Mei Chen, PhD

Professor of Dermatology

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Overview

Dr. Chen obtained a Ph.D. in Cell Biology, Virology and Molecular Biology at Albert Einstein College of Medicine in New York. After postdoctoral training in Cell and Developmental Biology at Memorial Sloan-Kettering Cancer Center and Cornell University Medical College, Dr. Chen joined the faculty of the department of Dermatology at Northwestern University Medical School, followed by an appointment at the University of Southern California where she is currently Professor and Director of USC Laboratories for Investigative Dermatology. Dr. Chen’s research has focused on elucidating the structure and function of type VII (anchoring fibril) collagen and developing various therapeutic approaches including cell therapy, small molecule-based drug therapy, protein therapy and gene therapy for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). Her current research plans are 1) to evaluate the effects of recombinant type VII collagen (rC7) on skin wounds in normal and diabetic pigs. This is because it is known that pigskin is the most similar of all species to human skin. This will provide essential data for moving rC7 from the laboratory bench to the patient’s bedside; 2) To determine the signaling pathway(s) responsible for RDEB scarring and identify the mechanism(s) by which rC7 inhibits skin wound scar formation; this work may lead to insights into the pathology of scars and identifiable targets for agents to prevent skin scarring; 3) To evaluate aminoglycoside-based drug therapy for RDEB in human patients; and 4) To identify the changes in RDEB-associated squamous cell carcinoma (SCC) at the cellular and molecular levels and elucidate signaling pathways leading to onset of RDEB SCC that may provide targets for anti-SCC drug development. All of these studies have strong translational potential and will hopefully advance future therapies for patients with RDEB, patients with devastating scarring conditions (burn victims, RDEB patients, keloids, chronic graft-versus-host disease, scleroderma, and others), and patients with chronic non-healing wounds (diabetic ulcers, decubitus ulcers and stasis dermatitis ulcers). The entirety of her work will generate novel insights into cutaneous biology and has great translational potential towards bringing rC7 “from the laboratory bench to the bedside of patients”. Our research programs have been continuously supported by NIH grants for the last twenty years.

Publications

  • Association between Self-Reported Survey Measures and Biomarkers of Second-Hand Tobacco Smoke Exposure in Non-Smoking Pregnant Women Int J Environ Res Public Health. 2021 08 31; 18(17). . View in PubMed
  • Influence of Environmental Tobacco Smoke and Air Pollution on Fetal Growth: A Prospective Study Int J Environ Res Public Health. 2020 07 23; 17(15). . View in PubMed
  • Suppression of TGFß and Angiogenesis by Type VII Collagen in Cutaneous SCC J Natl Cancer Inst. 2016 Jan; 108(1). . View in PubMed
  • Intravenously Administered Recombinant Human Type VII Collagen Derived from Chinese Hamster Ovary Cells Reverses the Disease Phenotype in Recessive Dystrophic Epidermolysis Bullosa Mice J Invest Dermatol. 2015 Dec; 135(12):3060-3067. . View in PubMed
  • A Novel Fully Humanized 3D Skin Equivalent to Model Early Melanoma Invasion Mol Cancer Ther. 2015 Nov; 14(11):2665-73. . View in PubMed
  • Lentiviral Engineered Fibroblasts Expressing Codon Optimized COL7A1 Restore Anchoring Fibrils in RDEB J Invest Dermatol. 2015 Sep 22. . View in PubMed
  • Reduced Toxicity Conditioning and Allogeneic Hematopoietic Progenitor Cell Transplantation for Recessive Dystrophic Epidermolysis BullosaJ Pediatr. 2015 Sep; 167(3):765-9. e1. . View in PubMed
  • Recessive Dystrophic Epidermolysis Bullosa: Advances in the Laboratory Leading to New Therapies J Invest Dermatol. 2015 Jul; 135(7):1705-1707. . View in PubMed
  • Hsp90a and Hsp90ß together operate a hypoxia and nutrient paucity stress-response mechanism during wound healing J Cell Sci. 2015 Apr 15; 128(8):1475-80. . View in PubMed
  • Keratinocyte Migration and a Hypothetical New Role for Extracellular Heat Shock Protein 90 Alpha in Orchestrating Skin Wound Healing Adv Wound Care (New Rochelle). 2015 Apr 01; 4(4):203-212. . View in PubMed
  • Aminoglycosides restore full-length type VII collagen by overcoming premature termination codons: therapeutic implications for dystrophic epidermolysis bullosa Mol Ther. 2014 Oct; 22(10):1741-52. . View in PubMed
  • De novo anti-type VII collagen antibodies in patients with recessive dystrophic epidermolysis bullosa J Invest Dermatol. 2014 Apr; 134(4):1138-1140. . View in PubMed
  • Identification of the critical therapeutic entity in secreted Hsp90a that promotes wound healing in newly re-standardized healthy and diabetic pig models PLoS One. 2014; 9(12):e113956. . View in PubMed
  • Extracellular heat shock protein 90 signals through subdomain II and the NPVY motif of LRP-1 receptor to Akt1 and Akt2: a circuit essential for promoting skin cell migration in vitro and wound healing in vivo Mol Cell Biol. 2013 Dec; 33(24):4947-59. . View in PubMed
  • Intravenously injected recombinant human type VII collagen homes to skin wounds and restores skin integrity of dystrophic epidermolysis bullosa J Invest Dermatol. 2013 Jul; 133(7):1910-3. . View in PubMed
  • Topical application of recombinant type VII collagen incorporates into the dermal-epidermal junction and promotes wound closure Mol Ther. 2013 07; 21(7):1335-44. . View in PubMed
  • Extracellular Hsp90 (eHsp90) as the actual target in clinical trials: intentionally or unintentionally Int Rev Cell Mol Biol. 2013; 303:203-35. . View in PubMed
  • The anti-motility signaling mechanism of TGFß3 that controls cell traffic during skin wound healing Biol Open. 2012 Dec 15; 1(12):1169-77. . View in PubMed
  • A potentially common peptide target in secreted heat shock protein-90a for hypoxia-inducible factor-1a-positive tumors Mol Biol Cell. 2012 Feb; 23(4):602-13. . View in PubMed
  • Epidermolysis bullosa acquisita: autoimmunity to anchoring fibril collagen Autoimmunity. 2012 Feb; 45(1):91-101. . View in PubMed
  • Epidermolysis bullosa acquisita Clin Dermatol. 2012 Jan-Feb; 30(1):60-9. . View in PubMed
  • A fragment of secreted Hsp90a carries properties that enable it to accelerate effectively both acute and diabetic wound healing in mice J Clin Invest. 2011 Nov; 121(11):4348-61. . View in PubMed
  • Congenital epidermolysis bullosa acquisita: vertical transfer of maternal autoantibody from mother to infant Arch Dermatol. 2011 Mar; 147(3):337-41. . View in PubMed
  • TbetaRI/Alk5-independent TbetaRII signaling to ERK1/2 in human skin cells according to distinct levels of TbetaRII expression J Cell Sci. 2011 Jan 01; 124(Pt 1):19-24. . View in PubMed
  • Bone marrow transplantation for recessive dystrophic epidermolysis bullosa N Engl J Med. 2010 Aug 12; 363(7):629-39. . View in PubMed
  • Non-compensating roles between Nckalpha and Nckbeta in PDGF-BB signaling to promote human dermal fibroblast migration J Invest Dermatol. 2009 Aug; 129(8):1909-20. . View in PubMed
  • Participation of the lipoprotein receptor LRP1 in hypoxia-HSP90alpha autocrine signaling to promote keratinocyte migration J Cell Sci. 2009 May 15; 122(Pt 10):1495-8. . View in PubMed
  • TANGO1 facilitates cargo loading at endoplasmic reticulum exit sites Cell. 2009 Mar 06; 136(5):891-902. . View in PubMed
  • Injection of recombinant human type VII collagen corrects the disease phenotype in a murine model of dystrophic epidermolysis bullosa Mol Ther. 2009 Jan; 17(1):26-33. . View in PubMed
  • Familial epidermolysis bullosa acquisita Dermatol Online J. 2008 Dec 15; 14(12):2. . View in PubMed
  • Duplicating autoimmune bullous diseases by passively transferring autoantibodies into animals J Invest Dermatol. 2008 Oct 06; 128(E3):E25-7. . View in PubMed
  • Profiling motility signal-specific genes in primary human keratinocytes J Invest Dermatol. 2008 Aug; 128(8):1981-90. . View in PubMed
  • Characterization of molecular mechanisms underlying mutations in dystrophic epidermolysis bullosa using site-directed mutagenesis J Biol Chem. 2008 Jun 27; 283(26):17838-45. . View in PubMed
  • Transforming growth factor alpha (TGFalpha)-stimulated secretion of HSP90alpha: using the receptor LRP-1/CD91 to promote human skin cell migration against a TGFbeta-rich environment during wound healing Mol Cell Biol. 2008 May; 28(10):3344-58. . View in PubMed
  • Hypoxia induces epidermal keratinocyte matrix metalloproteinase-9 secretion via the protein kinase C pathway J Cell Physiol. 2008 Jan; 214(1):47-55. . View in PubMed
  • Autoimmunity to type VII collagen: epidermolysis bullosa acquisita Curr Dir Autoimmun. 2008; 10:195-205. . View in PubMed
  • Autoimmunity to type VII collagen: epidermolysis bullosa acquisita Clin Rev Allergy Immunol. 2007 Oct; 33(1-2):78-84. . View in PubMed
  • Nckbeta adapter controls neuritogenesis by maintaining the cellular paxillin level Mol Cell Biol. 2007 Sep; 27(17):6001-11. . View in PubMed
  • The cartilage matrix protein subdomain of type VII collagen is pathogenic for epidermolysis bullosa acquisita Am J Pathol. 2007 Jun; 170(6):2009-18. . View in PubMed
  • Extracellular heat shock protein-90alpha: linking hypoxia to skin cell motility and wound healing EMBO J. 2007 Mar 07; 26(5):1221-33. . View in PubMed
  • Intravenously injected human fibroblasts home to skin wounds, deliver type VII collagen, and promote wound healing Mol Ther. 2007 Mar; 15(3):628-35. . View in PubMed
  • Transforming growth factor-alpha: a major human serum factor that promotes human keratinocyte migration J Invest Dermatol. 2006 Sep; 126(9):2096-105. . View in PubMed
  • PKCdelta clustering at the leading edge and mediating growth factor-enhanced, but not ecm-initiated, dermal fibroblast migration J Invest Dermatol. 2006 Jun; 126(6):1233-43. . View in PubMed
  • Induction of epidermolysis bullosa acquisita in mice by passive transfer of autoantibodies from patients J Invest Dermatol. 2006 Jun; 126(6):1323-30. . View in PubMed
  • Fibroblasts as target cells for DEB gene therapy J Invest Dermatol. 2006 Apr; 126(4):708-10. . View in PubMed
  • A “traffic control” role for TGFbeta3: orchestrating dermal and epidermal cell motility during wound healing J Cell Biol. 2006 Mar 27; 172(7):1093-105. . View in PubMed
  • Evidence that anti-type VII collagen antibodies are pathogenic and responsible for the clinical, histological, and immunological features of epidermolysis bullosa acquisita J Invest Dermatol. 2005 May; 124(5):958-64. . View in PubMed
  • Wound-healing perspectives Dermatol Clin. 2005 Apr; 23(2):181-92. . View in PubMed
  • Signals that initiate, augment, and provide directionality for human keratinocyte motility J Invest Dermatol. 2004 Oct; 123(4):622-33. . View in PubMed
  • Intradermal injection of lentiviral vectors corrects regenerated human dystrophic epidermolysis bullosa skin tissue in vivo Mol Ther. 2004 Aug; 10(2):318-26. . View in PubMed
  • A patient with both bullous pemphigoid and epidermolysis bullosa acquisita: an example of intermolecular epitope spreading J Am Acad Dermatol. 2004 Jul; 51(1):118-22. . View in PubMed
  • Epidermolysis bullosa: then and now J Am Acad Dermatol. 2004 Jul; 51(1 Suppl):S55-7. . View in PubMed
  • Injection of recombinant human type VII collagen restores collagen function in dystrophic epidermolysis bullosa Nat Med. 2004 Jul; 10(7):693-5. . View in PubMed
  • Mechanisms of human skin cell motility Histol Histopathol. 2004 10; 19(4):1311-24. . View in PubMed
  • Mechanism of human dermal fibroblast migration driven by type I collagen and platelet-derived growth factor-BB Mol Biol Cell. 2004 Jan; 15(1):294-309. . View in PubMed
  • Normal and gene-corrected dystrophic epidermolysis bullosa fibroblasts alone can produce type VII collagen at the basement membrane zone J Invest Dermatol. 2003 Nov; 121(5):1021-8. . View in PubMed
  • An efficient gene transduction system for studying gene function in primary human dermal fibroblasts and epidermal keratinocytes Clin Exp Dermatol. 2003 Mar; 28(2):193-9. . View in PubMed
  • Restoration of type VII collagen expression and function in dystrophic epidermolysis bullosa Nat Genet. 2002 Dec; 32(4):670-5. . View in PubMed
  • The epidermolysis bullosa acquisita antigen (type VII collagen) is present in human colon and patients with crohn’s disease have autoantibodies to type VII collagen J Invest Dermatol. 2002 Jun; 118(6):1059-64. . View in PubMed
  • Drug-induced epidermolysis bullosa acquisita with antibodies to type VII collagen J Am Acad Dermatol. 2002 May; 46(5 Suppl):S161-4. . View in PubMed
  • An important role for protein kinase C-delta in human keratinocyte migration on dermal collagen Exp Cell Res. 2002 Feb 15; 273(2):219-28. . View in PubMed
  • The recombinant expression of full-length type VII collagen and characterization of molecular mechanisms underlying dystrophic epidermolysis bullosa J Biol Chem. 2002 Jan 18; 277(3):2118-24. . View in PubMed
  • The p38-MAPK/SAPK pathway is required for human keratinocyte migration on dermal collagen J Invest Dermatol. 2001 Dec; 117(6):1601-11. . View in PubMed
  • Epidermolysis bullosa acquisita: update and review Clin Dermatol. 2001 Nov-Dec; 19(6):712-8. . View in PubMed
  • The carboxyl terminus of type VII collagen mediates antiparallel dimer formation and constitutes a new antigenic epitope for epidermolysis Bullosa acquisita autoantibodies J Biol Chem. 2001 Jun 15; 276(24):21649-55. . View in PubMed
  • Autoantibodies to type VII collagen have heterogeneous subclass and light chain compositions and their complement-activating capacities do not correlate with the inflammatory clinical phenotype J Clin Immunol. 2000 Nov; 20(6):416-23. . View in PubMed
  • Nckbeta adapter regulates actin polymerization in NIH 3T3 fibroblasts in response to platelet-derived growth factor bb Mol Cell Biol. 2000 Nov; 20(21):7867-80. . View in PubMed
  • Development and characterization of a recombinant truncated type VII collagen “minigene”Implication for gene therapy of dystrophic epidermolysis bullosa. J Biol Chem. 2000 Aug 11; 275(32):24429-35. . View in PubMed
  • Alpha 2 beta 1 integrin mediates dermal fibroblast attachment to type VII collagen via a 158-amino-acid segment of the NC1 domain Exp Cell Res. 1999 Jun 15; 249(2):231-9. . View in PubMed
  • Bullous systemic lupus erythematosus with autoantibodies recognizing multiple skin basement membrane components, bullous pemphigoid antigen 1, laminin-5, laminin-6, and type VII collagen Arch Dermatol. 1999 May; 135(5):569-73. . View in PubMed
  • NC1 domain of type VII collagen binds to the beta3 chain of laminin 5 via a unique subdomain within the fibronectin-like repeats J Invest Dermatol. 1999 Feb; 112(2):177-83. . View in PubMed
  • Molecular cloning and characterization of a cDNA encoding canine type VII collagen non-collagenous (NC1) domain, the target antigen of autoimmune disease epidermolysis bullosa acquisita (EBA) Biochim Biophys Acta. 1998 Oct 22; 1408(1):25-34. . View in PubMed
  • Epitope spreading: lessons from autoimmune skin diseases J Invest Dermatol. 1998 Feb; 110(2):103-9. . View in PubMed
  • Interactions of the amino-terminal noncollagenous (NC1) domain of type VII collagen with extracellular matrix componentsA potential role in epidermal-dermal adherence in human skin. J Biol Chem. 1997 Jun 06; 272(23):14516-22. . View in PubMed
  • Laminin-6 and laminin-5 are recognized by autoantibodies in a subset of cicatricial pemphigoid J Invest Dermatol. 1997 Jun; 108(6):848-53. . View in PubMed
  • Modulation of type VII collagen (anchoring fibril) expression by retinoids in human skin cells Biochim Biophys Acta. 1997 Apr 10; 1351(3):333-40. . View in PubMed
  • Ultraviolet A irradiation upregulates type VII collagen expression in human dermal fibroblasts J Invest Dermatol. 1997 Feb; 108(2):125-8. . View in PubMed
  • Development of an ELISA for rapid detection of anti-type VII collagen autoantibodies in epidermolysis bullosa acquisita J Invest Dermatol. 1997 Jan; 108(1):68-72. . View in PubMed