Janusz Z Beer

Silver Spring Networks, 레드우드시티, California, United States

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Publications (77)189.98 Total impact

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    ABSTRACT: More than 375 genes have been identified that are involved in regulating skin pigmentation, and those act during development, survival, differentiation and/or responses of melanocytes to the environment. Many of those genes have been cloned and disruptions of their functions are associated with various pigmentary diseases, however many remain to be identified. We have performed a series of microarray analyses of hyperpigmented compared to less pigmented skin to identify genes responsible for those differences. The rationale and goal for this study was to perform a meta-analysis on those microarray databases to identify genes that may be significantly involved in regulating skin phenotype either directly or indirectly that might not have been identified due to subtle differences by any of those individual studies alone. The meta-analysis demonstrates that 1,271 probes representing 921 genes are differentially expressed at significant levels in the 5 microarray datasets compared, which provides new insights into the variety of genes involved in determining skin phenotype. Immunohistochemistry was used to validate 2 of those markers at the protein level (TRIM63 and QPCT) and we discuss the possible functions of those genes in regulating skin physiology.Journal of Investigative Dermatology accepted article preview online, 07 May 2015. doi:10.1038/jid.2015.179.
    No preview · Article · May 2015 · Journal of Investigative Dermatology
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    ABSTRACT: Human skin color, i.e. pigmentation, differs widely among individuals as do their responses to various types of ultraviolet radiation (UV) and their risks of skin cancer. In some individuals UV-induced pigmentation persists for months to years in a phenomenon termed long-lasting pigmentation (LLP). It is unclear whether LLP is an indicator of potential risk for skin cancer. LLP seems to have similar features to other forms of hyperpigmentation, e.g. solar lentigos or age spots, which are clinical markers of photodamage and risk factors for precancerous lesions. To investigate what UV-induced molecular changes may persist in individuals with LLP, clinical specimens from non-sunburn-inducing repeated UV exposures (UVA, UVB or UVA+UVB) at 4 months post-exposure (short-term LLP) were evaluated by microarray analysis and dataset mining. Validated targets were further evaluated in clinical specimens from 6 healthy individuals (3 LLP+ and 3 LLP-) followed for more than 9 months (long-term LLP) who initially received a single sunburn-inducing UVA+UVB exposure. The results support a UV-induced hyperpigmentation model in which basal keratinocytes have an impaired ability to remove melanin that leads to a compensatory mechanism by neighboring keratinocytes with increased proliferative capacity to maintain skin homeostasis. The attenuated expression of SOX7 and other hemidesmosomal components (integrin α6β4 and plectin) leads to increased melanosome uptake by keratinocytes and points to a spatial regulation within the epidermis. The reduced density of hemidesmosomes provides supporting evidence for plasticity at the epidermal-dermal junction. Altered hemidesmosome plasticity, and the sustained nature of LLP, may be mediated by the role of SOX7 in basal keratinocytes. The long-term sustained subtle changes detected are modest, but sufficient to create dramatic visual differences in skin color. These results suggest that the hyperpigmentation phenomenon leading to increased interdigitation develops in order to maintain normal skin homeostasis in individuals with LLP.
    No preview · Article · Dec 2014 · The Journal of Pathology
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    ABSTRACT: Differences in visible skin pigmentation give rise to the wide variation of skin colors seen in racial/ethnic populations. Skin pigmentation is important not only from cosmetic and psychological points of view, but more importantly because of its implications for the risk of all types of skin cancers, on photoaging, etc. Despite differences in those parameters in Caucasian and Asian skin types, they are remarkably similar in their production and distribution of melanins, and the mechanism(s) underlying their different characteristics have remained obscure. In this study, we used microarray analysis of skin suction blisters to investigate molecular differences underlying the determination of pigmentation in various skin types, and we used immunohistochemistry to validate the expression patterns of several interesting targets that were identified. Intriguingly, Caucasian and Asian skins had highly similar gene expression patterns that differed significantly from the pattern of African skin. The results of this study suggest the dynamic interactions of different types of cells in human skin that regulate its pigmentation, reveal that the known pigmentation genes have a limited contribution and uncover a new array of genes, including NINL and S100A4, that might be involved in that regulation.This article is protected by copyright. All rights reserved.
    No preview · Article · Jul 2014 · Experimental Dermatology
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    ABSTRACT: UV exposure causes a wide range of skin damage including cutaneous melanoma. The mechanisms of cellular and molecular damage, as well as those of erythemal and pigmentation responses to UV exposure, have largely been studied in the White population. This study systematically investigates responses to UV exposure in the Native Hawaiian and Pacific Islander (NHPI) and Asian populations living in Hawai'i (A/HI) as well as in Asians living in Maryland (A/MD). Our analyses indicate that the NHPI population is less sensitive to UV exposure than the A/HI population. Comparisons between the two Asian groups suggest that, despite slightly but not statistically different baseline constitutive pigmentation (pre-UV exposure), the A/HI and A/MD had similar UV sensitivity, measured as minimal erythemal dose (MED). However, the A/MD population had higher levels of oxyhemoglobin at doses of 2.0, 2.8 and 4.0 MED. Unexpectedly, the A/MD subjects retained higher levels of pigmentation 2 weeks post-UV exposure. This study provides insight into UV responses of the inhabitants of Hawai'i and shows that such responses are statistically significant for relatively small samples of NHPI and for A/HI and A/MD.
    No preview · Article · Jun 2013 · Photodermatology Photoimmunology and Photomedicine
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    ABSTRACT: The diversity of human skin phenotypes and the ubiquitous exposure to ultraviolet radiation (UVR) underscore the need for a non-invasive tool to predict an individual's UVR sensitivity. We analysed correlations between UVR sensitivity, melanin content, diffuse reflectance spectroscopy (DR) and UVR-induced DNA damage in the skin of subjects from three racial/ethnic groups: Asian, Black or African American and White. UVR sensitivity was determined by evaluating each subject's response to one minimal erythemal dose (MED) of UVR one day after the exposure. Melanin content was measured using DR and by densitometric analysis of Fontana-Masson staining (FM) in skin biopsies taken from unexposed areas. An individual's UVR sensitivity based on MED was highly correlated with melanin content measured by DR and by FM. Therefore, a predictive model for the non-invasive determination of UVR sensitivity using DR was developed. The MED precision was further improved when we took race/ethnicity into consideration. The use of DR serves as a tool for predicting UVR sensitivity in humans that should be invaluable for determining appropriate UVR doses for therapeutic, diagnostic and/or cosmetic devices.
    Full-text · Article · Apr 2013 · Experimental Dermatology
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    ABSTRACT: The Food and Drug Administration has published guidelines for manufacturer-recommended exposure schedules for ultraviolet (UV) tanning, intended to limit acute and delayed damage from UV exposure. These guidelines recommend that exposure schedules be adjusted for skin phototype. However, it has been shown that the dose necessary to produce tanning is similar for phototypes 2-4. We observed tanning in phototypes 2 and 3 from repeated UV exposures over a 5-week period. Pigmentation was evaluated visually, instrumentally, and through Fontana-Masson staining of biopsies. The resultant pigmentation was equal or greater in phototype 3 compared with phototype 2 - both visually and instrumentally - measured on day 31 of the exposure protocol. The amount of melanin measured in biopsies taken 24 h postexposure was also greater in phototype 3 compared with phototype 2. Published data on tanning in phototypes 4 and 5 support our findings that higher phototypes can develop pigmentation more efficiently than lower phototypes. Therefore, a universal exposure schedule (based on sensitivity of phototype 2) can be used for all phototypes that are expected to engage in indoor tanning. This approach will result in a reduction of the UV burden for skin phototypes 3 and above.
    No preview · Article · Aug 2012 · Photodermatology Photoimmunology and Photomedicine
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    Preview · Article · Aug 2011 · Pigment Cell & Melanoma Research
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    ABSTRACT: The incidence of skin cancer, including cutaneous melanoma, has risen substantially in recent years, and epidemiological and laboratory studies show that UV radiation is a major causative factor of this increase. UV damage also underlies photoaging of the skin, and these deleterious effects of UV can be, in part, prevented in skin with higher levels of constitutive pigmentation. We review the clinical studies we have made in recent years regarding the rapid and the long-term responses of the pigmentary system in human skin to UV exposure.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 32-35; doi:10.1038/jidsymp.2009.10.
    Full-text · Article · Sep 2009 · Journal of Investigative Dermatology Symposium Proceedings
  • Sharon A Miller · Janusz Z Beer · Varsha Savalia

    No preview · Article · Sep 2009 · Photodermatology Photoimmunology and Photomedicine
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    ABSTRACT: alpha-Hydroxy acids (alphaHAs) are reported to reduce signs of aging in the skin and are widely used cosmetic ingredients. Several studies suggest that alphaHA can increase the sensitivity of skin to ultraviolet radiation. More recently, beta-hydroxy acids (betaHAs), or combinations of alphaHA and betaHA have also been incorporated into antiaging skin care products. Concerns have also arisen about increased sensitivity to ultraviolet radiation following use of skin care products containing beta-HA. To determine whether topical treatment with glycolic acid, a representative alphaHA, or with salicylic acid, a betaHA, modifies the short-term effects of solar simulated radiation (SSR) in human skin. Fourteen subjects participated in this study. Three of the four test sites on the mid-back of each subject were treated daily Monday-Friday, for a total of 3.5 weeks, with glycolic acid (10%), salicylic acid (2%), or vehicle (control). The fourth site received no treatment. After the last treatment, each site was exposed to SSR, and shave biopsies from all four sites were obtained. The endpoints evaluated in this study were erythema (assessed visually and instrumentally), DNA damage and sunburn cell formation. Treatment with glycolic acid resulted in increased sensitivity of human skin to SSR, measured as an increase in erythema, DNA damage and sunburn cell formation. Salicylic acid did not produce significant changes in any of these biomarkers. Short-term topical application of glycolic acid in a cosmetic formulation increased the sensitivity of human skin to SSR, while a comparable treatment with salicylic acid did not.
    No preview · Article · Jun 2009 · Journal of dermatological science
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    Preview · Article · Mar 2009 · Pigment Cell & Melanoma Research
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    ABSTRACT: It is known that UV modulates the expression of paracrine factors that regulate melanocyte function in the skin. We investigated the consequences of repetitive UV exposure of human skin in biopsies of 10 subjects with phototypes 2-3.5 taken 1-4 years later. The expression of melanogenic factors (TYR, MART1, MITF), growth factors/receptors (SCF/KIT, bFGF/FGFR1, ET1/EDNRB, HGF, GM-CSF), adhesion molecules (beta-catenin, E-cadherin, N-cadherin), cell cycle proteins (PCNA, cyclins D1, E2) as well as Bcl-2, DKK1, and DKK3, were analyzed by immunohistochemistry. Most of those markers showed no detectable changes at > or = 1 year after the repetitive UV irradiation. Although increased expression of EDNRB protein was detected in 3 of 10 UV-irradiated subjects, there was no detectable change in the expression of ET1 protein or in EDNRB mRNA levels. In summary, only the expression of TYR, MART1, and/or EDNRB, and only in some subjects, was elevated at > or = 1 year after UV irradiation. Thus the long-term effects of repetitive UV irradiation on human skin did not lead to significant changes in skin morphology and there is considerable subject-to-subject variation in responses. The possibility that changes in the expression and function of EDNRB triggers downstream activation of abnormal melanocyte proliferation and differentiation deserves further investigation.
    Full-text · Article · Oct 2008 · Journal of Investigative Dermatology
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    ABSTRACT: The dynamics of ultraviolet (UV)-induced melanogenesis have been well characterized for single UV exposures. However, our knowledge of the effects of repeated UV exposures on the development of new pigmentation is limited. To characterize the dynamics and dose dependence of pigmentation induction by repeated UV exposures using two different UV sources. A total of 40 healthy subjects participated in the study: 21 were exposed to a 5% UVB/95% UVA source and 19 were exposed to a 2% UVB/98% UVA source. Skin phototypes 2-3 were represented. Subjects were exposed one to three times per week. The minimal erythemal dose and minimal melanogenic dose of all subjects were determined, and both visual and instrumental observations of the development of pigmentation and erythema were recorded. Dark-brown pigmentation could be produced by a cumulative UV dose of 4200 J m(-2) given as 10 exposures over 5 weeks. However, comparable pigmentation could also be induced by a cumulative dose of 2900 J m(-2) given as eight exposures over 4 weeks. The lowest cumulative dose of 1900 J m(-2) given over 4 weeks produced moderate pigmentation. The 2% UVB source led to earlier and darker pigmentation than the 5% UVB source did for equally erythemogenic doses. These observations show that the dynamics of melanogenesis induced by repeated exposures depends on UV dose, dose interval and emission spectrum. They also indicate that increasing the UV dose above a certain level of cumulative exposure does not significantly increase the level of UV-induced pigmentation.
    Full-text · Article · Aug 2008 · British Journal of Dermatology
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    G.N. Stamatas · B.Z. Zmudzka · N Kollias · J.Z. Beer
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    ABSTRACT: Various physical, chemical and biological insults, including exposure to ultraviolet (UV) radiation, cause erythema and change in pigmentation in human skin. These reactions provide an important measure of the cutaneous response to the insult. To present a new implementation of a method for objective in vivo measurement of erythema and pigmentation. The method is based on acquisition of reflectance spectra in the visible range using a commercially available spectrophotometer. The probe of this instrument incorporates an integrating sphere that captures the light remitted from the skin in a wide range of angles. We corrected the acquired reflectance spectra for the contribution of specular reflections by an amount given by the Fresnel equation and verified this correction experimentally. This correction is particularly important when measurements are performed on heavily pigmented skin. The corrected reflectance spectra are then transformed into absorbance spectra. To analyse these spectra, we developed an algorithm which can be used to calculate apparent concentrations of oxyhaemoglobin, deoxyhaemoglobin and melanin. This method was tested in clinical studies of skin reactions induced by exposure to UV radiation. These experiments involved three groups of subjects with progressively darker complexion (constitutive pigmentation). Each group consisted of 10 subjects. Erythema was measured 1 day after UV exposure, and pigmentation (melanin content) 1 week later. Results Distinct apparent absorbance spectra were obtained for dark, intermediate and fair skin. There was good agreement between reconstructed spectra and experimental data at relevant wavelengths. Difference absorption spectra were able to show the dose dependence of UV-induced responses, and erythema and pigmentation values obtained by the spectroscopic method showed good correlation with those derived by subjective visual grading. The results demonstrate that the presented methodology provides an objective noninvasive way of measuring UV-induced reactions independently of the level of constitutive pigmentation.
    Full-text · Article · Jun 2008 · British Journal of Dermatology
  • Yuji Yamaguchi · Janusz Z Beer · Vincent J Hearing
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    ABSTRACT: Ultraviolet (UV)-induced skin cancers, including melanomas and basal/squamous cell carcinomas, occur more frequently in individuals with fair skin than in those with dark skin. Melanin plays an important role in protecting the skin against UV radiation and levels of melanin correlate inversely with amounts of DNA damage induced by UV in human skin of different racial/ethnic groups. The objectives of this study are to review recent progress in our understanding of mechanisms underlying differences in cancer incidence in skins of different colors, particularly between Black and White skin. More specifically, we review DNA damage and apoptosis in various types of skin before and after exposure to UV in our human study protocols using a single UV dose, either one minimal erythema dose (MED) or a similar low dose of 180-200 J/m2. Our data and other published reports indicate that several major mechanisms underlie the increased rates of photocarcinogenesis in fair/light skin. First, UV-induced DNA damage in the lower epidermis (including keratinocyte stem cells and melanocytes) is more effectively prevented in darker skin. Second, rates of repair of DNA damage can differ significantly in individuals. Third, UV-induced apoptosis to remove potentially precancerous cells is significantly greater in darker skin. These results suggest that pigmented epidermis is an efficient UV filter and that UV damaged cells are removed more efficiently in darker skin. The combination of decreased DNA damage and more efficient removal of UV-damaged cells may play a critical role in the decreased photocarcinogenesis seen in individuals with darker skin.
    No preview · Article · May 2008 · Archives for Dermatological Research
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    ABSTRACT: Substantial differences in DNA damage caused by a single UV irradiation were found in our previous study on skin with different levels of constitutive pigmentation. In this study, we assessed whether facultative pigmentation induced by repeated UV irradiation is photoprotective. Three sites on the backs of 21 healthy subjects with type II-III skin were irradiated at 100-600 J/m(2) every 2-7 days over a 4- to 5-week period. The three sites received different cumulative doses of UV (1900, 2900 or 4200 J/m(2)) and were biopsied 1 day after the last irradiation. Biomarkers examined included pigment content assessed by Fontana-Masson staining, melanocyte function by expression of melanocyte-specific markers, DNA damage as cyclobutane pyrimidine dimers (CPD), nuclear accumulation of p53, apoptosis determined by TUNEL assay, and levels of p21 and Ser46-phosphorylated p53. Increases in melanocyte function and density, and in levels of apoptosis were similar among the 3 study sites irradiated with different cumulative UV doses. Levels of CPD decreased while the number of p53-positive cells increased as the cumulative dose of UV increased. These results suggest that pigmentation induced in skin by repeated UV irradiation protects against subsequent UV-induced DNA damage but not as effectively as constitutive pigmentation.
    Full-text · Article · Apr 2008 · Experimental Dermatology
  • S.A. Miller · S.G. Coelho · B.Z. Zmudzka · J.Z. Beer

    No preview · Article · Apr 2007
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    ABSTRACT: Pigmentation of human skin is closely involved in protection against environmental stresses, in particular exposure to ultraviolet (UV) radiation. It is well known that darker skin is significantly more resistant to the damaging effects of UV, such as photocarcinogenesis and photoaging, than is lighter skin. Constitutive skin pigmentation depends on the amount of melanin and its distribution in that tissue. Melanin is significantly photoprotective and epidermal cells in darker skin incur less DNA damage than do those in lighter skin. This review summarizes current understanding of the regulation of constitutive human skin pigmentation and responses to UV radiation, with emphasis on physiological factors that influence those processes. Further research is needed to characterize the role of skin pigmentation to reduce photocarcinogenesis and to develop effective strategies to minimize such risks.
    Full-text · Article · Mar 2007 · Pigment Cell Research

  • No preview · Article · Jan 2007 · Photodermatology Photoimmunology and Photomedicine
  • Barbara Z Zmudzka · Vincent J Hearing · Janusz Z Beer

    No preview · Article · Oct 2006 · Journal of Photochemistry and Photobiology B Biology

Publication Stats

1k Citations
189.98 Total Impact Points


  • 2009-2015
    • Silver Spring Networks
      레드우드시티, California, United States
  • 1993-2011
    • U.S. Food and Drug Administration
      • • Center for Devices and Radiological Health
      • • Division of Biochemical Toxicology
      Washington, Washington, D.C., United States
  • 2005
    • National Institutes of Health
      • Laboratory of Cell Biology
      Bethesda, MD, United States
  • 2004
    • New York State
      New York, New York, United States
  • 1997
    • University of Texas Southwestern Medical Center
      • Department of Dermatology
      Dallas, Texas, United States
  • 1994
    • Johns Hopkins Medicine
      • Department of Dermatology
      Baltimore, Maryland, United States