Publications
47 results found
Higgins CA, 2014, Interrogating the integument: the role of the epidermis in hair induction, EXPERIMENTAL DERMATOLOGY, Vol: 23, Pages: 714-715, ISSN: 0906-6705
Xing L, Dai Z, Jabbari A, et al., 2014, Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition, Nature Medicine, Vol: 20, Pages: 1043-1049, ISSN: 1078-8956
Alopecia areata (AA) is a common autoimmune disease resulting from damage of the hair follicle by T cells. The immune pathways required for autoreactive T cell activation in AA are not defined limiting clinical development of rational targeted therapies1. Genome-wide association studies (GWAS)2 implicated ligands for the NKG2D receptor (product of the KLRK1 gene) in disease pathogenesis. Here, we show that cytotoxic CD8+NKG2D+ T cells are both necessary and sufficient for the induction of AA in mouse models of disease. Global transcriptional profiling of mouse and human AA skin revealed gene expression signatures indicative of cytotoxic T cell infiltration, an interferon-γ (IFN-γ) response and upregulation of several γ-chain (γc) cytokines known to promote the activation and survival of IFN-γ–producing CD8+NKG2D+ effector T cells. Therapeutically, antibody-mediated blockade of IFN-γ, interleukin-2 (IL-2) or interleukin-15 receptor β (IL-15Rβ) prevented disease development, reducing the accumulation of CD8+NKG2D+ T cells in the skin and the dermal IFN response in a mouse model of AA. Systemically administered pharmacological inhibitors of Janus kinase (JAK) family protein tyrosine kinases, downstream effectors of the IFN-γ and γc cytokine receptors, eliminated the IFN signature and prevented the development of AA, while topical administration promoted hair regrowth and reversed established disease. Notably, three patients treated with oral ruxolitinib, an inhibitor of JAK1 and JAK2, achieved near-complete hair regrowth within 5 months of treatment, suggesting the potential clinical utility of JAK inhibition in human AA.
Higgins CA, Petukhova L, Harel S, et al., 2014, FGF5 is a crucial regulator of hair length in humans, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 111, Pages: 10648-10653, ISSN: 0027-8424
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- Citations: 104
Eungdamrong NJ, Higgins C, Guo Z, et al., 2014, Challenges and promises in modeling dermatologic disorders with bioengineered skin, Exp Biol Med (Maywood)
The tremendous cost of drug development is often attributed to the long time interval between identifying lead compounds in preclinical studies to assessing clinical efficacy in randomized clinical trials. Many candidate molecules show promise in cell culture or animal models, only to fail in late stage in human investigations. There is a need for novel technologies that allow investigators to quickly and reliably predict drug safety and efficacy. The advent of microtechnology has made it possible to integrate multiple microphysiologic organ systems into a single microfabricated chip. This review focuses on three-dimensional engineered skin, which has enjoyed a long history of uses both in clinical treatments of refractory ulcers and as a laboratory model. We discuss current biological and engineering challenges in construction of a robust bioengineered skin and provide a blueprint for its potential utility to model dermatologic disorders such as psoriasis or cutaneous drug reactions.
Furniss M, Higgins CA, Martinez-Mir A, et al., 2014, Identification of Distinct Mutations in <i>AAGAB</i> in Families with Type 1 Punctate Palmoplantar Keratoderma, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 134, Pages: 1749-1752, ISSN: 0022-202X
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- Citations: 8
Bhogal RK, Mouser PE, Higgins CA, et al., 2014, Protease activity, localization and inhibition in the human hair follicle, INTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Vol: 36, Pages: 46-53, ISSN: 0142-5463
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- Citations: 8
Higgins CA, Christiano AM, 2014, Regenerative medicine and hair loss: how hair follicle culture has advanced our understanding of treatment options for androgenetic alopecia, REGENERATIVE MEDICINE, Vol: 9, Pages: 101-111, ISSN: 1746-0751
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- Citations: 21
Guo Z, Higgins CA, Gillette BM, et al., 2013, Building a microphysiological skin model from induced pluripotent stem cells, STEM CELL RESEARCH & THERAPY, Vol: 4
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- Citations: 30
Higgins CA, Chen JC, Cerise JE, et al., 2013, Microenvironmental reprogramming by three-dimensional culture enables dermal papilla cells to induce de novo human hair-follicle growth, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 110, Pages: 19679-19688, ISSN: 0027-8424
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- Citations: 227
Itoh M, Umegaki-Arao N, Guo Z, et al., 2013, Generation of 3D Skin Equivalents Fully Reconstituted from Human Induced Pluripotent Stem Cells (iPSCs), PLOS ONE, Vol: 8, ISSN: 1932-6203
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- Citations: 142
Hill RP, Gledhill K, Gardner A, et al., 2012, Generation and Characterization of Multipotent Stem Cells from Established Dermal Cultures, PLOS ONE, Vol: 7, ISSN: 1932-6203
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- Citations: 35
Higgins CA, Itoh M, Inoue K, et al., 2012, Reprogramming of Human Hair Follicle Dermal Papilla Cells into Induced Pluripotent Stem Cells, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 132, Pages: 1725-1727, ISSN: 0022-202X
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- Citations: 23
De Berker D, Higgins CA, Jahoda C, et al., 2012, Biology of Hair and Nails, Dermatology, 3rd Edition, Editors: Bolognia, Jorizzo, Schaffer, Publisher: Elsevier Publishing, ISBN: 9780723435716
Better comprehend the clinical-pathological relationship of skin disease with increased histologic coverage. Bolognia's Dermatology is the ultimate multimedia reference for residents in training AND the experienced practitioner.
Higgins CA, Westgate GE, Jahoda CAB, 2011, Modulation in Proteolytic Activity Is Identified as a Hallmark of Exogen by Transcriptional Profiling of Hair Follicles, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 131, Pages: 2349-2357, ISSN: 0022-202X
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- Citations: 12
Higgins CA, Richardson GD, Ferdinando D, et al., 2010, Modelling the hair follicle dermal papilla using spheroid cell cultures, EXPERIMENTAL DERMATOLOGY, Vol: 19, Pages: 546-548, ISSN: 0906-6705
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- Citations: 88
Higgins CA, Westgate GE, Jahoda CAB, 2009, From Telogen to Exogen: Mechanisms Underlying Formation and Subsequent Loss of the Hair Club Fiber, JOURNAL OF INVESTIGATIVE DERMATOLOGY, Vol: 129, Pages: 2100-2108, ISSN: 0022-202X
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- Citations: 59
Higgins CA, Richardson GD, Westgate GE, et al., 2009, Exogen involves gradual release of the hair club fibre in the vibrissa follicle model, EXPERIMENTAL DERMATOLOGY, Vol: 18, Pages: 793-795, ISSN: 0906-6705
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- Citations: 8
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