Dermal Cell News Volume 5.35 | Oct 21 2019

TOP STORY

Keratinocyte-Derived IκBζ Drives Psoriasis and Associated Systemic Inflammation

Scientists found that IκBζ expression in keratinocytes triggered not only skin lesions, but also systemic inflammation in mouse psoriasis models. Specific depletion of IκBζ in keratinocytes was sufficient to suppress the induction of imiquimod- or IL-36-mediated psoriasis. [J Clin Invest] Abstract | Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

IRF2 Is a Master Regulator of Human Keratinocyte Stem Cell Fate

Researchers investigated whether transcriptional circuitry also governed phenotypic changes within a given cell type by comparing human primary keratinocytes with intrinsically high versus low stem cell potential. Using integrated chromatin and transcriptional profiling, they implicated interferon regulatory factor 2 (IRF2) as antagonistic to stemness and showed that it bound and regulated active cis-regulatory elements at interferon response and antigen presentation genes. [Nat Commun] Full Article

KLF4 Inhibition Promotes the Expansion of Keratinocyte Precursors from Adult Human Skin and of Embryonic-Stem-Cell-Derived Keratinocytes

The authors showed that stable and transient downregulation of the transcription factor Krüppel-like factor 4 (KLF4) in keratinocyte precursors from adult skin, using anti-KLF4 RNA interference or kenpaullone, promoted keratinocyte immaturity and keratinocyte self-renewal in vitro, and enhanced the capacity for epidermal regeneration in mice. [Nat Biomed Eng] Abstract

17-Oxo-Docosahexaenoic Acid Induces Nrf2-Mediated Expression of Heme Oxygenase-1 in Mouse Skin In Vivo and in Cultured Murine Epidermal Cells

The effects of 17-oxo-docosahexaenoic acid (17-oxo-DHA) on Nrf2-mediated expression of cytoprotective enzymes were examined in mouse skin in vivo and cultured murine epidermal JB6 cells. Topical application of 17-oxo-DHA markedly elevated the nuclear localization of Nrf2 and expression of heme oxygenase and NAD(P)H:quinone oxidoreductase in hairless mouse skin. [Arch Biochem Biophys] Abstract

Constituents of the Leaves and Twigs of Elaeagnus umbellata and Their Proliferative Effects on Human Keratinocyte HaCaT Cells

Bioassay-guided fractionation of an extract of leaves and twigs of E. umbellata led to the isolation of a serotonin derivative, N-[2-(5-hydroxyl-1H-indol-3-yl)ethyl]-butanamide, along with six flavonoid glycosides. Their structures were elucidated using 1D/2D nuclear magnetic resonance spectroscopy and mass spectrometry. Six compounds were evaluated for their proliferative effects on HaCaT keratinocytes; five compounds promoted keratinocyte proliferation dose dependently. [Fitoterapia] Abstract | Graphical Abstract

SKIN CANCERS & DISORDERS

Genetic Heterogeneity of BRAF Fusion Kinases in Melanoma Affects Drug Responses

Investigators identified six melanoma lines harboring BRAF fusions representative of the clinical cases reported in the literature. Their unexpected heterogeneous responses to RAF and MEK inhibitors could be categorized upon specific features of the fusion kinases. [Cell Rep] Full Article | Graphical Abstract

Inhibition of p38/MK2 Signaling Prevents Vascular Invasion of Melanoma

Signaling pathways involved in this switch were analyzed by gene expression profiling of a cohort of 22 patient-derived melanoma cell lines. E-cadherin/CDH1 negativity was identified as a surrogate marker for the invasive phenotype. [J Invest Dermatol] Abstract | Graphical Abstract

TNFα-Signal and cAMP-Mediated Signals Oppositely Regulate Melanoma-Associated Ganglioside GD3 Synthase Gene in Human Melanocytes

Investigators analyzed the expression and regulatory mechanisms of glycosyltransferase genes responsible for ganglioside synthesis in normal melanocytes. They reported previously that culture supernatants of UVB-irradiated keratinocytes induced upregulation of ganglioside GD3 synthase gene in melanocytes, and mainly TNFα was responsible for it. [Sci Rep] Full Article

Loss of the Dermis Zinc Transporter ZIP13 Promotes the Mildness of Fibrosarcoma by Inhibiting Autophagy

Researchers focused on the role of a recently-found dermis zinc transporter, ZIP13, in fibrosarcoma progression. They generated two transformed cell lines from wild-type and ZIP13-KO mice-derived dermal fibroblasts by stably expressing the simian virus 40-T antigen. The ZIP13^−/− cell line exhibited an impairment in autophagy, followed by hypersensitivity to nutrient deficiency. [Sci Rep] Full Article

Evaluation of Polyamines as Marker of Melanoma Cell Proliferation and Differentiation by an Improved High-Performance Liquid Chromatographic Method

The authors showed a simply and highly reproducible reverse-phase high-performance liquid chromatographic method for the determination of ortho-phthalaldehyde derivatives of polyamines: putrescine, cadaverine, spermidine and spermine. [Amino Acids] Abstract

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A Review of Accelerated Wound Healing Approaches: Biomaterial-Assisted Tissue Remodeling

The authors discuss tissue remodeling phenomena, wound healing mechanisms, and their related factors. In addition, they review different methods for induction and acceleration of healing via cell therapy, bioactive therapeutic delivery, and/or biomaterial-based approaches. [J Mater Sci] Abstract

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Replimune Provides Update on RP1 Clinical Development Program in Cutaneous Squamous Cell Carcinoma

Replimune Group Inc. announced that the first patient has been enrolled in its registration-directed, randomized, controlled Phase II clinical trial of RP1 in combination with Regeneron and Sanofi’s Libtayo^® (cemiplimab-rwlc) compared to Libtayo alone in patients with cutaneous squamous cell carcinoma. [Replimune Group, Inc.] Press Release

Foamix Announces FDA Acceptance of Its New Drug Application for FMX103 Minocycline Foam for the Treatment of Moderate-to-Severe Papulopustular Rosacea

Foamix Pharmaceuticals Limited announced that the FDA has accepted for review the New Drug Application for FMX103 (minocycline topical foam 1.5%) topical foam. Foamix is seeking approval of FMX103 for the treatment of moderate-to-severe papulopustular rosacea in adults. The FDA has set June 2nd, 2020 as the Prescription Drug User Fee Act action date. [Foamix Pharmaceuticals Limited] Press Release

$3 Billion Ballot Proposition Will Decide Fate of Texas Cancer Research Funding Agency

On 5 November, Texas residents will decide whether to sustain CPRIT, the second largest public source of cancer funding in the United States after the federal government. At stake is its generous support for 123 tenure-track faculty like Cole, who investigates cancer and DNA repair. [ScienceMagazine] Editorial

Indian Government Tightens Rules on Academic Collaboration with China

India is tightening the rules for academic collaborations with its neighbor and main rival, China. Under a new policy, universities and research institutes must seek permission from the ministries of Home Affairs and External Affairs before signing a collaboration agreement or memorandum of understanding with a Chinese institution. [ScienceMagazine] Editorial

NEW Tissue Engineering and Regenerative Medicine International Society (TERMIS) European Chapter Meeting 2020
May 26-29, 2020
Manchester, United Kingdom

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NEW Research Coordinator – Dermatology and Venereology (Karolinska Institutet)

NEW Postdoctoral Fellowship – DNA Damage Repair Pathways in Melanoma Prevention (University of Southern California)

NEW Postdoctoral Training Fellow – Evolutionary Biology in Renal Cancer and Melanoma (The Francis Crick Institute)

NEW Medical Science Liaison – Dermatology (Eli Lilly and Company)

Assistant Professor – Biochemistry (University of Washington)

Postdoctoral Studies – Bioinformatics to Understand T Cell Biology (Karolinska Institutet)

Postdoctoral Fellowship – Dermatology (Brigham and Women’s Hospital)

Postdoctoral Fellowship – Wound Healing and Tissue Regeneration (Memorial Sloan Kettering Cancer Center)

Faculty Positions – Cutaneous Oncology and Skin Cancer Research (Columbia University Medical Center)

Postdoctoral Researcher – Cancer Research (Champalimaud Foundation)

Postdoctoral Position – Cancer Immunology (Northwestern University Feinberg School of Medicine)

Faculty Position – Cancer Biology (Children’s Research Institute at UT Southwestern)

Faculty Position – Cancer Biology (Emory University)

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