Dermal Cell News Volume 4.17 | May 14 2018

TOP STORY

An Acquired Vulnerability of Drug-Resistant Melanoma with Therapeutic Potential

Investigators found that resistance to BRAF+MEK inhibitors is associated with increased levels of reactive oxygen species (ROS). Subsequent treatment with the histone deacetylase inhibitor vorinostat suppressed SLC7A11, leading to a lethal increase in the already-elevated levels of ROS in drug-resistant cells. [Cell] Abstract | Graphical Abstract | Press Release

(Ranked by impact factor of the journal)

DERMAL STEM CELLS & TISSUE REGENERATION

Identifying Novel Strategies for Treating Human Hair Loss Disorders: Cyclosporine A Suppresses the Wnt Inhibitor, SFRP1, in the Dermal Papilla of Human Scalp Hair Follicles

Scientists found that secreted frizzled related protein 1 (SFRP1) regulates intrafollicular canonical Wnt/β-catenin activity through inhibition of Wnt ligands in the human hair bulb. Inhibiting SFRP1 activity through the SFRP1 antagonist, WAY-316606, enhanced hair shaft production, hair shaft keratin expression, and inhibited spontaneous hair follicle regression (catagen) ex vivo. [PLoS Biol] Full Article | Press Release

Molecular Functional Analyses Revealed Essential Roles of HSP90 and Lamin A/C in Growth, Migration, and Self-Aggregation of Dermal Papilla Cells

Investigators revealed that dermal papilla cells transfected with siHSP90 and siLamin A/C had defective cell proliferation and growth, prolonged doubling time, cell cycle arrest at G0/G1 phase, and defective self-aggregation formation. [Cell Death Discov] Full Article

Mouse Keratinocytes without Keratin Intermediate Filaments Demonstrate Substrate Stiffness Dependent Behaviors

The absence of keratin intermediate filaments (IFs) affected cell morphology, spread area, and cytoskeleton and adhesion protein organization on both soft and stiff substrates. Strikingly, an absence of keratin IFs also significantly reduced the ability of mouse keratinocytes to mechanically deform the soft substrate. [Cell Mol Bioeng] Abstract

SKIN CANCERS & DISORDERS

Humidity-Regulated CLCA2 Protects the Epidermis from Hyperosmotic Stress

The epidermis of patients with atopic dermititis, organotypic skin cultures under dry conditions, and cultured keratinocytes exposed to hyperosmotic stress showed up-regulation of the nonorthologous human homolog CLCA2. Hyperosmolarity-induced CLCA2 expression occurred via p38/c-Jun N-terminal kinase–activating transcription factor 2 signaling. [Sci Transl Med] Abstract

STXBP4 Regulates APC/C-Mediated p63 Turnover and Drives Squamous Cell Carcinogenesis

Scientists demonstrated that the anaphase-promoting complex/cyclosome (APC/C) complex plays an essential role in the ubiquitin-mediated turnover of N-terminally truncated isoform of p63 (ΔNp63α) through the M-G1 phase. In addition, syntaxin-binding protein 4 (Stxbp4), previously discovered to bind to ΔNp63, suppressed the APC/C-mediated proteolysis of ΔNp63. [Proc Natl Acad Sci USA] Abstract

NRP-1 Interacts with GIPC1 and α6/β4-Integrins to Increase YAP1/∆Np63α-Dependent Epidermal Cancer Stem Cell Survival

Researchers showed that neuropilin-1 (NRP-1) formed a complex with GIPC1 and α6/β4-integrin to activate FAK/Src signaling, which lead to stabilization of YAP1/∆Np63α and enhanced epidermal cancer stem cell survival, invasion, and angiogenesis. Loss of NRP-1, GIPC1, α6/β4-integrins, YAP1, or ∆Np63α reduced these responses. [Oncogene] Abstract

E2F1 Inhibition Mediates Cell Death of Metastatic Melanoma

The authors confirmed that E2F1 is highly expressed in melanoma cells. Inhibition of E2F1 activity further increased melanoma cell death and senescence, both in vitro and in vivo. Moreover, blocking E2F1 also induced death of melanoma cells resistant to BRAF inhibitors. [Cell Death Dis] Full Article

MicroRNA-17-92 Cluster Promotes the Proliferation and the Chemokine Production of Keratinocytes: Implication for the Pathogenesis of Psoriasis

Investigators found that miR-17-92 cluster promoted the proliferation and the cell-cycle progression of keratinocytes via suppressing cyclin-dependent kinase inhibitor 2B. Increased expression of miR-17-92 cluster was detected in psoriatic lesions and the level of lesional miR-17-92 cluster was positively correlated with the disease severity in psoriasis patients. [Cell Death Dis] Full Article

Combination of Anti-vascular Agent – DMXAA and HIF-1α Inhibitor – Digoxin Inhibits the Growth of Melanoma Tumors

Scientists investigated the inhibition of murine melanoma growth by combining two agents: anti-vascular – DMXAA and the HIF-1α inhibitor – digoxin and explained the mechanism of action of this combination. After DMXAA treatment tumor size was reduced only for a limited time. After seven days regrowth of tumors was observed and number of vessels was increased especially in the tumor’s peripheral areas. [Sci Rep] Full Article

The Unique Molecular Signatures of Contact Dermatitis and Implications for Treatment

Allergic contact dermatitis (ACD) in the setting of concurrent atopic dermititis (AD) shows a different and attenuated phenotype as compared to healthy individuals with ACD, which influences the way AD patients respond to vaccination and other treatment modalities. As in contact sensitization, skin challenged by food patch testing shows that common food allergens (e.g., peanut and barley) also cause distinct immune polarizations in the skin. [Clin Rev Allergy Immunol] Abstract

New Insights into the Roles of Myofibroblasts and Innervation during Skin Healing and Innovative Therapies to Improve Scar Innervation

The authors discuss the mechanisms leading to normal or excessive scarring and present the roles of innervation during wound healing. Advantages and limitations in the use of neuropeptides, growth factors and biomaterials are discussed as well as the most recent studies on electrostimulation and the potential of targeting resident skin mesenchymal stem cells. [Exp Dermatol] Abstract | Full Article

Visit our reviews page to see a complete list of reviews in the dermal cell research field.

Asana BioSciences to Present Positive Clinical Efficacy and Skin Biomarker Data in Atopic Dermatitis Patients Treated with Its Novel Oral JAK/SYK Inhibitor, ASN002

Asana BioSciences, announced that it will present efficacy and biomarker data from the clinical proof of concept study with ASN002, an oral, once-daily dual JAK/SYK inhibitor, in patients with moderate-to-severe atopic dermatitis. [Press release from Asana BioSciences, LLC discussing research to be presented at the International Eczema Council (IEC) meeting and the International Investigative Dermatology (IID) meeting, Orlando] Press Release

New Grants Totaling $2.6 Million Fund Work to Reduce Immunotherapy Side Effects

As the world marks Melanoma Awareness Month, the American Cancer Society and the Melanoma Research Alliance selected the first group of scientists to receive newly established research grants to investigate how to reduce rare, but serious, side effects resulting from cancer treatments with checkpoint inhibitors, a type of immunotherapy. [Melanoma Research Alliance] Press Release

Galapagos and MorphoSys Announce Initiation of the IGUANA Phase II Clinical Trial with MOR106 in Atopic Dermatitis Patients

MorphoSys AG and Galapagos NV announced that the first patient has been enrolled in IGUANA, a Phase II study with MOR106, an investigational antibody directed against IL-17C, in atopic dermatitis patients. [MorphoSys AG] Press Release

FDA Seeks Permanent Injunctions against Two Stem Cell Clinics

The FDA, in two complaints filed in federal court, is seeking permanent injunctions to stop two stem cell clinics from marketing stem cell products without FDA approval and for significant deviations from current good manufacturing practice requirements. [U.S. Food and Drug Administration] Press Release

Hungarian Scientists Are on Edge As Country Is Poised to Force Out Top University

In early April, several days after Viktor Orbán secured his third consecutive term—and fourth overall—as Hungarian prime minister with a landslide victory for his conservative party, the pro-government paper Figyelő; published a list of more than 200 people it called “mercenaries” of George Soros, the American-Hungarian billionaire philanthropist. The list included investigative journalists and human rights advocates—and 30 academics from the Soros-founded, Budapest-based Central European University. [ScienceInsider] Editorial

Release of Three Americans by North Korea Bolsters Hopes for Academic Diplomacy

The release of three Americans by North Korea is being welcomed in the United States. Leaders of the Pyongyang University of Science and Technology in North Korea also see the move as good news, and are hoping it might ultimately lead to the end of a travel ban that has prevented its U.S. instructors from teaching classes. [ScienceInsider] Editorial

Harassment Should Count as Scientific Misconduct

Research culture and policies are quick to denounce plagiarism, data fabrication and mismanagement of funds, yet we have too long ignored the mistreatment of people. Science is a social endeavor; ignoring harassment perpetuates a culture in which people who experience or witness hostile behaviors are afraid to speak up, cannot do their best work, or leave science altogether. [Nature News] Editorial

NEW 14^th European Association of Dermato-Oncology (EADO) Congress
November 6-9, 2018
Barcelona, Spain

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Fellow – Skin Stem Cells & Wound Healing (Johns Hopkins University)

NEW Postdoctoral Fellow – Cancer Signaling & Trascription (The Francis Crick Institute)

Postdoctoral Position – Melanoma Tumor Inflammation & Immune Tolerance (University of Colorado)

Associate Professor or Professor – Skin Cancer (The University of Texas M.D. Anderson Cancer Center)

Postdoctoral Fellow – Psoriasis Research (Case Western Reserve University)

Postdoctoral Fellow – Skin Cancer Biology (UT Southwestern Medical Center)

Postdoctoral/Research Scientist – Cancer Metabolism (Wake Forest Comprehensive Cancer Center)

Postdoctoral Fellow – Skin Cancer Research (University of Pennsylvania)

Postdoctoral Researcher – Melanoma (Ghent University)

Faculty Position – Developmental Biology and Regenerative Medicine (Seattle Children’s Research Institute)

PhD or Postdoctoral Position – Tissue Repair, Stem Cell Fate and Tumor Heterogeneity (Université Libre de Bruxelles)

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