HIF-1 activity is usually suppressed due to the rapid, oxygen-dependent degradation of one of its two subunits, HIF-1alpha. Here we report that normoxic HIF ... Full text Link to item Cite

Regulation of mammalian horizontal gene transfer by apoptotic DNA fragmentation.

Journal Article Br J Cancer · December 18, 2006 Previously it was shown that horizontal DNA transfer between mammalian cells can occur through the uptake of apoptotic bodies, where genes from the apoptotic cells were transferred to neighbouring cells phagocytosing the apoptotic bodies. The regulation of ... Full text Link to item Cite

Tumor necrosis factor-alpha is a potent endogenous mutagen that promotes cellular transformation.

Journal Article Cancer Res · December 15, 2006 Tumor necrosis factor-alpha (TNF-alpha) is an important inflammation cytokine without known direct effect on DNA. In this study, we found that TNF-alpha can cause DNA damages through reactive oxygen species. The mutagenic effect of TNF-alpha is comparable ... Full text Link to item Cite

Apoptotic DNA fragmentation factor maintains chromosome stability in a P53-independent manner.

Journal Article Oncogene · August 31, 2006 DNA fragmentation factor (DFF)/caspase-activated DNase (CAD) is responsible for DNA fragmentation, a hallmark event during apoptosis. Although DNA fragmentation is an evolutionarily conserved process across species, its biological function is not clearly u ... Full text Link to item Cite

Enhancement of cancer radiation therapy by use of adenovirus-mediated secretable glucose-regulated protein 94/gp96 expression.

Journal Article Cancer Res · October 15, 2005 Tumor-derived glucose-regulated protein 94 (GRP94/gp96) has shown great promise as a tumor vaccine. However, current protein-based approaches require the availability of large quantities of tumor tissue, which are often not possible. In addition, the effic ... Full text Link to item Cite

Enhancement of hypoxia-induced tumor cell death in vitro and radiation therapy in vivo by use of small interfering RNA targeted to hypoxia-inducible factor-1alpha.

Journal Article Cancer Res · November 15, 2004 Hypoxia-inducible factor-1alpha (HIF-1alpha) is an important transcriptional factor that is activated when mammalian cells experience hypoxia, a tumor microenvironmental condition that plays pivotal roles in tumor progression and treatment. In this study, ... Full text Link to item Cite