Barbara Gilchrest

• Harvard University

We report the synthesis and application of an elastic, wearable crosslinked polymer layer (XPL) that mimics the properties of normal, youthful skin. XPL is made of a tunable polysiloxane-based material that can be engineered with specific elasticity, contractility, adhesion, tensile strength and occlusivity. XPL can be topically applied, rapidly cu...

The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.

The Journal of Investigative Dermatology Symposium Proceedings publishes basic and clinical research in cutaneous biology and skin disease.

The Journal of Investigative Dermatology Symposium Proceedings publishes basic and clinical research in cutaneous biology and skin disease.

The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.

The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.

Background: Photodynamic therapy (PDT) using aminolevulinic acid (ALA) with blue light or red light is effective for treating actinic keratoses (AKs). However, immunosuppression follows red light PDT, raising the spectre of skin cancer promotion in treated skin. Objective: To determine whether broad-area short incubation (BASI)-ALA-PDT using blu...

Background Many therapeutic options are available for treating keloids, but success rates vary widely, and the keloids often recur. The Food and Drug Administration has recently approved intralesional collagenase for the treatment of Dupuytren's contracture. This medication has not been explored for the treatment of earlobe keloids, a common proble...

The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.

The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.

The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.

Abbreviations: ANOVA, analysis of variance; BCC, basal cell carcinoma; CPD, cyclobutane pyramidine dimer; KO, knockout; pTT, thymidine dinucleotide; PG/DMSO, propylene glycol 75%/DMSO 25%; SCC, squamous cell carcinoma; T-oligo, telomere homolog oligonucleotide

Pagetoid reticulosis or Woringer-Kolopp disease (WKD) is a rare variant of mycosis fungoides, consisting of localized patches or plaques containing intraepidermal proliferations of neoplastic T cells in a pagetoid distribution (similar to that of the adenocarcinomatous cells found in Paget disease of the nipple), which typically affects middle-aged...

No one can argue about the merit of evidence-based medicine. Rigorously quantifying the safety and efficacy of the medications and devices used to treat our patients allows for well-informed decisions and allocation of limited resources. This is as true for dermatology as for other medical and surgical disciplines. Evidence-based medicine promises...

Acute primary cutaneous leishmaniasis typically presents microscopically with a lymphohistiocytic infiltrate containing admixed plasma cells, parasitized macrophages and abundant organisms. Tuberculoid granulomatous changes may occur in the later phases of primary infection. A 23-year-old male presented 1 month after visiting Peru with classic clin...

"Vitamin D" is the term commonly used to denote the lipid-soluble hormone critical for calcium homeostasis and skeletal maintenance. A precursor to the active compound is found in many plants and animal tissues and can be absorbed from the gut; it can also be derived from cell membranes in the epidermis during ultraviolet B irradiation. This compou...

Cutaneous biopsies often heal with little or no scarring. Prior studies have shown an alarming percentage of patients who incorrectly identify biopsy sites at the time of surgery. To investigate the safety and utility of an ultraviolet (UV)-fluorescent tattoo for biopsy site identification. A preclinical proof of concept was established with skin c...

Ultraviolet (UV) radiation is an established carcinogen that causes skin cancers and other cutaneous photodamage. Vitamin D is produced in the skin after UV exposure and may also be obtained from dietary and supplemental sources. The effect of recommendations for UV protection, as well as for very large vitamin D supplements, and possible adverse e...

Identification, prevention and reversal of age-related changes in the appearance and function of human skin remain goals of great interest to scientists, dermatologists and patients. In recent decades, the cellular and molecular changes that underlie cutaneous aging have been substantially elucidated. These data suggest that cutaneous aging, like a...

In the face of increasing evidence that indoor tanning is harmful, tanning enthusiasts and the tanning industry defend the practice on several grounds. The principal argument offered in defense of year-round tanning is the claimed health benefit of high levels of vitamin D, also called the sunshine vitamin, which is made in skin following UV irradi...

Photoaging comprises the adverse effects of chronic ultraviolet radiation (UVR) on the skin, superimposed on the intrinsic aging process [1]. The magnitude of the problem of photoaging is large and expanding [2] as a result of factors such as increasing ultraviolet exposure from ozone layer depletion, increasing popularity of tanning salons, and “s...

The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.

Ionizing radiation (IR) is a widely used approach to cancer therapy, ranking second only to surgery in rate of utilization. Responses of cancer patients to radiotherapy depend in part on the intrinsic radiosensitivity of the tumor cells. Thus, promoting tumor cell sensitivity to IR could significantly enhance the treatment outcome and quality of li...

The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.

Telomere homolog oligonucleotides (T-oligos) activate an innate telomere-based program that leads to multiple anticancer effects. T-oligos act at telomeres to initiate signaling through the Werner protein and ATM kinase. We wanted to determine if T-oligos have antiangiogenic effects. We found that T-oligo-treated human melanoma (MM-AN) cells had de...

Reactive oxygen species (ROS) are generated by cellular metabolism as well as by exogenous agents. While ROS can promote cellular senescence, they can also act as signaling molecules for processes that do not lead to senescence. Telomere homolog oligonucleotides (T-oligos) induce adaptive DNA damage responses including increased DNA repair capacity...

UV-induced melanogenesis (tanning) and "premature aging" or photoaging result in large part from DNA damage. This article reviews data tying both phenomena to telomere-based DNA damage signaling and develops a conceptual framework in which both responses may be understood as cancer-avoidance protective mechanisms.Journal of Investigative Dermatolog...

DUSA Pharmaceuticals donated the Kerasticks and the light source for this study.

Retinoids are a group of naturally occurring and synthetic compounds with vitamin A-like biological activity. They play an important role in vision, reproduction, growth, and epithelial cell differentiation. Recent discoveries of specific retinoid cellular binding proteins and nuclear receptors have led to a better (although not complete) understan...

Conventional cancer therapeutics target rapidly proliferating cells by introducing widespread damage into DNA, but do so nonselectively, damaging normal as well as malignant cells. As a result, maximally tolerated doses are often not curative and the treatment regimens are often highly toxic. In recent years targeted "smart therapies" have been dev...

The major differentiated function of melanocytes is the synthesis of melanin, a pigmented heteropolymer that is synthesized in specialized cellular organelles termed melanosomes. Mature melanosomes are transferred to neighboring keratinocytes and are arranged in a supranuclear cap, protecting the DNA against incident ultraviolet light (UV) irradiat...

Human B- or T-cell lymphoma lines and primary murine lymphomas were treated with DNA oligonucleotides homologous to the telomere (TTAGGG repeat; "T-oligo"), either alone or in combination with standard, widely-used anticancer chemotherapeutic agents. T-oligo induces cell cycle arrest and apoptosis in cultured human or murine B or T-lymphoma cell li...

Bone Morphogenetic Protein (BMP-4) was shown to down-regulate melanogenesis, in part, by decreasing the level of tyrosinase [Yaar et al. (2006) JBC:281]. Results presented here show that BMP-4 down-regulated the protein levels of TRP-1, PKC-beta, and MCI-R. When paired cultures of human melanocytes were treated with vehicle or BMP-4 (25 ng/ml), MAP...

Amyloid beta (Abeta) was shown to bind the 75 kD neurotrophin receptor (p75(NTR)) to induce neuronal death. We synthesized a p75(NTR) antagonistic peptide (CATDIKGAEC) that contains the KGA motif that is present in the toxic part of Abeta and closely resembles the binding site of NGF for p75(NTR). In vivo injections of Abeta into the cerebral corte...

Ultraviolet radiation is a carcinogen that also compromises skin appearance and function. Because the ultraviolet action spectra for DNA damage, skin cancer, and vitamin D(3) photosynthesis are identical and vitamin D is readily available from oral supplements, why has sun protection become controversial? First, the media and, apparently, some rese...

The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.

Ultraviolet (UV) radiation is a carcinogen that also compromises skin appearance and function. Since the UV action spectra for DNA damage, skin cancer, and vitamin D photosynthesis are identical, and vitamin D is readily available from oral supplements, why has sun protection become controversial? First, the media and, apparently, some researchers...

Treatment with thymidine dinucleotide (pTT) has well documented DNA-protective effects and reduces development of squamous cell carcinoma in UV-irradiated mice. The preventive effect of pTT on basal cell carcinoma (BCC) was evaluated in UV-irradiated Ptch-1(+/-) mice, a model of the human disease Gorlin syndrome. Topical pTT treatment significantly...

Human skin has developed elaborate defense mechanisms for combating a wide variety of potentially damaging environmental factors; principal among these is UV light. Despite these defenses, short-term damage may include painful sunburn and long-term UV damage results in both accelerated skin aging and skin cancers such as basal cell carcinoma, squam...

Photoageing is the superposition of chronic ultraviolet (UV)-induced damage on intrinsic ageing and accounts for most age-associated changes in skin appearance. It is triggered by receptor-initiated signalling, mitochondrial damage, protein oxidation and telomere-based DNA damage responses. Photodamaged skin displays variable epidermal thickness, d...

To document and quantify inducible photoprotective effects in human skin, explant cultures were treated once with thymidine dinucleotide (pTT) or diluent alone or UV-irradiated. Both pTT and UV increased the melanogenic protein levels on days 1-5 and comparably increased melanocyte dendricity and epidermal melanin content. Explants treated with pTT...

The current study determined the ability of a p75(NTR) antagonistic cyclic peptide to rescue cells from beta amyloid (Abeta) (1-40)-induced death. p75(NTR)-, p140(trkA)-NIH-3T3 cells or E17 foetal rat cortical neurones were incubated with 125I-NGF or 125I-Abeta (1-40) and increasing concentrations of the cyclic peptide (CATDIKGAEC). Peptide ability...

Telomere 3' overhang-specific DNA oligonucleotides (T-oligos) induce cell death in cancer cells, presumably by mimicking telomere loop disruption. Therefore, T-oligos are considered an exciting new therapeutic strategy. The purpose of this study was to elucidate how T-oligos exert antitumor effects on human malignant glioma cells in vitro and in vi...

It was previously reported that telomere homologue oligonucleotides (T-oligos) can induce a variety of cellular responses in skin including increased melanogenesis. To assess the effects of T-oligos on hair pigmentation, we administered thymidine dinucleotide (pTT), one-third of the TTAGGG telomere repeat sequence, intradermally at distinct time po...

To assess the total number, recruitment rate, departure rate, and growth rate of full-time academic dermatologists in the United States over the last decade. Mail survey. Academic dermatology departments in the United States. Respondents among 113 chairs or chiefs of academic dermatology departments or their designees. The total number of full-time...

Ultraviolet (UV) radiation is a proven carcinogen, responsible for more than half of all human malignancies. It also compromises skin appearance and function. Since the UV action spectra for DNA damage, skin cancer and Vitamin D(3) (vit D) photosynthesis are identical and vit D is readily available from oral supplements, why has sun protection beco...

Cancer is the second leading cause of death in the USA, with metastatic disease proving a particular management challenge. Treatment modalities for patients with metastatic disease are limited, and survival beyond 5 years is uncommon. We have reported that an 11-base DNA oligonucleotide 100% homologous to the telomere 3' overhang can induce apoptos...

Cancer is a leading cause of death in Americans. We have identified an inducible cancer avoidance mechanism in cells that reduces mutation rate, reduces and delays carcinogenesis after carcinogen exposure, and induces apoptosis and/or senescence of already transformed cells by simultaneously activating multiple overlapping and redundant DNA damage...

To evaluate the cost-effectiveness of various melanoma screening strategies proposed in the United States. We developed a computer simulation Markov model to evaluate alternative melanoma screening strategies. Hypothetical cohort of the general population and siblings of patients with melanoma. Intervention We considered the following 4 strategies:...

Telomeres cap the ends of eukaryotic chromosomes and prevent them from being recognized as DNA breaks. We have shown that certain DNA damage responses induced during senescence and, at times of telomere uncapping, also can be induced by treatment of cells with small DNA oligonucleotides homologous to the telomere 3′ single-strand overhang (T-oligos...

We have shown that DNA oligonucleotides substantially homologous to the telomere 3-prime overhang sequence (T-oligos) increase DNA repair capacity (DRC) in cultured human cells and decrease UV-induced mutation rate and photocarcinogenesis in mouse skin. To investigate the protective effects of T-oligos in intact human skin, paired skin explants obt...

Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta family, signal in many cells including neural precursors. Two receptors, types 1 and 2, coordinately mediate BMP signaling, and type 1 receptor has two forms: A and B. Using RT-PCR we found that neural crest-derived human melanocytes express BMP receptor-1A, -1B, and...

Identifying high-risk individuals for melanoma education and risk reduction may be a viable strategy to curb the incidence of melanoma, which has risen precipitously in the past 50 years. The first-degree relatives of melanoma patients represent a risk group who may experience a 'teachable moment' for enhanced education and risk reduction. We repor...

Examination of the skin or hair with Wood's lamp has long been used to aid in the clinical diagnosis of some cutaneous disorders. A new observation reported here illustrates that Wood's light can be used to determine the depth of melanin pigmentation in the skin: contrast in epidermal pigmentation is increased while contrast in dermal pigmentation...

The cAMP-dependent pathway up-regulates MITF (microphthalmia-associated transcription factor), important for key melanogenic proteins such as tyrosinase, TRP-1 (tyrosinase-related protein 1) and TRP-2. We asked whether MITF is also a key transcription factor for PKC-beta (protein kinase C-beta), required to phosphorylate otherwise inactive tyrosina...

To determine physician preparation for performing the skin cancer examination (SCE). We evaluated medical students' observation, training, and practice of the SCE; hours spent in a dermatology clinic; and self-reported skill level for the SCE by a self-administered survey. Graduating students at 7 US medical schools during the 2002-2003 academic ye...

The United States is now faced with a mounting public health problem of high and increasing incidence and mortality rates for melanoma, particularly among men who are middle-aged or older.1,2 Melanoma is a serious and often fatal form of skin cancer, even though most melanomas are readily visible when they are still thin and nearly always curable b...

Early detection and excision of skin cancers has the potential to significantly improve health outcomes.1,2 Unfortunately, few primary care physicians perform skin cancer screening routinely. Inadequate training and low confidence in their ability to recognize skin cancer are potential barriers.3 Educating all physicians regarding skin cancer detec...

IntroductionMechanisms of AgingSkin AgingInfections/InfestationsInflammatory DisordersBenign NeoplasmsPremalignant and Malignant NeoplasmsCutaneous Manifestations of Internal MalignancyKey ReferencesReferences

UV radiation is a well-documented human carcinogen, indisputably linked to the current continued increased rate of skin cancer. UV radiation is also responsible for cutaneous synthesis of vitamin (vit) D3, a substance that is then sequentially hydroxylated in the liver and kidney to yield 1,25(OH)2 vit D, a hormone critical for calcium homeostasis...

Estrogens have a profound influence on skin. The relative hypoestrogenism that accompanies menopause exacerbates the deleterious effects of both intrinsic and environmental aging. Estrogens clearly have a key role in skin aging homeostasis as evidenced by the accelerated decline in skin appearance seen in the perimenopausal years. Estrogens improve...

In vivo reflectance confocal microscopy (RCM) provides high-resolution optical sections of the skin in its native state, without needing to fix or section the tissue. Melanin provides an excellent contrast for RCM, giving a bright signal in the confocal images. The pigmented guinea-pig is a common animal model to study human pigment induction and m...

Ethnic differences in skin properties has attracted great interest in the past, but apart from the visible differences in pigmentation, their assessment has frequently yielded indefinite or conflicting results. Whereas it is self-evident that skin aging affects all human beings regardless of their ethnic background, it is commonly assumed that diff...

The population is aging at a rapid rate, and with the baby boomer generation at the geriatric doorstep the trend is set to continue in the next 50 years. The elderly are affected by many dermatological concerns, which are not only caused by the normal aging process. Moreover, these concerns are related to additional lifelong exposure to environment...

For decades it has been appreciated that aging is a consequence of both genetic and environmental influences. Genetic factors are evident, for example, in the > 100-fold variation among species in the rate of aging; and recent studies of fruit flies, worms and even mice have identified specific longevity genes whose modification can greatly alter l...

The topic of skin aging is of growing importance to all working in the field of dermatology, aesthetic medicine and cosmetic medicine. Two internationally well-known and leading experts in the field present a comprehensive state-of-the-art review on all aspects of skin aging. With its clear, concise and reader-friendly format this book has all the...

Work in many laboratories over the past decade has established a central role for the telomere in maintaining genomic integrity. Available data may be interpreted to indicate that telomere disruption, whether due to acute DNA damage or progressive telomere shortening, is the initial event that triggers multiple DNA damage responses. The specific in...

Many older individuals use products and procedures to conceal or delay the signs of aging. For most, this provides a helpful ego boost, but some suffer from pathologies such as eating disorders and body dysmorphic disorder. The impact of aging skin may include social anxiety and social isolation. Poor self-image is associated with chronic illness a...

Chronically irradiated murine skin and UV light-induced squamous cell carcinomas overexpress the inducible isoform of cyclooxygenase (COX-2), and COX-2 inhibition reduces photocarcinogenesis in mice. We have reported previously that DNA oligonucleotides substantially homologous to the telomere 3'-overhang (T-oligos) induce DNA repair capacity and m...

Vascular endothelial growth factor (VEGF) is constitutively produced by keratinocytes, but has no known epidermal target cell. We now report that normal human melanocytes (Mc) maintained in serum-free, hormone-, and growth factor-supplemented medium lacking phorbol ester and choleragen constitutively express VEGF receptor-1 (VEGFR-1), VEGFR-2, and...

Hair pigmentation is controlled by tightly coordinated programs of melanin synthesis and involves signaling through the melanocortin type 1 receptor (MC-1R) that regulates the switch between pheomelanogenesis and eumelanogenesis. However, the involvement of other signaling systems, including the bone morphogenetic protein (BMP) pathway, in the cont...

Cellular senescence is a major defense against cancer. In human fibroblasts, suppressing both the p53 and pRb pathways is necessary to bypass replicative senescence as well as senescence induced by ectopic expression of a dominant negative form of the telomere repeat binding factor 2, TRF2(DN). We recently reported that exposure to oligonucleotides...

Chemotherapeutic agents induce p53-dependent apoptosis in the hair follicle (HF) resulting in hair loss, a common side effect of cancer therapy. Here, we show that Fas as a p53 target plays important role in the HF response to cyclophosphamide. Specifically, we demonstrate that Fas is up-regulated in HF keratinocytes after cyclophosphamide treatmen...

Melanoma is the most fatal skin cancer, often highly resistant to chemotherapy. Here we show that treatment with an 11-base DNA oligonucleotide homologous to the telomere 3' overhang sequence (T-oligo) induces apoptosis of several established human melanoma cell lines, including the aggressive MM-AN line, whereas normal human melanocytes exposed to...

In this study, we investigated the effects of estradiol on the proliferation of neonatal keratinocytes, the expression of estrogen receptor isoforms, and the signaling mechanisms by which estradiol mediates cell growth. We demonstrate that estradiol binds neonatal keratinocytes with high affinity (Kd=5.2nM) and limited capacity (Bmax of 14.2fmol/mg...

Bone morphogenic protein-4 (BMP-4), a small secreted molecule belonging to the members of the transforming growth factor-beta family, when added to cultured human melanocytes (hMcytes), was shown to decrease the level of melanin and the expression of tyrosinase. To further delineate the mechanism by which BMP-4 regulates melanogenesis, we investiga...