Fei Chen

Fei Chen




Pharmaceutical Sciences

Office Location

EACPHS, Room 3603





Fei Chen

Degrees and Certifications

  • 1979-1982 - Medicine, Natong Medical College, P.R. China
  • 1989-1994 - PhD in Immunology, Beijing Medical University, P.R. China
  • 1994-1998 - Postdoctoral Fellow, Penn State University, Hershey, PA, USA

Positions and Employment

  • 1983-1986: Resident physician in Internal Medicine, Qixi municipal hospital, P.R. China
  • 1987-1988: Administrative scientist, Division of Public Health of Qidong County, P.R. China
  • 1994-1997: Postdoctoral Fellow, Department of Pathology, Penn State University, PA
  • 1998-2001: CDC Genetic Fellow, National Institute for Occupational Safety and Health, WV
  • 1999-2003: Adjunct Assistant Professor, Basic Pharmaceutical Sciences, WVU, WV
  • 2001-2008: Senior Service Fellow, National Institute for Occupational Safety and Health, WV
  • 2003-2010: Adjunct Associate Professor, Department of Pathology, WVU, WV
  • 2004-2010: Principal Investigator, National Institute for Occupational Safety and Health, WV
  • 2007: Adjunct Professor, Department of Basic Pharmaceutical Sciences, WVU, WV
  • 2008-2010: Adjunct Associate Professor, Graduate Center for Toxicology, University of Kentucky
  • 2009-2010: Tenured Research Biologist, National Institute for Occupational Safety and Health, WV
  • 2010-2013: Associate Professor with tenure, Department of Pharmaceutical Sciences, Wayne State University, MI
  • 2010-2013: Guest Scientist, National Institute for Occupational Safety and Health, WV
  • 2011-2013: Associate Professor, Cancer Biology Program, Karmanos Cancer Center, Wayne State University, MI
  • 2013-Present: Professor with tenure, Department of Pharmaceutical Sciences, Wayne State University, MI
  • 2013-Present: Professor, Department of Oncology, Karmanos Cancer Center, Wayne State University, MI 

Awards and Honors

  • 1998 - Recipient of Paul E. Strandjord Young Investigator Award
  • 1998-2001 - Recipient of CDC Career Development Award on Genetics
  • 2002 - Nominee of Charles C. Shepard Science Award, CDC
  • 2005 - Nominee of Charles C. Shepard Science Award, CDC

Primary Research Interest

Mdig gene and histone demethylation in lung cancer (1RO1ES017217-01A2)

Lung cancer is the most common cancer worldwide, accounting for 1.3 million cancer deaths annually. Despite extensive efforts to elucidate mechanisms and develop new therapeutic regimens, the worldwide mortality rate of lung cancer remains high. The objective of this project is to investigate the role of Mdig, a mineral dust-induced gene we identified from alveolar macrophages of patients with occupational lung diseases, played on lung cell proliferation and carcinogenic transformation induced by environmental and occupational hazards. The central hypothesis is that Mdig promotes cell growth and transformation by functioning as a histone demethylase that antagonizes tri-methyl lysine 9 on histone H3 (H3K9me3). Down-regulation of H3K9me3 will enhance the expression of genes associated with the cell cycle regulation and malignant transformation in lung epithelial cells. To accomplish the goal of this project, we will: (1) test the potential demethylase activity of mdig protein toward H3K9me3; (2) determine whether the expression of the cell cycle-regulated genes, such as cyclins, Cdc25s and checkpoint proteins, is regulated by the methylation regulation of mdig; and (3) study the tumorigenic effect of mdig by both over-expression and down-regulation of mdig in BEAS-2B cells and A549 cells, respectively, in both cell culture and inoculation of the cells in nude mice. At the completion of this project, it is anticipated that in addition to reveal a previously unknown new mechanism of the human lung cancer, the expression of mdig can be potentially served as a new biomarker and therapeutic target of the human lung cancer.

Arsenic-induced alternative splicing of the GADD45a in carcinogenesis

Environmental arsenic exposure, especially the trivalent form arsenic (As3+), has long been known to be a risk factor for human cancers, including cancers of lung, liver, skin, kidney, and urinary bladder. Despite extensive efforts to elucidate how As3+ causes human cancer, the underlying mechanism remains to be investigated. Our previous studies have shown that (a) As3+ is able to generate reactive oxygen species (ROS) and induces GADD45a, a tumor suppressor protein; (b) As3+ causes alternatively splicing of the GADD45a mRNA to generate a short version of the GADD45a (sG45a) isoform, leading to un-controlled cell growth or disruption of cell growth arrest at G2/M phase; (c) As3+-induced sG45a also inhibits the function of the GADD45a by inhibiting interaction of the GADD45a with CDC2/cyclin B complex; (d) Overexpression of the As3+-induced sG45a can induce cell transformation. Thus, we hypothesize that As3+- induces oxidative stress and causes generation of sG45a, leading to inhibition of GADD45a, disruption of cell growth control, and consequently, the cell transformation and carcinogenesis. Accordingly, we will investigate: (1) how As3+ induces ROS generation with emphasis on the role of NADPH oxidase in human bronchial epithelial cell line, BEAS-2B; (2) how As3+ or its induced ROS affect the assembly of the spliceosome machinery that causes alternative splicing of GADD45a pre-mRNA for the generation of sG45a; (3) the role sG45a in As3+-induced carcinogenesis by overexpression of the sG45a in human bronchial epithelial cells. We will establish stable transfectants and determine the effects of overexpression of sG45a on either basal or As3+-induced cell transformation and carcinogenesis by assays of colony formation in soft agar (anchorage independence) and inoculation of the cells in nude mice. The completion of this project will establish new mechanisms of As3+-induced carcinogenesis in human.

JNK1 and EZH2 in hepatocellular carcinoma

In the United States, hepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related death in men from 1975 to present, despite the fact that the overall cancer mortality rate has declined at the same period. Tremendous efforts to diagnose and institute new treatment regimens have been made in recent years. However, the prognosis of HCC is still extremely poor. Recently, we and others have revealed an important role for c-Jun N-terminal kinase 1 (JNK1) in the pathogenesis of human HCC and its close association with the expression of HCC signature genes. The long-term goal of this project is to develop an innovative HCC treatment regimen based on molecular targeting to JNK1. We hypothesize that the tumor promoting activity of JNK1 in HCC is achieved by directly regulating genes, such as EZH2 and cyclins, that alter the epigenetic landscape of the genome and the transformational potential of the hepatocytes. To test this hypothesis, we will: 1), determine the regulatory role of JNK1 on EZH2 expression and assess the molecular determinants responsible for JNK1 activity on the transcription of EZH2 in hepatocytes and HCC. a), test the hypothesis that JNK1 induces EZH2 through transcriptional regulation of the Ezh2 gene; b), determine whether HCC patients can be stratified based on both JNK1 activation status and the EZH2 expression level; 2), characterize the regulatory role of JNK1 on EZH2 as a key part of its effect on cell cycle control and determine whether the effects of JNK1 on cell cycle are EZH2 dependent in the development of HCC; and 3), test the tumorigenic effect of JNK1 and EZH2 in mouse HCC model: a), tumorigenicity assay using HCC cells in which JNK1 or EZH2 is silenced by shRNA through inoculation of the cells in nude mice; b), using wild-type and JNK1 knockout mice to test the role of JNK1 in liver carcinogenesis in vivo in diethylnitrosamine (DEN)-induced HCC model; and c), investigate therapeutic potential of JNK1 inhibitors for HCC in wild-type mice treated with hepatic carcinogen. At the completion of this project, we expect to have determined the role of JNK1 in the pathogenesis and prognosis of HCC. Based on preliminary studies, we believe that sustained activation of JNK1 is the key for the alteration of epigenetics and genes that cause malignant transformation of the hepatocytes. Furthermore, in addition to reveal a previously understudied role of JNK1 in HCC pathogenesis, it is anticipated that JNK1 activation can potentially serve as a novel therapeutic target.

Professional activities

Reviewer for funding agencies and others

  • Ad hoc reviewer for Oncogene, JNCI, Cancer Res, Cancer Lett, EMBO J, Toxicol. Appl. Pharmacol.,Toxicol Sci., BMC Cancer, Comparative Hepatology, Current Cancer Drug Targets, Gut, Neurotoxicol and Teratol, Emerging Infect Dis, Tumor Biology, PLoS One, Microbiology and Molecular Biology Reviews, Int J Biol Sci, etc. (1999-)
  • External Assessor of Research Grants Council of Hong Kong (2001-)
  • Reviewer, the National Natural Science Foundation of China (2003-2008)
  • Reviewer, the Associazione Italiana per la Ricerca sul Cancro (AIRC) (2005)
  • Reviewer, the Israel Science Foundation (2006-)
  • Section member of tumor cell biology, The Susan G. Komen Breast Cancer Foundation (2005-2007)
  • Expert Reviewer of Dutch Expert Committee on Occupational Standards (DECOS): Platinum and platinum compounds (2008)
  • Reviewer, National Medical Research Council of Singapore (2008-)
  • Reviewer, Italian Ministry of Health in association with NIH (2009-)
  • Scientific reviewer, University of Kentucky Markey Cancer Center (2010)
  • NIH Special Emphasis Panel on Cancer Health Disparities (2001)
  • NIH HBPP Study Section (2012)
  • Scientific reviewer, Wayne State University Karmanos Cancer Center (2012)
  • Member, Data and Safety Monitoring Board, School of Medicine, Wayne State University (2012-2014)
  • NIH/NIEHS ZES1 LWJ-D TG1 Special Emphasis Panel on Understanding Environmental Control of Epigenetic/Mechanisms
  • NIH/NIEHS ZES1 LWJ-K (R) 1 Special Emphasis panel on Neurodegenerative Disorders
  • Ad hoc reviewer, Hollings Cancer Center Translational Research Pilot Project, Medical University of South Carolina
  • NIH/NIEHS ZES1 LWJ-D (ME) 1 Mitochondrial and Nuclear Induced Cross-Talk Perturbations in Response to Environmental Insults

Editorial board member of journals

  • Associate Editor, ATLAS Gene Cytogene Oncol Haematol (2004-2009)
  • Editorial board member, World Journal of Hepatology (2007-2011)
  • Senior editorial board member, American Journal of Cancer Research (2010-)
  • Editorial board member, World Journal of Gastroenterology (2010-2011)
  • Editorial board member, Journal of Cancer Therapeutics and Research (2011-)
  • Guest Editor, Seminars in Cancer Biology (2011-2013)
  • Editorial board member, Occupational Diseases and Environmental Medicine (2011-2013)
  • Editorial board member, Journal of Hepatocellular Carcinoma (2011-2013) 

Recent Publications

1 - Thakur C, Wolfarth M, Sun J, Zhang Y, Lu Y, Battelli L, Porter DW, Chen F*. Oncoprotein mdig contributes to silica-induced pulmonary fibrosis by altering balance between Th17 and Treg T cells. Oncotarget, 2015, in press.

2 - Chang Q, Chen B, Thakur C, Lu Y, Chen F*. Arsenic-induced sub-lethal stress reprograms human bronchial epithelial cells to CD61 cancer stem cells. Oncotarget, 2014, 5: 1290-1303.

3 - Sun J, Yu M, Lu Y, Chen B, Zhao H, Chen F*. JNK and STAT3 signaling contributes to arsenic-induced expression of the mineral dust-induced gene. Cancer Letter, 2014, 346:257-263.

4 - Li L, Qiu P, Chen B, Lu Y, Wu K, Thakur C, Chang Q, Sun J, Chen F*. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells. Toxicology and Applied Pharmacology. 2014, 276: 165-170.

5 - Yu M, Sun J, Chen B, Lu Y, Zhao H, Chen F*. Paradoxical roles of mineral dust induced gene expression on cell proliferation and migration/invasion. PLoS One, 2014, 9(2): e87998.

6 - Thakur C, Lu Y, Sun J, Yu M, Chen B, Chen F*. Increased expression of mdig predicts poorer survival of the breast cancer patients. Gene, 2014, 535:218-224.

7 - Chen B, Yu M, Chang Q, Lu Y, Thakur C, Ma D, Yi Z, Chen F*. Mdig de-represses H19 large intergenic non-coding RNA (lincRNA) by down-regulating H3K9me3 and heterochromatin. Oncotarget. 2013, 4(9):1427-1437.

8 - Wu K, Chang Q, Lu Y, Qiu P, Chen B, Thakur C, Sun J, Li Z, Kowluru A, Chen F*. Gefitinib resistance resulted from STAT3-mediated Akt activation in lung cancer cells. Oncotarget, 2013, 4:2430-2438.

9 - Mohammed AM, Chen F, Kowluru A. The two faces of protein palmitoylation in islet ?-cell function: potential implications in the pathophysiology of islet metabolic dysregulation and diabetes. Recent Pat Endocr Metab Immune Drug Discov. 2013, 7(3):203-12.

10 - Chen JG, LuWZ, Wang LW, Zhang YX, Wang NJ, Chen YS, Zhu J, Zheng HW, Yang J, Chen F*: Cholangiocarcinoma arising 38 years after surgical resection of hepatocellular carcinoma. J. Cancer Therapy. 2013, 4: 953-956.

11 - Chen B, Liu J, Chang Q, Beezhold K, Lu Y, Chen F*: JNK and STAT3 signaling pathways converge on Akt-mediated phosphorylation of EZH2 in bronchial epithelial cells induced by arsenic. Cell Cycle. 2013, 12: 112-121.

12 - Liu J, Chen B, Lu Y, Guan Y, Chen F*: JNK-dependent Stat3 phosphorylation contributes to Akt activation in response to arsenic exposure. Toxicol Sci. 2012, 129: 363-371.

13 - Chen F*: JNK-induced apoptosis, compensatory growth and cancer stem cells. Cancer Res, 2012, 72: 379-386.

14 - Ken H, Wu Z, Yang SH, Chen B, Chen F, Castranova V: Pulmonary exposure of rats to ultrafine titanium dioxide enhances cardiac protein phosphorylation and substance P synthesis in nodose ganglia. Nanotoxicology, 2012, 6: 736-745.

15 - Wang L, Chen F, Zhang Z, Chen G, Luo J, Shi X: Cancer Stem Cells in the Mechanism of Metal Carcinogenesis. J Environ Pathol Toxicol Oncol. 2012, 31:245-263.

16 - Beezhold K, Kan H, Meighan TG, Castranova V, Chen F*: MicroRNA-190 contributes to arsenic-induced Akt activation and cell transformation. Toxicol Sci. 2011, 123:411-420.

17 - Wang X, Son Y, Chang Q, Sun L, Hitron JA, Budhraja A, Zhang Z, Ke Z, Chen F, Luo J, Shi X: NADPH oxidase activation is required in reactive oxygen species generation and cell transformation induced by hexavalent chromium Toxicol. Sci. 2011, 123: 399-410. kfr180

18 - Chen F*: Molecular signature of hepatocellular carcinoma, hope or hype in prognosis and therapy (editorial). Seminars in Cancer Biology, 2011, 21: 1-3.

19 - Beezhold K, Castranova V, Chen F*: Microprocessor of miRNA, regulation and potential for therapeutic intervention. Mol Cancer. 2010, 9: 134.

20 - Chang Q, Pan J, Zhang Z, Chen F*, Shi X*: Reduced capacity of reactive oxygen species generation in the arsenic-transformed cells. Cancer Res, 2010, 70:5127-5135.

21 - Chen F*, Kan H, Castranova V: Methylation of lysine 9 of Histone H3: Role in Heterochromatin Modulation and Tumorigenesis. Handbook of Epigenetics: The New Molecular and Medical Genetics. Edited by Dr. Trygve Tollefsbol, Elsevier, 2010, p149-158.

22 - Pan J, Chang Q, Wang X, Son Y, Zhang Z, Chen G, Luo J, Bi Y, Chen F, Shi X: Reactive oxygen species-activated Akt/ASK1/p38 signaling pathway in nickel compound-induced apoptosis in BEAS 2B cells. Chem Res Toxicol. 2010, 23:568-77.

23 - Chen F*, Beezhold K, Castranova V: JNK1, a potential therapeutic target for hepatocellular carcinoma. BBA-Rev Cancer. 2009, 1796: 242-251.

24 - Chen F*, Li S, Castranova V: Signature genes for both hepatoblastoma and hepatocellular carcinoma (Letters to the Editor). Eur J Gastroen Hepat. 2009, 21: 1220-1222.

25 - Chen F*, Li S, Castranova V: Overlapping Signature Genes between Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma (Letters to the Editor). Eur J Gastroen Hepat. 2009, 21: 1320-1321.

26 - Chang Q, Chen J, Beezhold KJ, Castranova V, Shi X, Chen F*: JNK1 activation predicts the prognostic outcome of the human hepatocellular carcinoma. Mol Cancer.. 2009, 8:64 (p1-14).

27 - Chen F*, Castranova V: Beyond apoptosis of JNK1 in human hepatocellular carcinoma. Cell Cycle. 2009, 8: 1-3.

28 - Chang Q, Zhang Y, Beezhold KJ, Bhatia D, Zhao H, Chen J, Castranova V, Shi X, Chen F*. Sustained JNK1 activation is associated with altered histone H3 methylations in human liver cancer. J Hepatol. 2009, 50:323-333.

29 - Lu Y, Chang Q, Zhang Y, Beezhold K, Rojanasakul Y, Zhao H, Castranova V, Shi X, Chen F*: Lung cancer-associated JmjC domain protein mdig suppresses formation of tri-methyl lysine 9 of histone H3. Cell Cycle. 2009, 8: 2101-2109.

30 - Zhang Y, Beezhold K, Castranova V, Shi X, Chen F*. Characterization of an alternatively spliced GADD45a, GADD45a1 isoform, in arsenic-treated epithelial cells. Mol Carcinogen. 2009, 48: 454-464.

31 - Chen F*, Beezhold K, Castranova V. Tumor promoting or tumor suppressing of NF-kappaB, a matter of cell context dependency. Int Rev Immunol. 2008, 27: 183-204.

32 - Wang L, Azad N, Kongkaneramit L, Chen F, Lu Y, Jiang BH, Rojanasakul Y. The Fas death signaling pathway connecting reactive oxygen species generation and FLICE inhibitory protein down-regulation. J Immunol. 2008, 180(5):3072-80.

33 - Chen F*, Castranova V. Nuclear factor-kappaB, an unappreciated tumor suppressor. Cancer Res. 2007, 67(23):11093-8.

34 - Chang Q, Bhatia D, Zhang Y, Meighan T, Castranova V, Shi X, Chen F*.Incorporation of an internal ribosome entry site-dependent mechanism in arsenic-induced GADD45 alpha expression. Cancer Res. 2007, 67(13):6146-54.

35 - Chen F*, Lu Y, Castranova V, Li Z, Karin M. Loss of Ikkbeta promotes migration and proliferation of mouse embryo fibroblast cells. J Biol Chem. 2006, 281(48):37142-9.

36 - Zhang Y, Bhatia D, Xia H, Castranova V, Shi X, Chen F*. Nucleolin links to arsenic-induced stabilization of GADD45alpha mRNA. Nucleic Acids Res. 2006, 34(2):485-95.

37 - Chen F*, Bhatia D, Chang Q, Castranova V. Finding NEMO by K63-linked polyubiquitin chain.Cell Death Differ. 2006, 13:1835-8.

38 - Bower JJ, Leonard SS, Chen F, Shi X. As(III) transcriptionally activates the gadd45a gene via the formation of H2O2. Free Radic Biol Med. 2006, 41(2):285-94.

39 - Lu B, Wang L, Stehlik C, Medan D, Huang C, Hu S, Chen F, Shi X, Rojanasakul Y. Phosphatidylinositol 3-kinase/Akt positively regulates Fas (CD95)-mediated apoptosis in epidermal Cl41 cells. J Immunol. 2006, 176(11):6785-93.

40 - Zhang Y, Lu Y, Ding M, Castranova V, Shi X, Chen F*.Deficiency in Ikkbeta gene enhances arsenic-induced gadd45alpha expression. Mol Cell Biochem. 2005, 279(1-2):163-8.

41 - Zhang Y, Lu Y, Yuan BZ, Castranova V, Shi X, Stauffer JL, Demers LM, Chen F*. The Human mineral dust-induced gene, mdig, is a cell growth regulating gene associated with lung cancer. Oncogene. 2005, 24(31):4873-82.

42 - Chen F*. Is NF-kappaB a culprit in type 2 diabetes? Biochem Biophys Res Commun. 2005, 332(1):1-3.

43 - Zheng X, Zhang Y, Chen YQ, Castranova V, Shi X, Chen F*.Inhibition of NF-kappaB stabilizes gadd45alpha mRNA. Biochem Biophys Res Commun. 2005, 329(1):95-9.

44 - Li X, Wang G, Zhao J, Ding H, Cunningham C, Chen F, Flynn DC, Reed E, Li QQ. Antiproliferative effect of beta-elemene in chemoresistant ovarian carcinoma cells is mediated through arrest of the cell cycle at the G2-M phase. Cell Mol Life Sci. 2005, 62(7-8):894-904.

45 - Zhang P, Gao W, Li H, Reed E, Chen F*. Inducible degradation of checkpoint kinase 2 links to cisplatin-induced resistance in ovarian cancer cells. Biochem Biophys Res Commun. 2005, 328(2):567-72.

46 - Chen F*. Endogenous inhibitors of nuclear factor-kappaB, an opportunity for cancer control. Cancer Res. 2004, 64(22):8135-8.

47 - Chen F*. Arresting NF-kB by b-arrestin2. Cell Death and Differentiation 2004, 11: 1155-1156.

48 - Wang S, Chen F, Zhang Z, Jiang BH, Jia L, Shi X. NF-kappaB prevents cells from undergoing Cr(VI)-induced apoptosis. Mol Cell Biochem. 2004, 255(1-2):129-37.

49 - Chen F*, Castranova V, Li Z, Karin M, Shi X. Inhibitor of nuclear factor kappaB kinase deficiency enhances oxidative stress and prolongs c-Jun NH2-terminal kinase activation induced by arsenic. Cancer Res. 2003, 63(22):7689-93.

50 - Chen F* and Castranova V. Reactive oxygen species in the activation and regulation of intracellular signaling events. Oxygen/nitrogen redicals: Lung injury and diseases. Edited by Dr. Vallyathan V. Marcel Dekkov Publisher, 2003, 59-90.

51 - Chen F* and Vallyathan V: Molecular mechanisms of asbestos- and silica-induced lung cancer. Phytopharmaceuticals in Cancer Chemoprevention. Edited by Dr. Bagchi D. CRC Press. 2003, 1-55.

52 - Zeidler PC, Roberts JR, Castranova V, Chen F, Butterworth L, Andrew ME, Robinson VA, Porter DW. Response of alveolar macrophages from inducible nitric oxide synthase knockout or wild-type mice to an in vitro lipopolysaccharide or silica exposure. J Toxicol Environ Health A. 2003, 66(11):995-1013.

53 - Chen F*, Demers LM, Shi X. Upstream signal transduction of NF-kappaB activation. Curr Drug Targets Inflamm Allergy. 2002, 1(2):137-49.

54 - Zhang Z, Chen F, Huang C, Shi X. Vanadate induces G2/M phase arrest in p53-deficient mouse embryo fibroblasts. J Environ Pathol Toxicol Oncol. 2002, 21(3):223-31.

55 - Chen F*, Shi X. Signaling from toxic metals to NF-kappaB and beyond: not just a matter of reactive oxygen species. Environ Health Perspect. 2002, 110 Suppl 5:807-11.

56 - Lu B, Wang L, Medan D, Toledo D, Huang C, Chen F, Shi X, Rojanasakul Y. Regulation of Fas (CD95)-induced apoptosis by nuclear factor-kappaB and tumor necrosis factor-alpha in macrophages. Am J Physiol Cell Physiol. 2002, 283(3):C831-8.

57 - Chen F, Shi X. NF-kappaB, a pivotal transcription factor in silica-induced diseases. Mol Cell Biochem. 2002, 234-235(1-2):169-76.

58 - Zhang Z, He H, Chen F, Huang C, Shi X. MAPKs mediate S phase arrest induced by vanadate through a p53-dependent pathway in mouse epidermal C141 cells. Chem Res Toxicol. 2002, 15(7):950-6.

59 - Chen F, Shi X. Intracellular signal transduction of cells in response to carcinogenic metals. Crit Rev Oncol Hematol. 2002, 42(1):105-21.

60 - Chen F*, Zhang Z, Bower J, Lu Y, Leonard SS, Ding M, Castranova V, Piwnica-Worms H, Shi X. Arsenite-induced Cdc25C degradation is through the KEN-box and ubiquitin-proteasome pathway. Proc Natl Acad Sci U S A. 2002, 99(4):1990-5.

61 - Chen F*, Van Dyke K, Vallyathan V, Castranova V, and Shi X. Luciferase assay: a powerful toll to determine toxic metal-induced NF-kB activation. Luminescence Biotechnology Instruments and Applications. Edited by Van Dyke K, Van Dyke C and Woodfork K. CRC Press. 2002, 231-246.

62 - Chen F, Bower J, Leonard SS, Ding M, Lu Y, Rojanasakul Y, Kung HF, Vallyathan V, Castranova V, Shi X. Protective roles of NF-kappa B for chromium(VI)-induced cytotoxicity is revealed by expression of Ikappa B kinase-beta mutant. J Biol Chem. 2002, 277(5):3342-9.

63 - Ding M, Chen F, Shi X, Yucesoy B, Mossman B, Vallyathan V. Diseases caused by silica: mechanisms of injury and disease development. Int Immunopharmacol. 2002, 2(2-3):173-82.

64 - Shi X, Ding M, Chen F, Vallyathan V, and Castranova V. Reactive oxygen species and silica-induced carcinogenesis. Environmental Stressors in Health and Diseases. Edited by Fuchs J and Packer L. Marcel Dekker Publisher, 2001, 203-223.

65 - Swaroop N, Chen F, Wang L, Dokka S, Toledo D, Rojanasakul Y. Inhibition of nuclear transcription factor-kappaB by specific IkappaB kinase peptide inhibitor. Pharm Res. 2001, 18(11):1631-3.

66 - Qian Y, Jiang BH, Flynn DC, Leonard SS, Wang S, Zhang Z, Ye J, Chen F, Wang L, Shi X. Cr (VI) increases tyrosine phosphorylation through reactive oxygen species-mediated reactions. Mol Cell Biochem. 2001, 222(1-2):199-204.

67 - Chen F, Vallyathan V, Castranova V, Shi X. Cell apoptosis induced by carcinogenic metals. Mol Cell Biochem. 2001, 222(1-2):183-8.

68 - Chen F, Ding M, Castranova V, Shi X. Carcinogenic metals and NF-kappaB activation. Mol Cell Biochem. 2001, 222(1-2):159-71.

69 - Liu K, Husler J, Ye J, Leonard SS, Cutler D, Chen F, Wang S, Zhang Z, Ding M, Wang L, Shi X. On the mechanism of Cr (VI)-induced carcinogenesis: dose dependence of uptake and cellular responses. Mol Cell Biochem. 2001, 222(1-2):221-9.

70 - Shi X, Ding M, Chen F, Wang L, Rojanasakul Y, Vallyathan V, Castranova V. Reactive oxygen species and molecular mechanism of silica-induced lung injury. J Environ Pathol Toxicol Oncol. 2001, 20 Suppl 1:85-93.

71 - Chen F*, Castranova V, Shi X. New insights into the role of nuclear factor-kappaB in cell growth regulation. Am J Pathol. 2001, 159(2):387-97.

72 - Chen F, Zhang Z, Leonard SS, Shi X. Contrasting roles of NF-kappaB and JNK in arsenite-induced p53-independent expression of GADD45alpha. Oncogene. 2001, 20(27):3585-9.

73 - Chen F*, Lu Y, Zhang Z, Vallyathan V, Ding M, Castranova V, Shi X. Opposite effect of NF-kappa B and c-Jun N-terminal kinase on p53-independent GADD45 induction by arsenite. J Biol Chem. 2001, 276(14):11414-9.

74 - Dokka S, Malanga CJ, Shi X, Chen F, Castranova V, Rojanasakul Y. Inhibition of endotoxin-induced lung inflammation by interleukin-10 gene transfer in mice. Am J Physiol Lung Cell Mol Physiol. 2000, 279(5):L872-7.

75 - Chen F, Ding M, Lu Y, Leonard SS, Vallyathan V, Castranova V, Shi X. Participation of MAP kinase p38 and IkappaB kinase in chromium (VI)-induced NF-kappaB and AP-1 activation. J Environ Pathol Toxicol Oncol. 2000, 19(3):231-8.

76 - Chen F*, Demers LM, Vallyathan V, Lu Y, Castranova V, Shi X. Impairment of NF-kappaB activation and modulation of gene expression by calpastatin. Am J Physiol Cell Physiol. 2000, 279(3):C709-16.

77 - Chen F*, Demers LM, Vallyathan V, Lu Y, Castranova V, Shi X. Involvement of 5'-flanking kappaB-like sites within bcl-x gene in silica-induced Bcl-x expression. J Biol Chem. 1999, 274(50):35591-5.

78 - Rojanasakul Y, Ye J, Chen F, Wang L, Cheng N, Castranova V, Vallyathan V, Shi X. Dependence of NF-kappaB activation and free radical generation on silica-induced TNF-alpha production in macrophages. Mol Cell Biochem. 1999, 200(1-2):119-25.

79 - Ding M, Shi X, Dong Z, Chen F, Lu Y, Castranova V, Vallyathan V. Freshly fractured crystalline silica induces activator protein-1 activation through ERKs and p38 MAPK. J Biol Chem. 1999, 274(43):30611-6.

80 - Shi X, Ding M, Dong Z, Chen F, Ye J, Wang S, Leonard SS, Castranova V, Vallyathan V. Antioxidant properties of aspirin: characterization of the ability of aspirin to inhibit silica-induced lipid peroxidation, DNA damage, NF-kappaB activation, and TNF-alpha production. Mol Cell Biochem. 1999, 199(1-2):93-102.

81 - Cheng N, Shi X, Ye J, Castranova V, Chen F, Leonard SS, Vallyathan V, Rojanasakul Y. Role of transcription factor NF-kappaB in asbestos-induced TNFalpha response from macrophages. Exp Mol Pathol. 1999, 66(3):201-10.

82 - Chen F*, Demers LM, Vallyathan V, Ding M, Lu Y, Castranova V, Shi X. Vanadate induction of NF-kappaB involves IkappaB kinase beta and SAPK/ERK kinase 1 in macrophages. J Biol Chem. 1999, 274(29):20307-12.

83 - Chen F*, Lu Y, Castranova V, Rojanasakul Y, Miyahara K, Shizuta Y, Vallyathan V, Shi X, Demers LM. Nitric oxide inhibits HIV tat-induced NF-kappaB activation. Am J Pathol. 1999, 155(1):275-84.

84 - Shi X, Dong Z, Huang C, Ma W, Liu K, Ye J, Chen F, Leonard SS, Ding M, Castranova V, Vallyathan V. The role of hydroxyl radical as a messenger in the activation of nuclear transcription factor NF-kappaB. Mol Cell Biochem. 1999, 194(1-2):63-70.

85 - Ding M, Dong Z, Chen F, Pack D, Ma WY, Ye J, Shi X, Castranova V, Vallyathan V. Asbestos induces activator protein-1 transactivation in transgenic mice. Cancer Res. 1999, 59(8):1884-9.

86 - Chen F*, Castranova V, Shi X, Demers LM. New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases. Clin Chem. 1999, 45(1):7-17.

87 - Chen F, Lu Y, Demers LM, Rojanasakul Y, Shi X, Vallyathan V, Castranova V. Role of hydroxyl radical in silica-induced NF-kappa B activation in macrophages. Ann Clin Lab Sci. 1998, 28(1):1-13.

88 - Chen F, Lu Y, Kuhn DC, Maki M, Shi X, Sun SC, Demers LM. Calpain contributes to silica-induced I kappa B-alpha degradation and nuclear factor-kappa B activation. Arch Biochem Biophys. 1997, 342(2):383-8.

89 - Chen F, Sun S, Kuhn DC, Gaydos LJ, Shi X, Lu Y, Demers LM. Involvement of NF-kappaB in silica-induced cyclooxygenase II gene expression in rat alveolar macrophages. Am J Physiol. 1997, 272(4 Pt 1):L779-86.

90 - Chen F, Ye J, Zhang X, Rojanasakul Y, Shi X. One-electron reduction of chromium(VI) by alpha-lipoic acid and related hydroxyl radical generation, dG hydroxylation and nuclear transcription factor-kappaB activation. Arch Biochem Biophys. 1997, 338(2):165-72.

91 - Chen F, Sun S, Kuhn DC, Lu Y, Gaydos LJ, Shi X, Demers LM. Tetrandrine inhibits signal-induced NF-kappa B activation in rat alveolar macrophages. Biochem Biophys Res Commun. 1997, 231(1):99-102.

92 - Chen F, Kuhn DC, Gaydos LJ, Demers LM. Induction of nitric oxide and nitric oxide synthase mRNA by silica and lipopolysaccharide in PMA-primed THP-1 cells. APMIS. 1996, 104(3):176-82.

93 - He SP, Huang DG, Deng HY, Chen F, Zhang H , Cao JT. Application and RIA of insulin-like growth factor. Chinese Journal of Radiology. 1996, 16:127-128.

94 - Chen F, Sun SC, Kuh DC, Gaydos LJ, Demers LM. Essential role of NF-kappa B activation in silica-induced inflammatory mediator production in macrophages. Biochem Biophys Res Commun. 1995, 214(3):985-92.

95 - Chen F, Kuhn DC, Sun SC, Gaydos LJ, Demers LM. Dependence and reversal of nitric oxide production on NF-kappa B in silica and lipopolysaccharide-induced macrophages. Biochem Biophys Res Commun. 1995, 214(3):839-46.

96 - Chen F, Deng HY, Ding GF, Houng DW, Deng YL, Long ZZ. Excessive production of insulin-like growth factor-I by silicotic rat alveolar macrophages. APMIS. 1994, 102(8):581-8.

97 - Chen F, Deng HY, Long ZZ, et al. Identification and purification of IGF-I from silicotic rat alveolar macrophage culture supernatant. Chinese Journal of Occupational Health. 1994, 10:10-13.

98 - Chen F, Deng HY, Long ZZ, et al. Membrane-associated IL-1 and TNF-? on activated murine peritoneal macrophages. Chinese Journal of Immunology. 1994, 14:395-398.

99 - Chen F, Deng HY, Long ZZ, et al. Insulin-like growth factor-I from rat alveolar macrophages is responsible for lung silicosis. Chinese Journal of Microbiology and Immunology. 1994, 102:581-588.

100 - Chen F, Deng HY, Long ZZ, et al. Synergistic effect assay of IL-1, PDGF and insulin on fibroblast proliferation. Chinese Journal of Immunology. 1993, 9:97-100.

101 - Chen F, Deng HY, Long ZZ, et al. Detection of IGF-I in silicotic rat alveolar macrophage supernatant. Chinese Journal of Immunology. 1993, 11:257-260.

102 - Chen F, Deng HY, Long ZZ, et al. Human alveolar macrophages produce growth factors for human embryo lung fibroblasts. Chinese Journal of Immunology. 1992, 15:225-229.

103 - Chen F, Deng HY, Long ZZ, et al. Analysis of IL-1, TNF-? and promoting fibroblast growth activities in silicotic rat alveolar macrophage supernatant. Chinese Journal of Immunology. 1992, 12:379-382.

104 - Chen F, Deng H, Long ZZ. Recent progress on studies of the cytokine receptor superfamily. International Journal of Immunology (Chinese). 1992, 5: 225-229.

105 - Chen F, Deng HY, Long ZZ, et al. Growth regulation effect of human IL-1 on rat lung fibroblast in vitro. Chinese Journal of Immunology (Chinese). 1991, 7:158-160.

106 - Chen F, Deng H, Long ZZ. Interleukin-10, an inhibitor for cytokine synthesis. International Journal of Immunology (Chinese). 1991, 2: 57-60.

107 - Chen F, Deng H, Long ZZ. Molecular characteristics and biological effects of the human monocyte chemokine. International Journal of Immunology (Chinese). 1991, 3: 113-116.

108 - Chen F, Deng H, Long ZZ. Functional characteristics of Lck gene product in T cell activation. International Journal of Immunology (Chinese). 1991, 3: 116-120.

109 - Chen F, Deng H, Long ZZ. Role of Interleukin-9/p40 in B cell function. International Journal of Immunology (Chinese). 1991, 5: 228-231.

110 - Chen F, Yan J, Deng H, Long ZZ. Biological functions of the interleukin-8. International Journal of Immunology (Chinese). 1990, 6: 281-285.

111 - Chen F, Zhou YX. Early events of T lymphocyte activation. International Journal of Immunology (Chinese). 1989, 2: 65-69.