Fei Chen, Ph.D.
Department of Pharmaceutical Sciences
EACPHS, Wayne State University
259 Mack Avenue, Detroit, MI 48201
• Cancer cell biology and pharmaceutics
• Cancer signaling and epigenetics
• Cancer stem cells and miRNAs
• Histone methylation and lung cancer
• JNK, Stat3, Akt, EZH2, and stem cell reprogramming
The broad focus of the Chen lab is to investigate genetic and epigenetic regulations of genes in human lung cancer related to environmental or occupational exposure to mineral dust and carcinogenic metals. More specifically, the lab employs biochemical approaches to elucidate molecular mechanisms by which the expression and function of genes contributing to lung inflammation and tumorigenesis are altered. One of the key signaling events in carcinogenic gene regulation is the activation of kinases and transcription factors, such as JNK, Stat3, Akt, and NF-kappaB. A principal question to be addressed is how extracellular inducers, such as reactive oxygen species (ROS), cytokines and carcinogenic metals, perturb the intracellular regulatory circuits that control cross-talk, durability and potency of the kinase pathways.
Accumulating evidence suggests that many environmental factors contribute to malignant transformation of the cells through altering intracellular signaling pathways that converge on epigenetic regulation, such as methylation of the histone proteins and DNA, acetylation and ubiquitination of the histone proteins. The status of histone methylation, especially on the N-terminal tails of histones H3 and H4, directly determines the accessibility of the regulatory factors on the genes packed in the condensed chromatin fibers. The Chen lab had previously identified a mineral dust-induced gene, mdig that contains a signature motif of histone demethylases, the JmjC domain. The current effort is to determine whether this gene product possesses the demethylase activity or affects methylation status of the histone proteins through interaction with other nuclear proteins. An addition project is to study how arsenic-activated JNK, Stat3 and Akt regulate expression of miRNAs and phosphorylation of EZH2 that linked to self-renewal of the cancer stem cells.
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;5:1290-303.
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. Toxicol Appl Pharmacol. 2014;276:165-70.
Sun J, Yu M, Lu Y, Thakur C, Chen B, Qiu P, Zhao H, Chen F. Carcinogenic metalloid arsenic induces expression of mdig oncogene through JNK and STAT3 activation. Cancer Lett. 2014;346:257-63.
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;535:218-24.
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;4:1427-37.
Mohammed AM, Chen F, Kowluru A. The Two Faces of Protein Palmitoylation in Islet β-Cell Function: Potential Implications in the Pathophysiology of Islet Metabolic Dysregulation and Diabetes. Recent Pat Endocr Metab Immune Drug Discov. 2013;7:203-12.
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;12:112-21.
Education and Training
1979-1982 Medicine, Nantong Medical College, China
1989-1994 PhD in Immunology, Peking University Health Sciences Center, China
1994-1998 Postdoctoral Fellow, Penn State University, Hershey, Pennsylvania