Dermal Cell News Volume 5.00 | Jan 7 2019

TOP STORY

UC San Diego Researchers Identify How Skin Ages, Loses Fat and Immunity

Researchers showed how fibroblasts developed into fat cells and identified the pathway that caused this process to cease as people aged. [Press release from University of California, San Diego discussing online prepublication in Immunity] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

STIM1 Thermosensitivity Defines the Optimal Preference Temperature for Warm Sensation in Mice

Scientists showed that STIM1, an endoplasmic reticulum (ER) resident transmembrane protein that responded to both ER Ca²⁺ depletion and heat, mediated temperature-induced Ca²⁺ influx in skin keratinocytes via coupling to Orai Ca²⁺ channels in plasma membrane. [Cell Res] Abstract

A Novel Form of JARID2 Is Required for Differentiation in Lineage-Committed Cells

JARID2 knockout in keratinocytes resulted in up-regulation of cell cycle genes and repression of many epidermal differentiation genes. [EMBO J] Full Article | Graphical Abstract

Dermal Condensate Niche Fate Specification Occurs Prior to Formation and Is Placode Progenitor Dependent

Co-expression of downregulated fibroblast and upregulated dermal condensate genes in niche precursors revealed a transitory molecular state following a proliferation shutdown. [Dev Cell] Abstract | Graphical Abstract

Single-Cell Analysis Reveals a Hair Follicle Dermal Niche Molecular Differentiation Trajectory That Begins Prior to Morphogenesis

Using unbiased single-cell RNA sequencing and in vivo methods, scientists inferred a sequence of transcriptional states through which dermal condensate cells passed that began prior to hair follicle morphogenesis. [Dev Cell] Abstract | Graphical Abstract

Lysyl Oxidase Enzymes Mediate TGF-β1-Induced Fibrotic Phenotypes in Human Skin-Like Tissues

Inhibition of specific lysyl oxidases (LOX) isoforms, LOX and LOXL4, in foreskin fibroblasts resulted in antagonistic effects on TGF-β1-induced fibrogenic hallmarks in both human skin equivalents and self-assembled stromal tissues. [Lab Invest] Abstract

SKIN CANCERS & DISORDERS

Loss of Phd2 Cooperates with BRAF^V600E to Drive Melanomagenesis

Deletion of Phd2 in combination with expression of BRaf^V600E in melanocytes led to the development of melanoma with 100% penetrance and frequent lymph node metastasis. [Nat Commun] Full Article

Dual Inhibition of MDM2 and MDM4 in Virus-Positive Merkel Cell Carcinoma Enhances the p53 Response

Investigators observed that depletion of EP400 in Merkel cell polyomavirus-positive Merkel cell carcinoma cell lines led to increased p53 target gene expression. [Proc Natl Acad Sci USA] Abstract

Dysfunctional Autophagy Induced by the Pro-Apoptotic Natural Compound Climacostol in Tumor Cells

In B16-F10 mouse melanomas climacostol exerted a marked and sustained accumulation of autophagosomes as the result of dysfunctional autophagic degradation. [Cell Death Dis] Full Article

Combination Therapy Targeting the Elevated Interleukin-6 Level Reduces Invasive Migration of BRAF Inhibitor-Resistant Melanoma Cells

Scientists confirmed the development of BRAF inhibitor (BRAFi) resistance in BRAFi-treated melanoma cell lines by demonstrating reduced sensitivity to BRAF inhibitors, increased ERK1/2 activity and increased WNT5A expression. [Mol Oncol] Full Article | Abstract

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Advanced Drug Delivery Systems and Artificial Skin Grafts for Skin Wound Healing

The authors cover comprehensively the advanced treatment strategies to improve the quality of wound healing. [Adv Drug Deliv Rev] Abstract | Graphical Abstract

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Pulse Biosciences Announces Positive Clinical Results of Its Nano-Pulse Stimulation™ Technology Platform to Treat Patients with Sebaceous Hyperplasia Lesions on the Face

Pulse Biosciences, Inc. announced positive results from its clinical efficacy study using proprietary Nano-Pulse Stimulation™ technology to treat patients with Sebaceous Hyperplasia, a difficult-to-treat skin condition that typically presents on the face. [Pulse Biosciences, Inc. (Business Wire, Inc.)] Press Release

Pfizer Initiates Phase IIB/III Clinical Trial for PF-06651600, an Oral JAK3 Inhibitor, for the Treatment of Patients with Moderate to Severe Alopecia Areata

Pfizer Inc. announced the initiation of a Phase IIb/III clinical trial for its oral JAK3 inhibitor, PF-06651600, for the treatment of patients with moderate to severe alopecia areata, a chronic autoimmune skin disease that causes hair loss on the scalp, face, or body, and currently has no approved therapies. [Pfizer, Inc.] Press Release

Merck’s KEYTRUDA^® (Pembrolizumab) Receives Five New Approvals in Japan, Including in Advanced Non-Small Cell Lung Cancer, as Adjuvant Therapy for Melanoma, and in Advanced Microsatellite Instability-High Tumors

Merck announced that KEYTRUDA, Merck’s anti-PD-1 therapy, simultaneously received five new approvals from the Japan Pharmaceuticals and Medical Devices Agency, including three expanded uses in advanced non-small lung cancer, one in melanoma, as well as a new indication in advanced microsatellite instability-high tumors. [Merck & Co., Inc.] Press Release

Incyte Announces First Patient Treated in Phase III Clinical Trial Program for Ruxolitinib Cream in Atopic Dermatitis

Incyte announced that the first patient was treated in the Phase III TRuE-AD clinical trial program evaluating the long-term safety and efficacy of ruxolitinib cream as monotherapy for adolescent and adult patients with atopic dermatitis who were candidates for topical therapy. [Incyte Corporation] Press Release

Asana BioSciences Announces Initiation of First-in-Human Clinical Study with ASN008, a Novel Topical Product for the Treatment of Pruritus Associated with Atopic Dermatitis

Asana BioSciences announced that it has been granted permission by the FDA to start human clinical trials with ASN008, a topical gel for the treatment of pruritus (itch) associated with atopic dermatitis. [Asana BioSciences, LLC] Press Release

FDA Approves Merck’s KEYTRUDA® (Pembrolizumab) for the Treatment of Adult and Pediatric Patients with Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma, a Rare Form of Skin Cancer

Merck announced that the FDA has approved KEYTRUDA, Merck’s anti-PD-1 therapy, for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma, based on the results of the Cancer Immunotherapy Trials Network’s CITN-09/KEYNOTE-017 trial. [Merck & Co., Inc.] Press Release

Donald Trump Finally Has a White House Science Adviser

Nearly two years after he took office, US President Donald Trump has a White House science adviser in place. The Senate confirmed meteorologist Kelvin Droegemeier for the job in a voice vote on 2 January. [Nature News] Editorial

Scientists Despair as US Government Shutdown Drags On

As the shutdown hits the two-week mark with no end in sight, its effects on science have begun to compound, leaving many government researchers weary, worried and demoralized. [Nature News] Editorial

UK Universities Warn ‘No Deal’ Brexit Will Hit Crucial Funding Streams

UK universities have warned the country’s government that leaving the European Union without a deal is “one of the biggest threats” the institutions have ever faced. [Nature News] Editorial

NEW Keystone Symposia: Skin Health & Disease – Immune, Epithelial & Microbiome Crosstalk
April 8-11, 2019
Hannover, Germany

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NEW Postdoctoral Associate – Pathology (Stony Brook University)

NEW PhD Studentship – Melanoma (University of Otago)

NEW Research Fellow – Stem Cell Biology (Brigham & Women’s Hospital)

NEW Postdoctoral Position – Pluripotent Stem Cells (I-STEM)

Professor – Dermatological Oncology (University of Tubingen)

Grant Program – Skin Disease Research (Brigham & Women’s Hospital and Harvard Medical School)

Assistant Professor of Pediatrics – Dermatology (Harvard Medical School)

Tenure Faculty – Cancer Biology (University of Chicago)

Assistant Professor – Cancer Biology (University of Pennsylvania)

Postdoctoral Researcher – Skin Epithelial Stem Cells (University of Michigan)

Senior Researcher – Skin Biology (University of Pennsylvania)

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