Publications by authors named "Helen He"

33 Publications

Mild atopic dermatitis lacks systemic inflammation and shows reduced nonlesional skin abnormalities.

J Allergy Clin Immunol 2020 Oct 1. Epub 2020 Oct 1.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Background: Molecular studies in atopic dermatitis (AD) are largely restricted to patients with moderate-to-severe disease.

Objective: Our aim was to evaluate skin and blood abnormalities in mild, moderate, and severe AD.

Methods: Skin and blood samples were obtained from 61 patients with AD (20 with mild or limited disease, 17 with moderate disease, and 24 with severe disease) and 20 healthy subjects. Immune and barrier markers were measured in lesional, nonlesional, and healthy skin by quantitative real-time PCR and immunohistochemistry, and in blood by using the OLINK proteomic assay.

Results: Cellular markers of epidermal hyperplasia and T-cell/dendritic cell infiltration were increased in AD tissues of all patients in all severity groups versus in those of controls, whereas downstream T2 cell-, T22 cell-, T1 cell-, and T17 cell-related mediators demonstrated incremental elevations with increasing disease severity, in both lesional and nonlesional skin. Whereas the levels of the T2 (IL13, CCL17, and CCL26) and T22 (IL-22) cytokines were significantly elevated in both AD lesional and nonlesional skin of all patients regardless of the severity of their disease, patients with mild or limited AD showed increases in their levels of T1 cell (IFNG, CXCL9, and CXCL10) and T17 cell (IL-17A, CCL20, and CXCL1) markers in lesional but not nonlesional skin. Regulatory T-cell-related mediators (IL-10 and FOXP3) were comparably upregulated in all groups, without displaying the severity-based gradient in other immune axes. Unsupervised clustering aligned samples along a severity spectrum, where nonlesional mild or limited AD skin clustered with the samples from healthy controls. Furthermore, whereas the blood profiles of patients with moderate and severe AD showed gradual increases in the levels of T1 cell-, T2 cell-, and T17 cell-related and atherosclerosis and/or cardiovascular risk (CCL7, FGF21, and IGFBP1) proteins, the blood profiles of patients with mild or limited AD lacked significant differences from those of the controls.

Conclusion: Mild and limited AD show high levels of T2/T22 cell activation that is primarily localized to skin lesions and lacks the systemic inflammation of moderate and severe disease.
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http://dx.doi.org/10.1016/j.jaci.2020.08.041DOI Listing
October 2020

Tape-Strip Proteomic Profiling of Atopic Dermatitis on Dupilumab Identifies Minimally Invasive Biomarkers.

Front Immunol 2020 6;11:1768. Epub 2020 Aug 6.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Tape-stripping is a minimally invasive approach for skin sampling that captures the cutaneous immune/barrier abnormalities in atopic dermatitis (AD). However, tape-strips have not been used to evaluate molecular changes with therapeutic targeting. In this study, we sought to characterize the proteomic signature of tape-strips from AD patients, before and after dupilumab therapy. Twenty-six AD patients were treated with every-other-week dupilumab 300 mg for 16 weeks. Tape-strips from lesional and non-lesional skin were collected before and after treatment, and analyzed with the Olink proteomic assay. Using criteria of fold-change>1.5 and FDR < 0.05, 136 proteins significantly decreased after dupilumab treatment, corresponding to an overall mean improvement of 66.2% in the lesional vs. non-lesional AD proteome. Significant decreases after dupilumab were observed in immune markers related to general inflammation (MMP12), Th2 (CCL13/CCL17), Th17/Th22 (IL-12B, CXCL1, S100A12), and innate immunity (IL-6, IL-8, IL-17C), while the Th1 chemokines CXCL9/CXCL10 remained elevated. Proteins related to atherosclerosis/cardiovascular risk (e.g., SELE/E-selectin, IGFBP7, CHIT1/ chitotriosidase-1, AXL) also significantly decreased after treatment. Dupilumab therapy suppressed AD-related immune biomarkers and atherosclerosis/cardiovascular risk proteins. Tape-strip proteomics may be useful for monitoring therapeutic response in real-life settings, clinical trials, and longitudinal studies for AD and beyond.
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http://dx.doi.org/10.3389/fimmu.2020.01768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7423990PMC
August 2020

Tape strips detect distinct immune and barrier profiles in atopic dermatitis and psoriasis.

J Allergy Clin Immunol 2021 Jan 21;147(1):199-212. Epub 2020 Jul 21.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory of Investigative Dermatology, The Rockefeller University, New York, NY. Electronic address:

Background: Our current understanding of atopic dermatitis (AD) and psoriasis pathophysiology is largely derived from skin biopsy studies that cause scarring and may be impractical in large-scale clinical trials. Although tape strips show promise as a minimally invasive technique in these common diseases, a comprehensive molecular profiling characterizing and differentiating the 2 diseases in tape strips is unavailable.

Objective: Our aim was to construct a global transcriptome of tape strips from lesional and nonlesional skin of adults with moderate-to-severe AD and psoriasis.

Methods: A total of 20 tape strips were obtained from lesional and nonlesional skin of patients with AD and psoriasis and skin from controls (n = 20 each); the strips were subjected to RNA sequencing (RNA-seq), with quantitative RT-PCR validation of immune and barrier biomarkers.

Results: We detected RNA-seq profiles in 96 of 100 of samples (96%), with 4123 and 5390 genes differentially expressed in AD and psoriasis lesions versus in controls, respectively (fold change ≥ 2; false discovery rate [FDR] < 0.05). Nonlesional tape-stripped skin from patients with AD was more similar to lesional skin than to nonlesional skin of patients with psoriasis, which showed larger differentiation from lesions. AD and psoriasis tissues shared increases in levels of dendritic cell and T-cell markers (CD3, ITGAX/CD11c, and CD83), but AD tissues showed preferential T2 skewing (IL-13, CCL17/TARC, and CCL18), whereas psoriasis was characterized by higher levels of expression of T17-related (IL-17A/F and IL-36A/IL-36G), T1-related (IFN-γ and CXCL9/CXCL10), and innate immunity-related (nitric oxide synthase 2/inducible nitric oxide synthase and IL-17C) products (FDR < 0.05). Terminal differentiation (FLG2 and LCE5A), tight junction (CLDN8), and lipid biosynthesis and metabolism (FA2H and ALOXE3) products were significantly downregulated in both AD and psoriasis (FDR < 0.05). Nitric oxide synthase 2/inducible nitric oxide synthase expression (determined by quantitative PCR) differentiated AD and psoriasis with 100% accuracy.

Conclusion: RNA-seq tape strip profiling detected distinct immune and barrier signatures in lesional and nonlesional AD and psoriasis skin, suggesting their utility as a minimally invasive alternative to biopsies for detecting disease biomarkers.
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http://dx.doi.org/10.1016/j.jaci.2020.05.048DOI Listing
January 2021

Immunogenicity and Safety of a Tetravalent Recombinant Subunit Dengue Vaccine in Adults Previously Vaccinated with a Live Attenuated Tetravalent Dengue Vaccine: Results of a Phase-I Randomized Clinical Trial.

Am J Trop Med Hyg 2020 08 7;103(2):855-863. Epub 2020 May 7.

Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland.

New dengue vaccines are needed to prevent this globally expanding vector-borne disease. The V180 vaccine candidate consists of four recombinant, soluble, dengue virus envelope glycoproteins and has been previously evaluated in two clinical trials for safety and immunogenicity in -naive participants (NCT01477580 and NCT0093642). Here, we report on a randomized, placebo-controlled, double-blind study of the safety and immunogenicity of the V180 vaccine in subjects who have previously received the live attenuated tetravalent vaccine (LATV) developed by the National Institute of Allergy and Infectious Diseases (protocol #V180-002 [CIR-301]). The study was designed to evaluate whether this recombinant subunit vaccine could boost the neutralizing antibody responses induced by dengue LATV. Twenty participants who had previously received one or two doses of dengue LATV were randomized and received a single dose of V180 nonadjuvanted ( = 8), V180 adjuvanted with Alhydrogel™ (aluminum hydroxide gel, Brenntag Biosector, Frederikssund, Denmark) ( = 8), or placebo ( = 4). Immunogenicity was measured using a plaque reduction neutralization test at days 1, 15, 28, and 180 after vaccination. In addition, vaccine safety (solicited and unsolicited adverse events) was assessed using a vaccination report card for 28 days following vaccination, and serious adverse events were captured from the time of informed consent through the final study visit at 6 months after vaccination. The results of the study demonstrate that the V180 vaccine is generally well tolerated and immunogenic in these dengue-seropositive volunteers.
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http://dx.doi.org/10.4269/ajtmh.20-0042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410446PMC
August 2020

Single-cell transcriptome analysis of human skin identifies novel fibroblast subpopulation and enrichment of immune subsets in atopic dermatitis.

J Allergy Clin Immunol 2020 06 7;145(6):1615-1628. Epub 2020 Feb 7.

Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Background: Atopic dermatitis (AD) is a prevalent inflammatory skin disease with a complex pathogenesis involving immune cell and epidermal abnormalities. Despite whole tissue biopsy studies that have advanced the mechanistic understanding of AD, single cell-based molecular alterations are largely unknown.

Objective: Our aims were to construct a detailed, high-resolution atlas of cell populations and assess variability in cell composition and cell-specific gene expression in the skin of patients with AD versus in controls.

Methods: We performed single-cell RNA sequencing on skin biopsy specimens from 5 patients with AD (4 lesional samples and 5 nonlesional samples) and 7 healthy control subjects, using 10× Genomics.

Results: We created transcriptomic profiles for 39,042 AD (lesional and nonlesional) and healthy skin cells. Fibroblasts demonstrated a novel COL6A5COL18A1 subpopulation that was unique to lesional AD and expressed CCL2 and CCL19 cytokines. A corresponding LAMP3 dendritic cell (DC) population that expressed the CCL19 receptor CCR7 was also unique to AD lesions, illustrating a potential role for fibroblast signaling to immune cells. The lesional AD samples were characterized by expansion of inflammatory DCs (CD1AFCER1A) and tissue-resident memory T cells (CD69CD103). The frequencies of type 2 (IL13)/type 22 (IL22) T cells were higher than those of type 1 (IFNG) in lesional AD, whereas this ratio was slightly diminished in nonlesional AD and further diminished in controls.

Conclusion: AD lesions were characterized by expanded type 2/type 22 T cells and inflammatory DCs, and by a unique inflammatory fibroblast that may interact with immune cells to regulate lymphoid cell organization and type 2 inflammation.
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http://dx.doi.org/10.1016/j.jaci.2020.01.042DOI Listing
June 2020

Granuloma annulare skin profile shows activation of T-helper cell type 1, T-helper cell type 2, and Janus kinase pathways.

J Am Acad Dermatol 2020 Jul 20;83(1):63-70. Epub 2019 Dec 20.

Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York; Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York. Electronic address:

Background: Granuloma annulare (GA) is an inflammatory skin disorder. Localized GA is often self-resolving, but generalized GA is often recalcitrant to treatments. There are no targeted treatments for GA, largely due to lack of mechanistic understanding. Recently, tumor necrosis factor antagonism showed promise in GA, suggesting an underlying immune pathogenesis.

Objective: To elucidate the immune pathogenesis and identify potential therapeutic targets for GA.

Methods: Lesional and nonlesional skin biopsy samples were obtained from patients with GA and evaluated for a large array of inflammatory markers compared with inflammatory markers from normal skin of healthy individuals.

Results: We found differential expression of many inflammatory genes compared with normal skin. These genes were associated with T-helper (Th) cell type 1/innate immunity (tumor necrosis factor-α, interleukin [IL]-1β, IL-12/23p40, signal transducer and activator of transcription 1, chemokine [C-X-C motif] ligand 9/10), Janus kinase signaling, and Th2 (IL-4, IL-31, chemokine (C-C motif) ligands 17 and 18; P < .05). Unexpectedly, IL-4 showed significant upregulation in GA lesional skin vs control skin (15,600-fold change).

Limitations: Limited sample size.

Conclusions: Our findings shed light on the inflammatory pathways of GA, supporting the notion that immune mechanisms could be driving disease, as suggested by the promising data of tumor necrosis factor-α inhibitors in GA. The significant Janus kinase and particularly Th2 signaling in GA advocates for the investigation of specific Janus kinase- and Th2- targeted drug therapy.
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http://dx.doi.org/10.1016/j.jaad.2019.12.028DOI Listing
July 2020

The proteomic skin profile of moderate-to-severe atopic dermatitis patients shows an inflammatory signature.

J Am Acad Dermatol 2020 Mar 25;82(3):690-699. Epub 2019 Oct 25.

Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

Background: Moderate-to-severe atopic dermatitis (AD) is increasingly recognized as a systemic disease, largely due to proteomic blood studies. There are growing efforts to develop AD biomarkers using minimal tissues.

Objective: To characterize the AD skin proteomic signature and its relationship with the blood proteome and genomic skin profile in the same individuals.

Methods: We evaluated lesional and nonlesional biopsy samples and blood from 20 individuals with moderate-to-severe AD and 28 healthy individuals using Olink Proteomics (Uppsala, Sweden), using 10 μg/10 μL for skin and blood and RNA sequencing of the skin.

Results: The AD skin proteome demonstrated significant upregulation in lesional and even in nonlesional skin compared with controls in inflammatory markers (matrix metalloproteinase 12; T-helper cell [Th]2/interleukin [IL]-1 receptor-like 1[IL1RL1]/IL-33R, IL-13, chemokine [C-C motif] ligand [CCL] 17; Th1/C-X-C motif chemokine 10; Th17/Th22/PI3, CCL20, S100A12), and in cardiovascular-associated proteins (E-selectin, matrix metalloproteinases, platelet growth factor, myeloperoxidase, fatty acid binding protein 4, and vascular endothelial growth factor A; false discovery rate, <0.05). Skin proteins demonstrated much higher and significant upregulations (vs controls) compared with blood, suggesting a skin source for the inflammatory/cardiovascular profile. Gene and protein expressions were correlated (r = 0.410, P < .001), with commonly upregulated inflammatory and cardiovascular risk-associated products, suggesting protein translation in skin.

Limitations: Our analysis was limited to 354 proteins.

Conclusions: The AD skin proteome shows an inflammatory and cardiovascular signature even in nonlesional skin, emphasizing the need for proactive treatment. Skin proteomics presents a sensitive option for biomarker monitoring.
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http://dx.doi.org/10.1016/j.jaad.2019.10.039DOI Listing
March 2020

Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood.

J Allergy Clin Immunol 2020 01 15;145(1):215-228. Epub 2019 Oct 15.

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Background: The circulating immune phenotype was defined in adults and young children with early atopic dermatitis (AD), but chronologic changes in the blood of infants and children with AD through adolescence have not been explored.

Objective: We sought to compare immune activation and cytokine polarization in the blood of 0- to 5-year-old (n = 39), 6- to 11-year-old (n = 26), 12- to 17-year-old (n = 21) and 18-year-old or older (n = 43) patients with AD versus age-matched control subjects.

Methods: Flow cytometry was used to measure IFN-γ, IL-9, IL-13, IL-17, and IL-22 cytokine levels in CD4/CD8 T cells, with inducible costimulator molecule and HLA-DR defining midterm and long-term T-cell activation, respectively, within skin-homing/cutaneous lymphocyte antigen (CLA) versus systemic/CLA T cells. Unsupervised clustering differentiated patients based on their blood biomarker frequencies.

Results: Although CLA T1 frequencies were significantly lower in infants with AD versus all older patients (P < .01), frequencies of CLA T2 T cells were similarly expanded across all AD age groups compared with control subjects (P < .05). After infancy, CLA T2 frequencies were increased in patients with AD in all age groups, suggesting systemic immune activation with disease chronicity. IL-22 frequencies serially increased from normal levels in infants to highly significant levels in adolescents and adults compared with levels in respective control subjects (P < .01). Unsupervised clustering aligned the AD profiles along an age-related spectrum from infancy to adulthood (eg, inducible costimulator molecule and IL-22).

Conclusions: The adult AD phenotype is achieved only in adulthood. Unique cytokine signatures characterizing individual pediatric endotypes might require age-specific therapies. Future longitudinal studies, comparing the profile of patients with cleared versus persistent pediatric AD, might define age-specific changes that predict AD clearance.
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http://dx.doi.org/10.1016/j.jaci.2019.09.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957229PMC
January 2020

Increased cardiovascular and atherosclerosis markers in blood of older patients with atopic dermatitis.

Ann Allergy Asthma Immunol 2020 01 14;124(1):70-78. Epub 2019 Oct 14.

Department of Dermatology, Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address:

Background: Atopic dermatitis (AD) is associated with increased systemic inflammation and cardiovascular risk. Although previous studies have found increased inflammatory proteins in the blood of patients with AD, detailed comparison among patients with AD of different ages is unavailable.

Objective: To characterize the blood proteomic signature of patients with AD as a function of age.

Methods: We used the OLINK high-throughput proteomic assay to measure serum inflammatory and cardiovascular risk proteins in 71 patients with moderate to severe AD from 3 age groups (18-40 years old [n = 26], 41-60 years old [n = 24], and >60 years old [n = 21]) compared with 37 age-matched controls. Total and allergen-specific serum IgEs were also measured.

Results: When we compared patients with AD from 3 different age groups with their respective controls, we identified a total of 172 differentially expressed proteins. T2 chemokines (CCL13, CCL17) were consistently elevated in patients with AD across all ages (P < .05), whereas T1 (CXCL10) and T17 (KYNU, CCL20) markers incrementally increased with age in both patients with AD and healthy subjects. Elderly patients with AD (>60 years old) exhibited striking upregulation of key proinflammatory proteins, including markers of atherosclerosis (CCL4, CCL7, SORT1), cardiovascular risk (GDF15, MPO, ST2), cell adhesion (CDH3), and apoptosis (FAS; all P < .05) compared with younger patients with AD and age-matched controls. We also found that total and allergen-specific serum IgEs decreased significantly with age in patients with AD (P < .05).

Conclusion: Elderly patients with AD had increased levels of systemic inflammatory markers, including those associated with cardiovascular and atherosclerosis risk, which may explain their increased incidence of cardiovascular disease. This finding suggests that older patients with AD may benefit from cardiovascular disease screening and prevention.
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http://dx.doi.org/10.1016/j.anai.2019.10.013DOI Listing
January 2020

Needs assessment for improving library support for dentistry researchers.

J Med Libr Assoc 2019 Jul 1;107(3):352-363. Epub 2019 Jul 1.

Intern, Toronto Academic Libraries (TALint Program), Dentistry Library, University of Toronto, Toronto, ON, Canada,

Objective: To better support dentistry researchers in the ever-changing landscape of scholarly research, academic librarians need to redefine their roles and discover new ways to be involved at each stage of the research cycle. A needs assessment survey was conducted to evaluate faculty members' research support needs and allow a more targeted approach to the development of research services in an academic health sciences library.

Methods: The anonymous, web-based survey was distributed via email to full-time researchers at the Faculty of Dentistry, University of Toronto. The survey included twenty questions inquiring about researchers' needs and behaviors across three stages of the research cycle: funding and grant applications, publication and dissemination, and research impact assessment. Data were also collected on researchers' use of grey literature to identify whether current library efforts to support researchers should be improved in this area.

Results: Among library services, researchers considered support for funding and grant applications most valuable and grey literature support least valuable. Researcher engagement with open access publishing models was low, and few participants had self-archived their publications in the university's institutional repository. Participants reported low interest in altmetrics, and few used online tools to promote or share their research results.

Conclusions: Findings indicate that increased efforts should be made to promote and develop services for funding and grant applications. New services are needed to assist researchers in maximizing their research impact and to increase researcher awareness of the benefits of open access publishing models, self-archiving, and altmetrics.
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http://dx.doi.org/10.5195/jmla.2019.556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6579589PMC
July 2019

The blood proteomic signature of early-onset pediatric atopic dermatitis shows systemic inflammation and is distinct from adult long-standing disease.

J Am Acad Dermatol 2019 Aug 19;81(2):510-519. Epub 2019 Apr 19.

Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois. Electronic address:

Background: Despite increasing evidence that adults with long-standing atopic dermatitis (AD) have systemic inflammation, little is known about systemic inflammation in recent-onset early pediatric AD.

Objective: To analyze blood inflammatory proteins of early pediatric AD.

Methods: Using high-throughput proteomics (proximity extension assay), we assessed 257 inflammatory and cardiovascular risk proteins in the blood of 30 children with moderate to severe AD younger than 5 years of age (within 6 months of onset) compared with age-matched pediatric control individuals and adult patients with AD.

Results: In pediatric AD blood, T helper (Th) type 2 (CCL13, CCL22) and Th17 (peptidase inhibitor-3/elafin) markers were increased, together with markers of tissue remodeling (matrix metalloproteinases 3/9/10, urokinase receptor), endothelial activation (E-selectin), T-cell activation (IL2RA), neutrophil activation (myeloperoxidase), lipid metabolism (FABP4), and growth factors (FGF21, transforming growth factor-α). Total numbers of dysregulated proteins were smaller in pediatric AD (n = 22) than in adult AD (n = 61). Clinical severity scores were positively correlated with receptors for interleukins 33 and 36 and inversely correlated with some Th1 markers (interferon gamma, CXCL11).

Limitations: Different baseline expression levels in healthy pediatric vs adult samples.

Conclusions: Within months of pediatric AD onset, systemic immune activation is present, with Th2/Th17 skewing but otherwise different proteomic patterns from adult AD. Future correlation of proteomic patterns with disease course, comorbidity development, and drug response may yield predictive biomarkers.
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http://dx.doi.org/10.1016/j.jaad.2019.04.036DOI Listing
August 2019

Correction to: JAK Inhibitors for Atopic Dermatitis: An Update.

Am J Clin Dermatol 2019 04;20(2):193

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, 5 E. 98th Street, New York, NY, 10029, USA.

Page 7, Table 1, ASN002 row. The cell entry in column 4, "Manufacturer", which previously read.
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http://dx.doi.org/10.1007/s40257-019-00421-1DOI Listing
April 2019

Atopic dermatitis endotypes and implications for targeted therapeutics.

J Allergy Clin Immunol 2019 01;143(1):1-11

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY. Electronic address:

Recent research advancements indicate that atopic dermatitis (AD) is a complex disease characterized by different subtypes/phenotypes based on age, disease chronicity, ethnicity, filaggrin and IgE status, and underlying molecular mechanisms/endotypes. This heterogeneity advocates against the traditional "one-size-fits-all" therapeutic approaches still used to manage AD. Precision medicine approaches, striving for targeted, tailored, endotype-driven disease prevention and treatment, rely on detailed definitions of the disease's variability across different phenotypes. Studies have shown that AD harbors different endotypes across different age groups and ethnicities and according to IgE levels and filaggrin mutation status. These include European American versus Asian patients, children versus adults, intrinsic versus extrinsic (IgE status) disease, and patients with and without filaggrin mutations. Therapies targeting different cytokine axes and other mechanisms involved in disease pathogenesis, which are currently being tested for patients with AD across the disease spectrum, will expand our ability to dissect the relative contribution of each of these pathways to disease perpetuation.
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http://dx.doi.org/10.1016/j.jaci.2018.10.032DOI Listing
January 2019

Blood endotyping distinguishes the profile of vitiligo from that of other inflammatory and autoimmune skin diseases.

J Allergy Clin Immunol 2019 06 18;143(6):2095-2107. Epub 2018 Dec 18.

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Background: Peripheral blood skin-homing/cutaneous lymphocyte antigen (CLA) T cells emerge as biomarkers of cutaneous immune activation in patients with inflammatory skin diseases (atopic dermatitis [AD] and alopecia areata [AA]). However, blood phenotyping across these subsets is not yet available in patients with vitiligo.

Objective: We sought to measure cytokine production by circulating skin-homing (CLA) versus systemic (CLA) "polar" CD4/CD8 ratio and activated T-cell subsets in patients with vitiligo compared with patients with AA, AD, or psoriasis and control subjects.

Methods: Flow cytometry was used to measure levels of the cytokines IFN-γ, IL-13, IL-9, IL-17, and IL-22 in CD4/CD8 T cells in the blood of 19 patients with moderate-to-severe nonsegmental/generalized vitiligo, moderate-to-severe AA (n = 32), psoriasis (n = 24), or AD (n = 43) and control subjects (n = 30). Unsupervised clustering differentiated subjects into groups based on cellular frequencies.

Results: Patients with Vitiligo showed the highest CLA/CLA T1/type 1 cytotoxic T-cell polarization, with parallel T2/T9/T17/T22 level increases to levels often greater than those seen in patients with AA, AD, or psoriasis (P < .05). Total regulatory T-cell counts were lower in patients with vitiligo than in control subjects and patients with AD or psoriasis (P < .001). Vitiligo severity correlated with levels of multiple cytokines (P < .1), whereas duration was linked with IFN-γ and IL-17 levels (P < .04). Patients and control subjects grouped into separate clusters based on blood biomarkers.

Conclusions: Vitiligo is characterized by a multicytokine polarization among circulating skin-homing and systemic subsets, which differentiates it from other inflammatory/autoimmune skin diseases. Future targeted therapies should delineate the relative contribution of each cytokine axis to disease perpetuation.
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http://dx.doi.org/10.1016/j.jaci.2018.11.031DOI Listing
June 2019

JAK Inhibitors for Atopic Dermatitis: An Update.

Am J Clin Dermatol 2019 Apr;20(2):181-192

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, 5 E. 98th Street, New York, NY, 10029, USA.

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases. AD is driven by barrier dysfunction and abnormal immune activation of T helper (Th) 2, Th22, and varying degrees of Th1 and Th17 among various subtypes. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and spleen tyrosine kinase (SYK) pathways are involved in signaling of several AD-related cytokines, such as IFN-γ, IL-4, IL-13, IL-31, IL-33, IL-23, IL-22, and IL-17, mediating downstream inflammation and barrier alterations. While AD is primarily Th2-driven, the clinical and molecular heterogeneity of AD endotypes highlights the unmet need for effective therapeutic options that target more than one immune axis and are safe for long-term use. The JAK inhibitors, which target different combinations of kinases, have overlapping but distinct mechanisms of action and safety profiles. Several topical and oral JAK inhibitors have been shown to decrease AD severity and symptoms. A review of the JAK and SYK inhibitors that are currently undergoing evaluation for efficacy and safety in the treatment of AD summarizes available data on a promising area of therapeutics and further elucidates the complex molecular interactions that drive AD.
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http://dx.doi.org/10.1007/s40257-018-0413-2DOI Listing
April 2019

Development of a Point-Of-Care Cardiovascular Ultrasound Program for Preclinical Medical Students.

J Am Soc Echocardiogr 2018 09 7;31(9):1064-1066.e2. Epub 2018 Jul 7.

Icahn School of Medicine at Mount Sinai, New York, New York; Cardiovascular Institute, Mount Sinai Hospital, New York, New York; Division of Cardiology, Department of Medicine, New York Presbyterian Hospital/Weill Cornell Medicine, New York, New York.

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http://dx.doi.org/10.1016/j.echo.2018.05.008DOI Listing
September 2018

Author Correction: The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins.

Sci Rep 2018 May 29;8(1):8439. Epub 2018 May 29.

The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-26378-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974294PMC
May 2018

Ichthyosis molecular fingerprinting shows profound T17 skewing and a unique barrier genomic signature.

J Allergy Clin Immunol 2019 02 24;143(2):604-618. Epub 2018 May 24.

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY. Electronic address:

Background: Ichthyoses are a group of rare skin disorders lacking effective treatments. Although genetic mutations are progressively delineated, comprehensive molecular phenotyping of ichthyotic skin could suggest much-needed pathogenesis-based therapy.

Objective: We sought to profile the molecular fingerprint of the most common orphan ichthyoses.

Methods: Gene, protein, and serum studies were performed on skin and blood samples from 29 patients (congenital ichthyosiform erythroderma, n = 9; lamellar ichthyosis, n = 8; epidermolytic ichthyosis, n = 8; and Netherton syndrome, n = 4), as well as age-matched healthy control subjects (n = 14), patients with psoriasis (n = 30), and patients with atopic dermatitis (AD; n = 16).

Results: Using criteria of a fold change of greater than 2 and a false discovery rate of less than 0.05, 132 differentially expressed genes were shared commonly among all ichthyoses, including many IL-17 and TNF-α-coregulated genes, which are considered hallmarks of psoriasis (defensin beta 4A, kynureninase, and vanin 3). Although striking upregulation of TH17 pathway genes (IL17F and IL36B/G) resembling that seen in patients with psoriasis was common to all patients with ichthyoses in a severity-related manner, patients with Netherton syndrome showed the greatest T-cell activation (inducible costimulator [ICOS]) and a broader immune phenotype with T1/IFN-γ, OASL, and T2/IL-4 receptor/IL-5 skewing, although less than seen in patients with AD (all P < .05). Ichthyoses lacked the epidermal differentiation and tight junction alterations of patients with AD (loricrin, filaggrin, and claudin 1) but showed characteristic alterations in lipid metabolism genes (ELOVL fatty acid elongase 3 and galanin), with parallel reductions in extracellular lipids and corneocyte compaction in all ichthyoses except epidermolytic ichthyosis, suggesting phenotypic variations. Transepidermal water loss, a functional barrier measure, significantly correlated with IL-17-regulated gene expression (IL17F and IL36A/IL36B/IL36G).

Conclusion: Similar to patients with AD and psoriasis, in whom cytokine dysregulation and barrier impairment orchestrate disease phenotypes, psoriasis-like immune dysregulation and lipid alterations characterize the ichthyoses. These data support the testing of IL-17/IL-36-targeted therapeutics for patients with ichthyosis similar to those used in patients with psoriasis.
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http://dx.doi.org/10.1016/j.jaci.2018.03.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195861PMC
February 2019

The Major Orphan Forms of Ichthyosis Are Characterized by Systemic T-Cell Activation and Th-17/Tc-17/Th-22/Tc-22 Polarization in Blood.

J Invest Dermatol 2018 10 14;138(10):2157-2167. Epub 2018 Apr 14.

Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Illinois, USA. Electronic address:

The ichthyoses are rare skin disorders with immune and barrier aberrations. Identifying blood phenotypes may advance targeted therapeutics. We aimed to compare frequencies of skin homing/cutaneous lymphocyte antigen (+) versus systemic/cutaneous lymphocyte antigen (-) "polar" CD4/CD8 and activated T-cell subsets in ichthyosis versus atopic dermatitis, psoriasis, and control blood, with appropriate clinical correlations. Flow cytometry was used to measure IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines in CD4/CD8 T cells, with inducible co-stimulator molecule and HLA-DR defining mid- and long-term T-cell activation, respectively. We compared peripheral blood from 47 patients with ichthyosis (congenital ichthyosiform erythroderma, lamellar ichthyosis, epidermolytic ichthyosis, and Netherton syndrome) with 43 patients with atopic dermatitis and 24 patients with psoriasis and 59 age-matched controls. Clinical measures included the ichthyosis severity score, with subsets for erythema and scaling, transepidermal water loss, and pruritus. All ichthyoses had excessive inducible co-stimulator molecule activation (P < 0.001), particularly epidermolytic ichthyosis. Significantly elevated IL-17- (P < 0.05) and IL-22-producing (P < 0.01) T cells characterized ichthyoses, mainly Netherton syndrome and congenital ichthyosiform erythroderma (P < 0.05). Increased T helper 2/cytotoxic T cell 2/T helper 9 (P < 0.05) and similar IFN-γ frequencies (P > 0.1) versus controls were also noted. IL-17/IL-22-producing cells clustered with clinical measures, whereas IFN-γ clustered with age. Our data show peripheral blood IL-17/IL-22 activation across the ichthyoses, correlating with clinical measures. Targeted therapies should dissect the relative contribution of polar cytokines to disease pathogenesis.
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http://dx.doi.org/10.1016/j.jid.2018.03.1523DOI Listing
October 2018

The atopic dermatitis blood signature is characterized by increases in inflammatory and cardiovascular risk proteins.

Sci Rep 2017 08 18;7(1):8707. Epub 2017 Aug 18.

The Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY, USA.

Beyond classic "allergic"/atopic comorbidities, atopic dermatitis (AD) emerges as systemic disease with increased cardiovascular risk. To better define serum inflammatory and cardiovascular risk proteins, we used an OLINK high-throughput proteomic assay to analyze moderate-to-severe AD (n = 59) compared to psoriasis (n = 22) and healthy controls (n = 18). Compared to controls, 10 proteins were increased in serum of both diseases, including Th1 (IFN-γ, CXCL9, TNF-β) and Th17 (CCL20) markers. 48 proteins each were uniquely upregulated in AD and psoriasis. Consistent with skin expression, AD serum showed up-regulation of Th2 (IL-13, CCL17, eotaxin-1/CCL11, CCL13, CCL4, IL-10), Th1 (CXCL10, CXCL11) and Th1/Th17/Th22 (IL-12/IL-23p40) responses. Surprisingly, some markers of atherosclerosis (fractalkine/CX3CL1, CCL8, M-CSF, HGF), T-cell development/activation (CD40L, IL-7, CCL25, IL-2RB, IL-15RA, CD6) and angiogenesis (VEGF-A) were significantly increased only in AD. Multiple inflammatory pathways showed stronger enrichment in AD than psoriasis. Several atherosclerosis mediators in serum (e.g. E-selectin, PI3/elafin, CCL7, IL-16) correlated with SCORAD, but not BMI. Also, AD inflammatory mediators (e.g. MMP12, IL-12/IL-23p40, CXCL9, CCL22, PI3/Elafin) correlated between blood and lesional as well as non-lesional skin. Overall, the AD blood signature was largely different compared to psoriasis, with dysregulation of inflammatory and cardiovascular risk markers, strongly supporting its systemic nature beyond atopic/allergic association.
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http://dx.doi.org/10.1038/s41598-017-09207-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562859PMC
August 2017

A Sensitive IHC Method for Monitoring Autophagy-Specific Markers in Human Tumor Xenografts.

J Biomark 2016 10;2016:1274603. Epub 2016 May 10.

Department of Molecular Pathology, Takeda Pharmaceuticals International Co., Cambridge, MA 02139, USA.

Objective. Use of tyramide signal amplification (TSA) to detect autophagy biomarkers in formalin fixed and paraffin embedded (FFPE) xenograft tissue. Materials and Methods. Autophagy marker regulation was studied in xenograft tissues using Amp HQ IHC and standard IHC methods. Results. The data demonstrate the feasibility of using high sensitivity TSA IHC assays to measure low abundant autophagy markers in FFPE xenograft tissue.
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http://dx.doi.org/10.1155/2016/1274603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877488PMC
June 2016

Cerebral complement C1q activation in chronic Toxoplasma infection.

Brain Behav Immun 2016 Nov 22;58:52-56. Epub 2016 Apr 22.

Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933, USA. Electronic address:

Exposure to the neurotropic parasite, Toxoplasma gondii, causes significant brain and behavioral anomalies in humans and other mammals. Understanding the cellular mechanisms of T. gondii-generated brain pathologies would aid the advancement of novel strategies to reduce disease. Complement factor C1q is part of a classic immune pathway that functions peripherally to tag and remove infectious agents and cellular debris from circulation. In the developing and adult brain, C1q modifies neuronal architecture through synapse marking and pruning. T. gondii exposure and complement activation have both been implicated in the development of complex brain disorders such as schizophrenia. Thus, it seems logical that mechanistically, the physiological pathways associated with these two factors are connected. We employed a rodent model of chronic infection to investigate the extent to which cyst presence in the brain triggers activation of cerebral C1q. Compared to uninfected mice, cortical C1q was highly expressed at both the RNA and protein levels in infected animals bearing a high cyst burden. In these mice, C1q protein localized to cytoplasm, adjacent to GFAP-labeled astrocytes, near degenerating cysts, and in punctate patterns along processes. In summary, our results demonstrated an upregulation of cerebral C1q in response to latent T. gondii infection. Our data preliminarily suggest that this complement activity may aid in the clearance of this parasite from the CNS and in so doing, have consequences for the connectivity of neighboring cells and synapses.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5067173PMC
http://dx.doi.org/10.1016/j.bbi.2016.04.009DOI Listing
November 2016

Rapid determination and chemical change tracking of benzoyl peroxide in wheat flour by multi-step IR macro-fingerprinting.

Spectrochim Acta A Mol Biomol Spectrosc 2016 Feb 24;154:123-129. Epub 2015 Oct 24.

College of Food Science & Technology, Shanghai Ocean University, Shanghai 201306, PR China. Electronic address:

BPO is often added to wheat flour as flour improver, but its excessive use and edibility are receiving increasing concern. A multi-step IR macro-fingerprinting was employed to identify BPO in wheat flour and unveil its changes during storage. BPO contained in wheat flour (<3.0 mg/kg) was difficult to be identified by infrared spectra with correlation coefficients between wheat flour and wheat flour samples contained BPO all close to 0.98. By applying second derivative spectroscopy, obvious differences among wheat flour and wheat flour contained BPO before and after storage in the range of 1500-1400 cm(-1) were disclosed. The peak of 1450 cm(-1) which belonged to BPO was blue shifted to 1453 cm(-1) (1455) which belonged to benzoic acid after one week of storage, indicating that BPO changed into benzoic acid after storage. Moreover, when using two-dimensional correlation infrared spectroscopy (2DCOS-IR) to track changes of BPO in wheat flour (0.05 mg/g) within one week, intensities of auto-peaks at 1781 cm(-1) and 669 cm(-1) which belonged to BPO and benzoic acid, respectively, were changing inversely, indicating that BPO was decomposed into benzoic acid. Moreover, another autopeak at 1767 cm(-1) which does not belong to benzoic acid was also rising simultaneously. By heating perturbation treatment of BPO in wheat flour based on 2DCOS-IR and spectral subtraction analysis, it was found that BPO in wheat flour not only decomposed into benzoic acid and benzoate, but also produced other deleterious substances, e.g., benzene. This study offers a promising method with minimum pretreatment and time-saving to identify BPO in wheat flour and its chemical products during storage in a holistic manner.
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http://dx.doi.org/10.1016/j.saa.2015.10.017DOI Listing
February 2016

An Ep-ICD based index is a marker of aggressiveness and poor prognosis in thyroid carcinoma.

PLoS One 2012 25;7(9):e42893. Epub 2012 Sep 25.

Alex and Simona Shnaider Laboratory in Molecular Oncology, Department of Pathology & Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.

Background: Nuclear accumulation of the intracellular domain of epithelial cell adhesion molecule (Ep-ICD) in tumor cells was demonstrated to predict poor prognosis in thyroid carcinoma patients in our earlier study. Here, we investigated the clinical significance of Ep-ICD subcellular localization index (ESLI) in distinguishing aggressive papillary thyroid carcinoma (PTC) from non-aggressive cases.

Methods: Using domain specific antibodies against the intracellular (Ep-ICD) and extracellular (EpEx) domains of epithelial cell adhesion molecule, 200 archived tissues from a new cohort of patients with benign thyroid disease as well as malignant aggressive and non aggressive PTC were analyzed by immunohistochemistry (IHC). ESLI was defined as sum of the IHC scores for accumulation of nuclear and cytoplasmic Ep-ICD and loss of membranous EpEx; ESLI = [Ep-ICD(nuc) + Ep-ICD(cyt) + loss of membranous EpEx].

Results: For the benign thyroid tissues, non-aggressive PTC and aggressive PTC, the mean ESLI scores were 4.5, 6.7 and 11 respectively. Immunofluorescence double staining confirmed increased nuclear Ep-ICD accumulation and decreased membrane EpEx expression in aggressive PTC. Receiver-operating characteristic (ROC) curve analysis showed an area under the curve (AUC) of 0.841, 70.2% sensitivity and 83.9% specificity for nuclear Ep-ICD for differentiating aggressive PTC from non-aggressive PTC. ESLI distinguished aggressive PTC from non-aggressive cases with improved AUC of 0.924, 88.4% sensitivity and 85.5% specificity. Our study confirms nuclear accumulation of Ep-ICD and loss of membranous EpEx occurs in aggressive PTC underscoring the potential of Ep-ICD and ESLI to serve as diagnostic markers for aggressive PTC. Kaplan Meier survival analysis revealed significantly reduced disease free survival (DFS) for ESLI positive (cutoff >10) PTC (p<0.05), mean DFS=133 months as compared to 210 months for patients who did not show positive ESLI.

Conclusion: ESLI scoring improves the identification of aggressive PTC and thereby may serve as a useful index for defining aggressiveness and poor prognosis among PTC patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042893PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458098PMC
April 2013

Alteration of forkhead box O (foxo4) acetylation mediates apoptosis of podocytes in diabetes mellitus.

PLoS One 2011 17;6(8):e23566. Epub 2011 Aug 17.

Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, New York, United States of America.

The number of kidney podocytes is reduced in diabetic nephropathy. Advanced glycation end products (AGEs) accumulate in patients with diabetes and promote the apoptosis of podocyte by activating the forkhead box O4 (Foxo4) transcription factor to increase the expression of a pro-apoptosis gene, Bcl2l11. Using chromatin immunoprecipitation we demonstrate that AGE-modified bovine serum albumin (AGE-BSA) enhances Foxo4 binding to a forkhead binding element in the promoter of Bcl2lll. AGE-BSA also increases the acetylation of Foxo4. Lysine acetylation of Foxo4 is required for Foxo4 binding and transcription of Bcl2l11 in podocytes treated with AGE-BSA. The expression of a protein deacetylase that targets Foxo4 for deacetylation, sirtuin (Sirt1), is down regulated in cultured podocytes by AGE-BSA treatment and in glomeruli of diabetic patients. SIRT1 over expression in cultured murine podocytes prevents AGE-induced apoptosis. Glomeruli isolated from diabetic db/db mice have increased acetylation of Foxo4, suppressed expression of Sirt1, and increased expression of Bcl2l11 compared to non-diabetic littermates. Together, our data provide evidence that alteration of Foxo4 acetylation and down regulation of Sirt1 expression in diabetes promote podocyte apoptosis. Strategies to preserve Sirt1 expression or reduce Foxo4 acetylation could be used to prevent podocyte loss in diabetes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0023566PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157434PMC
February 2012

Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells.

J Clin Invest 2011 Feb 4;121(2):613-22. Epub 2011 Jan 4.

Department of Dermatology, Kligman Laboratories, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Androgenetic alopecia (AGA), also known as common baldness, is characterized by a marked decrease in hair follicle size, which could be related to the loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from AGA individuals for the presence of hair follicle stem and progenitor cells. Cells expressing cytokeratin15 (KRT15), CD200, CD34, and integrin, α6 (ITGA6) were quantitated via flow cytometry. High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. These KRT15(hi) stem cells were maintained in bald scalp samples. However, CD200(hi)ITGA6(hi) and CD34(hi) cell populations--which both possessed a progenitor phenotype, in that they localized closely to the stem cell-rich bulge area but were larger and more proliferative than the KRT15(hi) stem cells--were markedly diminished. In functional assays, analogous CD200(hi)Itga6(hi) cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of AGA.
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http://dx.doi.org/10.1172/JCI44478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3026732PMC
February 2011

Nuclear and cytoplasmic accumulation of Ep-ICD is frequently detected in human epithelial cancers.

PLoS One 2010 Nov 30;5(11):e14130. Epub 2010 Nov 30.

Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery Program, Mount Sinai Hospital, University of Toronto Medical School, Department of Otolaryngology-Head and Neck Surgery, Toronto, Ontario, Canada.

Background: We previously demonstrated that nuclear and cytoplasmic accumulation of the intracellular domain (Ep-ICD) of epithelial cell adhesion molecule (EpCAM) accompanied by a reciprocal reduction of its extracellular domain (EpEx), occurs in aggressive thyroid cancers. This study was designed to determine whether similar accumulation of Ep-ICD is a common event in other epithelial cancers.

Methodology And Results: Ten epithelial cancers were immunohistochemically analyzed using Ep-ICD and EpEx domain-specific antibodies. The subcellular localization of EpEx and Ep-ICD in the human colon adenocarcinoma cell line CX-1 was observed using immunofluorescence. Nuclear and cytoplasmic Ep-ICD expression was increased in cancers of the breast (31 of 38 tissues, 82%), prostate (40 of 49 tissues, 82%), head and neck (37 of 57 tissues, 65%) and esophagus (17 of 46 tissues, 37%) compared to their corresponding normal tissues that showed membrane localization of the protein. Importantly, Ep-ICD was not detected in the nuclei of epithelial cells in most normal tissues. High nuclear and cytoplasmic Ep-ICD accumulation also occurred in the other six epithelial cancer types analyzed - lung, colon, liver, bladder, pancreatic, and ovarian. A concomitant reduction in membrane EpEx expression was observed in a subset of all cancer types. Receiver operating characteristic curve analysis revealed nuclear Ep-ICD distinguished breast cancers with 82% sensitivity and 100% specificity and prostate cancers with 82% sensitivity and 78% specificity. Similar findings were observed for cytoplasmic accumulation of Ep-ICD in these cancers. We provide clinical evidence of increased nuclear and cytoplasmic Ep-ICD accumulation and a reduction in membranous EpEx in these cancers.

Conclusions: Increased nuclear and cytoplasmic Ep-ICD was observed in all epithelial cancers analyzed and distinguished them from normal tissues with high-sensitivity, specificity, and AUC. Development of a robust high throughput assay for Ep-ICD will facilitate the determination of its diagnostic, prognostic and therapeutic relevance in epithelial cancers.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0014130PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994724PMC
November 2010

The effect of acids on the survival of HIV during drug injection.

J Acquir Immune Defic Syndr 2007 Jun;45(2):144-50

Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA.

Background: HIV epidemics around the world have been linked to injection drug use. In many instances, the injected drugs are acidic. HIV-1 is known to be labile to acids, but its susceptibility to acids in the conditions in which illicit drugs are injected is unknown.

Methods: We have combined data from ethnographic studies of injection drug use practices with laboratory virology to replicate and evaluate the effects of exposure to acids that are experienced during drug preparation and injection on HIV-1 viability.

Results: Short exposures to the acids significantly reduced the likelihood of recovering viable HIV-1 once pH is reduced to 2.3, but acidic solutions did not totally eliminate infectious HIV-1 that might contaminate syringes or solutions being injected, even at the lowest pH tested (pH 1.7).

Conclusions: Acidification of drugs, which is required for dissolving free-base formulations of drugs, can significantly reduce but not eliminate the likelihood that syringes previously used by HIV-1-infected injection drug users infect the next injector. Methamphetamines, which are manufactured under extremely acidic pHs, are unlikely to harbor viable HIV if stored or sold in contaminated injection equipment.
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http://dx.doi.org/10.1097/QAI.0b013e318042aedeDOI Listing
June 2007

Multipolymer solution-phase reactions: application to the Mitsunobu reaction.

J Am Chem Soc 2005 Jan;127(1):52-3

Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045, USA.

The realization of the first polymer-on-polymer Mitsunobu reaction, in which a polymeric phosphine is used simultaneously with a polymeric azodicarboxylate, is reported. This strategy employs the use of soluble oligomers generated from ring-opening methathesis polymerization. 31P NMR analysis revealed that the two polymers were interacting to generate the Mitsunobu products. Application to several substrates, as well as comparison experiments with other polymeric reagents, is described.
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http://dx.doi.org/10.1021/ja045188rDOI Listing
January 2005

Polystyrene-supported triphenylarsine reagents and their use in Suzuki cross-coupling reactions.

J Comb Chem 2004 Nov-Dec;6(6):955-60

Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, People's Republic of China.

Soluble and insoluble polystyrene-bound triphenylarsine reagents have been prepared from 4-styryldiphenylarsine. The utility of these reagents as ligands for palladium in Suzuki cross-coupling reactions is demonstrated. In these applications, the use of polymeric triphenylarsine simplifies the purification of the coupled product and allows for the ligand to be recycled. Furthermore, the soluble polymeric arsine reagent permits the palladium catalyst to be recovered and reused.
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http://dx.doi.org/10.1021/cc049907+DOI Listing
January 2005