Bio


Dr. Albert Chiou is a Clinical Associate Professor of Dermatology. He earned his Bachelor of Science from Stanford University and completed an MPhil in Chemistry, by research, from the University of Cambridge, where he was a Gates Cambridge Scholar. He received his medical degree from Harvard Medical School, where he also completed a joint business degree. Dr. Chiou performed his dermatology residency at Stanford University and served as Chief Resident in his final year. His clinical focus is in medical dermatology.

Dr. Chiou conducts clinical trials investigating new therapies for inflammatory and genetic skin diseases, along with evaluating artificial intelligence-driven decision support approaches for skin cancer and melanoma detection. He is active in supporting institutional research informatics efforts pertinent to clinical research and clinical trials across Stanford Medicine.

Clinical Focus


  • Dermatology
  • Acne
  • Atopic Dermatitis
  • Skin Cancer
  • Dermatologic Surgery
  • Psoriasis

Academic Appointments


Administrative Appointments


  • Faculty Champion for Clinical Research Transformation, Stanford Healthcare, Stanford School of Medicine (2023 - Present)
  • Director, Stanford Skin Innovation and Interventional Research Group (SIIRG) (2019 - Present)
  • Director, Value Based Care, Stanford Department of Dermatology (2021 - Present)

Honors & Awards


  • Medical Dermatology Career Development Award, Dermatology Foundation (2019 - current)
  • Gates Cambridge Scholarship, Gates Cambridge Trust (2007 - 2008)

Boards, Advisory Committees, Professional Organizations


  • Augmented Intelligence Committee, American Academy of Dermatology (2023 - Present)
  • Member, American Academy of Dermatology (2017 - Present)

Professional Education


  • Board Certification: American Board of Dermatology, Dermatology (2017)
  • Chief Resident, Stanford Hospital and Clinics (2017)
  • Residency: Stanford University Dermatology Residency (2017) CA
  • Internship: Santa Clara Valley Medical Center Dept of Medicine (2014) CA
  • MD, MBA, Harvard Medical School (2013)
  • MPhil, University of Cambridge, Chemistry, by Research (2008)
  • BS, Stanford University, Chemistry (2007)

Current Research and Scholarly Interests


I am a clinical researcher interested in evaluating promising new diagnostic paradigms and treatments for serious or poorly treated, chronic skin conditions. My research currently includes:

Therapeutics:

- Treatments for itch from epidermolysis bullosa

- Treatments for chronic wounds for patients with recessive dystrophic epidermolysis bullosa (In collaboration with Dr. Jean Tang and Dr. Peter Marinkovich)

- Treatments for atopic dermatitis, psoriasis, and other inflammatory skin conditions

Diagnostics:

- Artificial intelligence approaches for melanoma and skin cancer early detection

- Imaging mass spectrometry for skin cancer margin analysis and diagnosis

I collaborate with other faculty within the Stanford Skin Innovation and Interventional Research Group (SIIRG) to conduct investigator initiated and sponsored clinical trials seeking to improve care for important dermatologic diseases

Please learn more about our work at: https://siirg.stanford.edu/

Clinical Trials


  • A Study to Evaluate Upadacitinib in Combination With Topical Corticosteroids in Adolescent and Adult Participants With Moderate to Severe Atopic Dermatitis Recruiting

    The objective of this study is to assess the efficacy and safety of upadacitinib combined with topical corticosteroids (TCS) for the treatment of adolescent and adult participants with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

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  • Evaluation of Upadacitinib in Adolescent and Adult Patients With Moderate to Severe Atopic Dermatitis (Eczema) Recruiting

    The objective of this study is to assess the efficacy and safety of upadacitinib for the treatment of adolescent and adult participants with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

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  • SAR231893-LPS15497- "Dupilumab Effect on Sleep in AD Patients" Recruiting

    Primary Objective: To evaluate the effect of dupilumab on sleep quality in adult participants with moderate to severe atopic dermatitis (AD). Secondary Objectives: To evaluate the effect of dupilumab on objective and subjective quantitative sleep parameters, AD related outcomes, and daytime consequences of sleep deprivation. To continue to assess the safety and tolerability throughout the study.

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  • 12-week Study of NFX-179 Gel in Subjects With Epidermal Nevi Not Recruiting

    This study of NFX-179 is an open-label study, evaluating safety, tolerability, pharmacodynamic activity, and the clinical effect in subjects with Epidermal Nevus(ENS). NFX-179 is formulated as a gel for topical administration. NFX-179 has been shown in animal studies and in human extracts to suppress p-ERK with systemic absorption of NFX-179 following topical application to be extremely low, based on serum values observed in animal studies. Primary objectives: - To determine the pharmacodynamic activity of NFX-179 Gel as defined by suppression of phospho-ERK (p-ERK) levels in Target EN in treatment group after 12 weeks of once-daily (QD) application - To determine the safety and tolerability of treatment with NFX-179 Gel 1.50% applied QD for 12 weeks. Secondary objectives: -Clinical effect of NFX-179 Gel 1.5% defined as the percent change in EN volume after 12 weeks of QD application

    Stanford is currently not accepting patients for this trial. For more information, please contact Study Coordinator, 650-206-0647.

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  • A Neurokinin-1 Receptor Antagonist for the Treatment of Pruritus in Patients With Epidermolysis Bullosa Not Recruiting

    To determine if Serlopitant (when taken by mouth) is safe and works on itch in patients aged 13 and above with EB.

    Stanford is currently not accepting patients for this trial. For more information, please contact Clinical Trial Coordinator, 650-721-7149.

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  • Neurokinin-1 Receptor Antagonist for the Treatment of Itch in EB Patients Not Recruiting

    Our goal is to determine whether daily oral administration of VPD-737 (5 mg) is effective and safe in treating moderate to severe pruritus in patients with Epidermolysis Bullosa (EB).

    Stanford is currently not accepting patients for this trial. For more information, please contact Claudia Teng, 725-7152.

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  • Study to Evaluate Adverse Events and Change in Disease Activity With Oral Tablets of Upadacitinib in Adult Participants With Non-Segmental Vitiligo Not Recruiting

    Vitiligo is a common chronic autoimmune disease that causes the body's immune system to attack its own pigment producing skin cells. This study is to evaluate how safe and effective upadacitinib is in participants with non-segmental vitiligo. Adverse effects and change in disease activity will be assessed. Upadacitinib is being evaluated for the treatment of non-segmental vitiligo. The study will enroll approximately 160 participants aged 18-65 with non-segmental vitiligo in 5 treatment arms across 35 sites worldwide. Participants will either receive study drug vs placebo oral tablets once daily (QD) for 24 weeks (Period A). In Period B (up to 52 weeks), participants who received placebo during the first 24 weeks will switch to study drug. Participants who received study drug during the first 24 weeks, will continue to receive study drug. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

    Stanford is currently not accepting patients for this trial.

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All Publications


  • Disparities in dermatology AI performance on a diverse, curated clinical image set. Science advances Daneshjou, R., Vodrahalli, K., Novoa, R. A., Jenkins, M., Liang, W., Rotemberg, V., Ko, J., Swetter, S. M., Bailey, E. E., Gevaert, O., Mukherjee, P., Phung, M., Yekrang, K., Fong, B., Sahasrabudhe, R., Allerup, J. A., Okata-Karigane, U., Zou, J., Chiou, A. S. 2022; 8 (32): eabq6147

    Abstract

    An estimated 3 billion people lack access to dermatological care globally. Artificial intelligence (AI) may aid in triaging skin diseases and identifying malignancies. However, most AI models have not been assessed on images of diverse skin tones or uncommon diseases. Thus, we created the Diverse Dermatology Images (DDI) dataset-the first publicly available, expertly curated, and pathologically confirmed image dataset with diverse skin tones. We show that state-of-the-art dermatology AI models exhibit substantial limitations on the DDI dataset, particularly on dark skin tones and uncommon diseases. We find that dermatologists, who often label AI datasets, also perform worse on images of dark skin tones and uncommon diseases. Fine-tuning AI models on the DDI images closes the performance gap between light and dark skin tones. These findings identify important weaknesses and biases in dermatology AI that should be addressed for reliable application to diverse patients and diseases.

    View details for DOI 10.1126/sciadv.abq6147

    View details for PubMedID 35960806

  • A qualitative exploration of the experiences of itch for adults living with epidermolysis bullosa. The British journal of dermatology de Vere Hunt, I., Halley, M., Sum, K., Yekrang, K., Phung, M., Good, J., Linos, E., Chiou, A. S. 1800

    View details for DOI 10.1111/bjd.21031

    View details for PubMedID 35092694

  • Phase 2 Trial of a Neurokinin-1 Receptor Antagonist for the Treatment of Chronic Itch in Epidermolysis Bullosa Patients: A Randomized Clinical Trial. Journal of the American Academy of Dermatology Chiou, A. S., Choi, S., Barriga, M., Dutt-Singkh, Y., Solis, D. C., Nazaroff, J., Bailey-Healy, I., Li, S., Shu, K., Joing, M., Kwon, P., Tang, J. Y. 2019

    Abstract

    BACKGROUND: Chronic pruritus causes major morbidity in epidermolysis bullosa (EB). The substance P-neurokinin 1 receptor (SP-NK1) pathway is a promising target for treating EB-related pruritus.OBJECTIVE: To evaluate the safety and efficacy of oral NK1 receptor antagonist serlopitant in treating moderate-severe pruritus in EB.METHODS: 14 patients were randomized to serlopitant or placebo for 8 weeks, followed by a 4-week washout and optional open-label extension. The primary endpoint was change in itch as measured by a numeric rating scale (NRS). Secondary endpoints were change in: (1) itch during dressing changes and (2) wound size.RESULTS: We observed greater itch reduction with serlopitant, equivalent to a 0.64-point comparative reduction on the 11-point NRS by week 8, though this failed to meet statistical significance (p=0.11). More serlopitant patients achieved ≥3-point reduction compared to placebo (43% vs. 14%, p=0.35). In post hoc analysis excluding one subject with a concurrent seborrheic dermatitis flare, serlopitant achieved significantly greater median itch reduction from baseline by week 4 (-2 points vs. 0, p=0.01). We observed no statistically significant differences in secondary endpoints. Serlopitant was well-tolerated.LIMITATIONS: Small sample size due to disease rarity CONCLUSION: The potential itch reduction with serlopitant observed in this trial will be pursued by a larger powered trial (NCT03836001).

    View details for DOI 10.1016/j.jaad.2019.09.014

    View details for PubMedID 31541747

  • Adult-onset inflammatory linear verrucous epidermal nevus successfully treated with intralesional steroid. JAAD case reports Johnson, A. N., Sum, K., Rieger, K. E., Chiou, A. S., Li, D. J. 2024; 46: 5-7

    View details for DOI 10.1016/j.jdcr.2024.02.001

    View details for PubMedID 38445192

  • Noninvasive Detection of Skin Cancer by Imprint Desorption Electrospray Ionization Mass Spectrometry Imaging. Analytical chemistry Meng, Y., Chiou, A. S., Aasi, S. Z., See, N. A., Song, X., Zare, R. N. 2023

    Abstract

    We report a technique for the noninvasive detection of skin cancer by imprint desorption electrospray ionization mass spectrometry imaging (DESI-MSI) using a transfer agent that is pressed against the tissue of interest. By noninvasively pressing a tape strip against human skin, metabolites, fatty acids, and lipids on the skin surface are transferred to the tape with little spatial distortion. Running DESI-MSI on the tape strip provides chemical images of the molecules on the skin surface, which are valuable for distinguishing cancer from healthy skin. Chemical components of the tissue imprint on the tape strip and the original basal cell carcinoma (BCC) section from the mass spectra show high consistency. By comparing MS images (about 150-μm resolution) of same molecules from the tape strip and from the BCC section, we confirm that chemical patterns are successfully transferred to the tape stripe. We also used the technique to distinguish cherry angiomas from normal human skin by comparing the molecular patterns from a tape strip. These results demonstrate the potential of the imprint DESI-MSI technique for the noninvasive detection of skin cancers as well as other skin diseases before and during clinical surgery.

    View details for DOI 10.1021/acs.analchem.3c04918

    View details for PubMedID 38155587

  • Association between yearlong air pollution and moderate-severe atopic dermatitis: A United States cross-sectional claims analysis. JAAD international Trinh, P., Allerup, J. A., Li, S., Ko, J., Chen, J., Linos, E., Chiou, A. S. 2023; 13: 4-6

    View details for DOI 10.1016/j.jdin.2023.04.017

    View details for PubMedID 37592975

  • Development of a digital tool for home-based monitoring of skin disease for older adults. Skin health and disease van Egmond, S., Cai, Z. R., Nava, V., Joy de Vere Hunt, I., Rapaport, B. R., Ko, J., Chiou, A. S., Sarin, K., Tang, J., Zhang, L., Linos, E. 2023; 3 (5): e235

    Abstract

    We developed a digital tool for home-based monitoring of skin disease, our digital tool. In the current observational pilot study, we found that DORA is feasible to use in practice, as it has a high patient compliance, retention and satisfaction. Clinicans rated the photos generally good quality or perfect quality. These results show that the digital health tool DORA can easily be used by patients to send photos to their dermatologist, which could reduce unnecessary clinical visits. It may also be used in other settings where digital literacy barriers and unequal access to dermatologists contribute to healthcare disparities.

    View details for DOI 10.1002/ski2.235

    View details for PubMedID 37799368

    View details for PubMedCentralID PMC10549824

  • Dupilumab significantly improves sleep in adults with atopic dermatitis: results from the 12-week placebo-controlled period of the 24-week phase 4 randomized double-blinded placebo-controlled DUPISTAD study. The British journal of dermatology Merola, J. F., Chiou, A. S., During, E., Costanzo, A., Foley, P., Alfalasi, A., Gogate, S., Pinter, A., Dodiuk-Gad, R., Simon, D., Tauber, M., Weller, R., Pereyra-Rodriguez, J. J., Ardeleanu, M., Wu, J., Ozturk, Z. E. 2023

    Abstract

    Sleep disturbance is a prominent symptom of atopic dermatitis (AD) and can result in insomnia, daytime fatigue, drowsiness, reduced productivity, and impaired quality of life (QoL).The DUPISTAD (Dupilumab Effect on Sleep in AD Patients) phase 4 randomized double-blinded placebo-controlled study evaluated the impact of dupilumab treatment on sleep and other patient- and physician-reported outcomes.Adults with moderate-to-severe AD were randomized 2:1 to dupilumab 300 mg once every 2 weeks (q2w) or placebo for 12 weeks; concomitant topical corticosteroids were permitted. Patients subsequently entered an open-label phase and received dupilumab 300 mg q2w for a further 12 weeks. The primary endpoint was percentage change from baseline to Week 12 in sleep quality, assessed using a novel numeric rating scale (NRS). Secondary and exploratory endpoints included percent change in peak pruritus NRS (PP NRS), change in SCORing Atopic Dermatitis (SCORAD), SCORAD sleep visual analog scale (VAS), Eczema Area and Severity Index, Patient Reported Outcomes Measurement Information System (PROMIS) sleep-related impairment T-score, and the Epworth Sleepiness Scale (ESS). Sleep diary and wrist actigraphy measurements were recorded throughout the study.In total, 127 patients received dupilumab and 61 placebo. Demographic and baseline disease characteristics were balanced between groups. Sleep quality NRS significantly improved in dupilumab-treated patients by Week 12 versus placebo (LSMD-15.5%, P<0.001). PP NRS (LSMD -27.9%, P<0.001), SCORAD (LSMD -15.1, P<0.001), SCORAD sleep VAS (LSMD -2.1, P<0.001), and PROMIS T-score (LSMD -3.6, P<0.001) were also significantly improved at Week 12 with dupilumab versus placebo. The overall percentage of patients reporting treatment-emergent adverse events was lower in the dupilumab group (56.7%) than in the placebo group (67.2%).Dupilumab significantly improved sleep quality and perception of sleep continuity, itch, metrics of AD severity, and QoL in adults with moderate-to-severe AD, with an acceptable safety profile versus placebo.ClinicalTrials.gov: NCT04033367.

    View details for DOI 10.1093/bjd/ljad284

    View details for PubMedID 37562034

  • Best Practices for Clinical Skin Image Acquisition in Translational Artificial Intelligence Research. The Journal of investigative dermatology Phung, M., Muralidharan, V., Rotemberg, V., Novoa, R. A., Chiou, A. S., Sadée, C. Y., Rapaport, B., Yekrang, K., Bitz, J., Gevaert, O., Ko, J. M., Daneshjou, R. 2023; 143 (7): 1127-1132

    Abstract

    Recent advances in artificial intelligence research have led to an increase in the development of algorithms for detecting malignancies from clinical and dermoscopic images of skin diseases. These methods are dependent on the collection of training and testing data. There are important considerations when acquiring skin images and data for translational artificial intelligence research. In this paper, we discuss the best practices and challenges for light photography image data collection, covering ethics, image acquisition, labeling, curation, and storage. The purpose of this work is to improve artificial intelligence for malignancy detection by supporting intentional data collection and collaboration between subject matter experts, such as dermatologists and data scientists.

    View details for DOI 10.1016/j.jid.2023.02.035

    View details for PubMedID 37353282

  • Development and Clinical Evaluation of an Artificial Intelligence Support Tool for Improving Telemedicine Photo Quality. JAMA dermatology Vodrahalli, K., Ko, J., Chiou, A. S., Novoa, R., Abid, A., Phung, M., Yekrang, K., Petrone, P., Zou, J., Daneshjou, R. 2023

    Abstract

    Importance: Telemedicine use accelerated during the COVID-19 pandemic, and skin conditions were a common use case. However, many images submitted may be of insufficient quality for making a clinical determination.Objective: To determine whether an artificial intelligence (AI) decision support tool, a machine learning algorithm, could improve the quality of images submitted for telemedicine by providing real-time feedback and explanations to patients.Design, Setting, and Participants: This quality improvement study with an AI performance component and single-arm clinical pilot study component was conducted from March 2020 to October 2021. After training, the AI decision support tool was tested on 357 retrospectively collected telemedicine images from Stanford telemedicine from March 2020 to June 2021. Subsequently, a single-arm clinical pilot study was conducted to assess feasibility with 98 patients in the Stanford Department of Dermatology across 2 clinical sites from July 2021 to October 2021. For the clinical pilot study, inclusion criteria for patients included being adults (aged ≥18 years), presenting to clinic for a skin condition, and being able to photograph their own skin with a smartphone.Interventions: During the clinical pilot study, patients were given a handheld smartphone device with a machine learning algorithm interface loaded and were asked to take images of any lesions of concern. Patients were able to review and retake photos prior to submitting, so each submitted photo met the patient's assumed standard of clinical acceptability. A machine learning algorithm then gave the patient feedback on whether the image was acceptable. If the image was rejected, the patient was provided a reason by the AI decision support tool and allowed to retake the photos.Main Outcomes and Measures: The main outcome of the retrospective image analysis was the receiver operator curve area under the curve (ROC-AUC). The main outcome of the clinical pilot study was the image quality difference between the baseline images and the images approved by AI decision support.Results: Of the 98 patients included, the mean (SD) age was 49.8 (17.6) years, and 50 (51%) of the patients were male. On retrospective telemedicine images, the machine learning algorithm effectively identified poor-quality images (ROC-AUC of 0.78) and the reason for poor quality (blurry ROC-AUC of 0.84; lighting issues ROC-AUC of 0.70). The performance was consistent across age and sex. In the clinical pilot study, patient use of the machine learning algorithm was associated with improved image quality. An AI algorithm was associated with reduction in the number of patients with a poor-quality image by 68.0%.Conclusions and Relevance: In this quality improvement study, patients use of the AI decision support with a machine learning algorithm was associated with improved quality of skin disease photographs submitted for telemedicine use.

    View details for DOI 10.1001/jamadermatol.2023.0091

    View details for PubMedID 36920380

  • Evaluation of diagnosis diversity in artificial intelligence datasets: a scoping review. The British journal of dermatology Chen, M. L., Rotemberg, V., Lester, J. C., Novoa, R. A., Chiou, A. S., Daneshjou, R. 2023; 188 (2): 292-294

    View details for DOI 10.1093/bjd/ljac047

    View details for PubMedID 36763858

  • Long-term safety and efficacy of gene-corrected autologous keratinocyte grafts for recessive dystrophic epidermolysis bullosa. Orphanet journal of rare diseases So, J. Y., Nazaroff, J., Iwummadu, C. V., Harris, N., Gorell, E. S., Fulchand, S., Bailey, I., McCarthy, D., Siprashvili, Z., Marinkovich, M. P., Tang, J. Y., Chiou, A. S. 2022; 17 (1): 377

    Abstract

    BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating blistering genodermatosis caused by mutations in the COL7A1 gene, which encodes for type VII collagen and is necessary for dermal-epidermal adhesion and integrity. Disease manifestations include severe and debilitating wounds, aggressive squamous cell carcinomas, and premature death; however, there are currently no approved therapies. This Phase 1/2a, open-label study evaluated the long-term efficacy and safety of gene-corrected autologous keratinocyte grafts (EB-101) for chronic RDEB wounds.METHODS: Autologous keratinocytes were harvested from participants with severe RDEB, transduced with a retrovirus containing the full-length COL7A1 gene, and grown into 5*7cm (35 cm2) sheets. Gene-corrected keratinocyte sheets were then transplanted onto chronic RDEB wounds present for≥12weeks.RESULTS: Seven adult participants with severe RDEB were grafted with six sheets each (42 total sheets) onto wounds and followed for a mean of 5.9years (range 4-8years). Long-term improvements in wound healing and symptoms were observed. At year five, 70% (21/30) of treated sites demonstrated≥50% wound healing compared to baseline by investigator global assessment. No sites with≥50% wound healing were painful or pruritic, compared to 67% (6/9) of sites with<50% wound healing (p<0.001) at year five. Grafts were well-tolerated throughout long-term follow-up. No serious adverse events related to treatment were reported over a mean of 5.9years of follow-up. No persistent systemic autoimmunity against type VII collagen or replication-competent retrovirus infections were identified, and no participants developed squamous cell carcinomas related to treatment during long-term follow-up.CONCLUSIONS: Treatment with EB-101 appears safe and efficacious, and produces long-term improvements in wound healing, pain, and itch for RDEB patients. Results from the Phase 3 randomized controlled trial are forthcoming.TRIAL REGISTRATION: ClinicalTrials.gov, NCT01263379. Registered December 15, 2010. https://clinicaltrials.gov/ct2/show/NCT01263379.

    View details for DOI 10.1186/s13023-022-02546-9

    View details for PubMedID 36253825

  • Asymptomatic, Microscopic Hematuria in Epidermolysis Bullosa: A Single Center Retrospective Case Series. Journal of the American Academy of Dermatology Betancourt, N. J., Sum, K., Gorell, E. S., Tang, J. Y., Chiou, A. S. 2022

    View details for DOI 10.1016/j.jaad.2022.08.030

    View details for PubMedID 36007691

  • A global, cross-sectional survey of patient-reported outcomes, disease burden, and quality of life in epidermolysis bullosa simplex. Orphanet journal of rare diseases So, J. Y., Fulchand, S., Wong, C. Y., Li, S., Nazaroff, J., Gorell, E. S., de Souza, M. P., Murrell, D. F., Teng, J. M., Chiou, A. S., Tang, J. Y. 2022; 17 (1): 270

    Abstract

    Epidermolysis bullosa simplex (EBS) comprises a group of rare, blistering genodermatoses. Prior work has been limited by small sample sizes, and much remains unexplored about the disease burden and health-related quality of life (QOL) of patients with EBS. The aim of this study was to characterize the most common patient-reported clinical manifestations and the health-related impact of QOL in EBS, and to examine differences in disease burden by age.Patients with a diagnosis of epidermolysis bullosa (EB) or their caregivers completed a one-time online survey administered by EBCare, an international online EB registry. Survey data from respondents self-reporting a diagnosis of EBS were analyzed for clinical and wound manifestations, medication use, and QOL (using Quality of Life in Epidermolysis Bullosa [QOLEB] scores). Differences across age groups were assessed using Kruskal-Wallis and Fisher's exact tests.There were 214 survey respondents with EBS. The mean age was 32.8 years (standard deviation = 19.2). Many respondents reported blisters (93%), recurrent wounds (89%), pain (74%), chronic wounds (59%), itch (55%), and difficulty walking (44%). Mean QOLEB score was 14.7 (standard deviation = 7.5) indicating a "moderate" impact on QOL, and 12% of respondents required regular use of opiates. Findings were consistent in subgroup analyses restricted to respondents with diagnostic confirmation via genetic testing or skin biopsy (n = 63 of 214). Age-stratified analyses revealed differences in disease burden: younger respondents were more likely to self-report severe disease (24% vs. 19% vs. 5% for respondents aged 0-9 vs. 10-17 vs. 18 + , p = 0.001), failure to thrive (9% vs. 15% vs. 3%, p = 0.02), and use of gastrostomy tubes (15% vs. 12% vs. 1%, p < 0.001) and topical antibiotics (67% vs. 69% vs. 34%, p < 0.001), while older respondents were more likely to be overweight or obese (6% vs. 0% vs. 51%, p < 0.001) and have difficulty walking (24% vs. 46% vs. 48%, p = 0.04).In the largest international cross-sectional survey of EBS patients conducted, respondents reported extensive disease burden including significant wounding, pain, itch, difficulty walking, and impact on QOL. Age stratified disease manifestations. These findings suggest significant unmet need, and treatment and counseling for EBS patients should consider age-specific differences.

    View details for DOI 10.1186/s13023-022-02433-3

    View details for PubMedID 35841105

  • Efficacy and Safety of Upadacitinib in Patients With Moderate to Severe Atopic Dermatitis: Analysis of Follow-up Data From the Measure Up 1 and Measure Up 2 Randomized Clinical Trials. JAMA dermatology Simpson, E. L., Papp, K. A., Blauvelt, A., Chu, C. Y., Hong, H. C., Katoh, N., Calimlim, B. M., Thyssen, J. P., Chiou, A. S., Bissonnette, R., Stein Gold, L. F., Wegzyn, C., Hu, X., Liu, M., Liu, J., Tenorio, A. R., Chu, A. D., Guttman-Yassky, E. 2022

    Abstract

    Primary results from the Measure Up 1 and Measure Up 2 studies demonstrated upadacitinib efficacy and safety through 16 weeks in patients with atopic dermatitis. Longer-term outcomes remain unknown.To evaluate long-term (52 weeks) efficacy and safety of upadacitinib treatment in patients with atopic dermatitis.Measure Up 1 and Measure Up 2 are ongoing double-blind, placebo-controlled, replicate phase 3 randomized clinical trials that include adults and adolescents with moderate to severe atopic dermatitis at 151 and 154 centers, respectively. Cutoffs for this analysis were December 21, 2020 (Measure Up 1), and January 15, 2021 (Measure Up 2).Patients were randomized 1:1:1 to receive once-daily oral upadacitinib 15 mg, 30 mg, or placebo. At week 16, patients randomized at baseline to receive upadacitinib 15 mg (273 and 260 patients in Measure Up 1 and Measure Up 2, respectively) and 30 mg (270 and 268 patients) continued assigned treatment; placebo-treated patients were rerandomized 1:1 to receive upadacitinib 15 mg (121 and 120 patients in Measure Up 1 and Measure Up 2, respectively) or 30 mg (123 and 121 patients) in a double-blinded manner.Safety and efficacy, including 75% improvement in the Eczema Area and Severity Index and Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement, were assessed.Measure Up 1 and Measure Up 2 included a total of 1609 patients (mean [SD] age, 33.8 [15.6] years; 727 women [45.2%]; 882 men [54.8%]). Efficacy at week 16 was maintained through week 52. At week 52, 75% improvement in the Eczema Area and Severity Index was achieved by 82.0% (95% CI, 77.0%-86.9%) and 79.1% (95% CI, 73.9%-84.4%) of patients continuing the 15-mg dose and 84.9% (95% CI, 80.3%-89.5%) and 84.3% (95% CI, 79.6%-89.0%) of patients continuing the 30-mg dose (for Measure Up 1 and Measure Up 2, respectively); Validated Investigator Global Assessment for Atopic Dermatitis score of clear (0) or almost clear (1) with 2 or greater grades of improvement was achieved by 59.2% (95% CI, 52.9%-65.5%) and 52.6% (95% CI, 46.2%-59.1%) and 62.5% (95% CI, 56.3%-68.7%) and 65.1% (95% CI, 58.9%-71.2%) of patients in the Measure Up 1 and Measure Up 2 studies, respectively. Treatment discontinuation due to adverse events was low overall but was slightly higher for the upadacitinib 30-mg dose. Both upadacitinib doses were well tolerated with no new safety signals.In this analysis of follow-up data from 2 randomized clinical trials, longer-term treatment of adolescents and adults with moderate to severe atopic dermatitis with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 52 weeks.ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1) and NCT03607422 (Measure Up 2).

    View details for DOI 10.1001/jamadermatol.2022.0029

    View details for PubMedID 35262646

  • Histopathologic correlation of skin manifestations of multisystemic inflammatory syndrome in adults (MIS-A) associated with SARS-CoV-2 infection. JAAD case reports So, N. A., So, J., Centkowski, S., Rana, J., Aleshin, M., Kwong, B. Y., Rieger, K., Zaba, L. C., Chiou, A. S. 2021

    View details for DOI 10.1016/j.jdcr.2021.06.031

    View details for PubMedID 34405113

  • A systematic literature review of the disease burden in patients with recessive dystrophic epidermolysis bullosa. Orphanet journal of rare diseases Tang, J. Y., Marinkovich, M. P., Lucas, E., Gorell, E., Chiou, A., Lu, Y., Gillon, J., Patel, D., Rudin, D. 2021; 16 (1): 175

    Abstract

    BACKGROUND/OBJECTIVE: Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic collagen disorder characterized by skin fragility leading to blistering, wounds, and scarring. There are currently no approved curative therapies. The objective of this manuscript is to provide a comprehensive literature review of the disease burden caused by RDEB.METHODS: A systematic literature review was conducted in MEDLINE and Embase in accordance with PRISMA guidelines. Observational and interventional studies on the economic, clinical, or humanistic burden of RDEB were included.RESULTS: Sixty-five studies were included in the review. Patients had considerable wound burden, with 60% reporting wounds covering more than 30% of their body. Increases in pain and itch were seen with larger wound size. Chronic wounds were larger and more painful than recurrent wounds. Commonly reported symptoms and complications included lesions and blistering, anemia, nail dystrophy and loss, milia, infections, musculoskeletal contractures, strictures or stenoses, constipation, malnutrition/nutritional problems, pseudosyndactyly, ocular manifestations, and dental caries. Many patients underwent esophageal dilation (29-74%; median dilations, 2-6) and gastrostomy tube placement (8-58%). In the severely affected population, risk of squamous cell carcinoma (SCC) was 76% and mortality from SCC reached 84% by age 40. Patients with RDEB experienced worsened quality of life (QOL), decreased functioning and social activities, and increased pain and itch when compared to other EB subtypes, other skin diseases, and the general population. Families of patients reported experiencing high rates of burden including financial burden (50-54%) and negative impact on private life (79%). Direct medical costs were high, though reported in few studies; annual payer-borne total medical costs in Ireland were $84,534 and annual patient-borne medical costs in Korea were $7392. Estimated annual US costs for wound dressings ranged from $4000 to $245,000. Patients spent considerable time changing dressings: often daily (13-54% of patients) with up to three hours per change (15-40%).CONCLUSION: Patients with RDEB and their families/caregivers experience significant economic, humanistic, and clinical burden. Further research is needed to better understand the costs of disease, how the burden of disease changes over the patient lifetime and to better characterize QOL impact, and how RDEB compares with other chronic, debilitating disorders.

    View details for DOI 10.1186/s13023-021-01811-7

    View details for PubMedID 33849616

  • TrueImage: A Machine Learning Algorithm to Improve the Quality of Telehealth Photos. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing Vodrahalli, K., Daneshjou, R., Novoa, R. A., Chiou, A., Ko, J. M., Zou, J. 2021; 26: 220–31

    Abstract

    Telehealth is an increasingly critical component of the health care ecosystem, especially due to the COVID-19 pandemic. Rapid adoption of telehealth has exposed limitations in the existing infrastructure. In this paper, we study and highlight photo quality as a major challenge in the telehealth workflow. We focus on teledermatology, where photo quality is particularly important; the framework proposed here can be generalized to other health domains. For telemedicine, dermatologists request that patients submit images of their lesions for assessment. However, these images are often of insufficient quality to make a clinical diagnosis since patients do not have experience taking clinical photos. A clinician has to manually triage poor quality images and request new images to be submitted, leading to wasted time for both the clinician and the patient. We propose an automated image assessment machine learning pipeline, TrueImage, to detect poor quality dermatology photos and to guide patients in taking better photos. Our experiments indicate that TrueImage can reject ~50% of the sub-par quality images, while retaining ~80% of good quality images patients send in, despite heterogeneity and limitations in the training data. These promising results suggest that our solution is feasible and can improve the quality of teledermatology care.

    View details for PubMedID 33691019

  • TrueImage: A Machine Learning Algorithm to Improve the Quality of Telehealth Photos Vodrahalli, K., Daneshjou, R., Novoa, R. A., Chiou, A., Ko, J. M., Zou, J., Altman, R. B., Dunker, A. K., Hunter, L., Ritchie, M. D., Murray, T., Klein, T. E. WORLD SCIENTIFIC PUBL CO PTE LTD. 2021: 220-231
  • Prevalence of Potentially Allergenic Ingredients in Products Labeled for Eczema Care. Journal of the American Academy of Dermatology Schwartz, B. L., Honari, G., Chiou, A. S., Ko, J., Sarin, K. Y., Chen, J. K. 2021

    View details for DOI 10.1016/j.jaad.2021.05.038

    View details for PubMedID 34058279

  • Telehealth for Older Adults with Skin Disease: A Qualitative Exploration of Dermatologists' Experiences & Recommendations for Improving Care. The British journal of dermatology de Vere Hunt, I., van Egmond, S., Nava, V., Khodosh, R., Lester, J., Chiou, A. S., Linos, E. 2021

    Abstract

    The COVID-19 pandemic accelerated the use of telehealth, defined as the delivery of health care via remote technologies1 , with widespread adoption of live-interactive video visits across the US.2 3 4 Yet, it is important to avoid exacerbating healthcare disparities for vulnerable populations such as older adults, who traditionally have more technological literacy barriers.5 6 Our aim was to explore dermatologists' experiences of using telehealth with older adults, in order to identify and summarise recommendations to improve telehealth care.

    View details for DOI 10.1111/bjd.20891

    View details for PubMedID 34773643

  • Bridging to a selective Janus kinase 1 inhibitor in severe atopic dermatitis: An instructive case with upadacitinib. JAAD case reports Nguyen, J., Chen, J. K., Honari, G., Pol-Rodriguez, M., Ko, J. M., Chiou, A. S. 2021; 7: 65–67

    View details for DOI 10.1016/j.jdcr.2020.10.023

    View details for PubMedID 33354610

  • Pernio-like eruption associated with COVID-19 in skin of color. JAAD case reports Daneshjou, R., Rana, J., Dickman, M., Yost, J. M., Chiou, A., Ko, J. 2020; 6 (9): 892–97

    View details for DOI 10.1016/j.jdcr.2020.07.009

    View details for PubMedID 32835046

  • An exploratory, open-label, investigator-initiated study of interleukin-17A (IL-17A) blockade in patients with moderate to severe papulopustular rosacea. The British journal of dermatology Kumar, A. M., Chiou, A. S., Shih, Y. H., Li, S., Chang, A. L. 2020

    Abstract

    Currently, few systemic medications are effective for rosacea.1 Recent research has shown elevation of interleukin (IL)-17A in rosacea.2,3 To assess if the IL-17A inhibitor,4, 5 secukinumab, could improve moderate to severe papulopustular rosacea (PPR), an exploratory, open-label, single-arm investigator initiated clinical trial in adults with moderate to severe PPR was performed after Stanford Human Subjects Panel approval.

    View details for DOI 10.1111/bjd.19172

    View details for PubMedID 32364247

  • Dupilumab Treatment of Nummular Dermatitis: A Retrospective Cohort Study. Journal of the American Academy of Dermatology Choi, S. n., Zhu, G. A., Lewis, M. A., Honari, G. n., Chiou, A. S., Ko, J. n., Chen, J. K. 2020

    View details for DOI 10.1016/j.jaad.2019.12.054

    View details for PubMedID 31923445

  • Dupilumab for occupational irritant hand dermatitis in a nonatopic individual: A case report. JAAD case reports Zhu, G. A., Honari, G. n., Ko, J. M., Chiou, A. S., Chen, J. K. 2020; 6 (4): 296–98

    View details for DOI 10.1016/j.jdcr.2020.02.010

    View details for PubMedID 32258302

    View details for PubMedCentralID PMC7109358

  • Inflammatory alopecia in patients on dupilumab: a retrospective cohort study at an academic institution. Journal of the European Academy of Dermatology and Venereology : JEADV Zhu, G. A., Kang, K. J., Chen, J. K., Novoa, R. A., Brown, R. A., Chiou, A. S., Ko, J. M., Honari, G. 2019

    Abstract

    Dupilumab targets IL-4Ralpha and is used for moderate-to-severe atopic dermatitis (AD). Prior reports have described new alopecia areata (AA),1 flaring of prior AA,2 as well as improvement or resolution of AA3 in patients treated with dupilumab. We conducted a retrospective cohort study to describe the natural history of prior or new inflammatory alopecia in patients on dupilumab.

    View details for DOI 10.1111/jdv.16094

    View details for PubMedID 31737955

  • Phase 1/2a clinical trial of gene-corrected autologous cell therapy for recessive dystrophic epidermolysis bullosa. JCI insight Eichstadt, S., Barriga, M., Ponakala, A., Teng, C., Nguyen, N. T., Siprashvili, Z., Nazaroff, J., Gorell, E. S., Chiou, A. S., Taylor, L., Khuu, P., Keene, D. R., Rieger, K., Khosla, R. K., Furukawa, L. K., Lorenz, H. P., Marinkovich, M. P., Tang, J. Y. 2019; 4 (19)

    Abstract

    BACKGROUNDRecessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene and thus lack functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy.METHODSAutologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5 * 7 cm (35 cm2) and were transplanted onto 6 wound sites in each of 7 adult participants (n = 42 sites total) from 2013 to 2017. Participants were followed for 2 to 5 years.RESULTSNo participants experienced any serious related adverse events. Wound healing of 50% or greater by Investigator Global Assessment was present in 95% (36 of 38) of treated wounds versus 0% (0 of 6) of untreated control wounds at 6 months (P < 0.0001). At year 1, 68% (26 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.025). At year 2, 71% (27 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.019).CONCLUSIONC7 expression persisted up to 2 years after treatment in 2 participants. Treated wounds with 50% or greater healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene-corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes.TRIAL REGISTRATIONClinicaltrials.gov identifier: NCT01263379.FUNDINGEpidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH R01 AR055914, Office of Research and Development at the Palo Alto Veteran's Affairs Medical Center, and the Dermatology Foundation.

    View details for DOI 10.1172/jci.insight.130554

    View details for PubMedID 31578311

  • Angiodestructive lymphomatoid papulosis lasting more than 45years. JAAD case reports Lee, G. H., Bae, G. H., Rieger, K. E., Kim, Y. H., Chiou, A. S. 2019; 5 (9): 767–69

    View details for DOI 10.1016/j.jdcr.2019.06.027

    View details for PubMedID 31516992

  • Repeat patch testing in a patient with allergic contact dermatitis improved on dupilumab. JAAD case reports Zhu, G. A., Chen, J. K., Chiou, A., Ko, J., Honari, G. 2019; 5 (4): 336–38

    View details for PubMedID 30989102

  • Assessment of the Development of New Regional Dermatoses in Patients Treated for Atopic Dermatitis With Dupilumab. JAMA dermatology Zhu, G. A., Chen, J. K., Chiou, A. n., Ko, J. n., Honari, G. n. 2019

    View details for PubMedID 31042259

  • Distinguishing malignant from benign microscopic skin lesions using desorption electrospray ionization mass spectrometry imaging PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Margulis, K., Chiou, A. S., Aasi, S. Z., Tibshirani, R. J., Tang, J. Y., Zare, R. N. 2018; 115 (25): 6347–52
  • Distinguishing malignant from benign microscopic skin lesions using desorption electrospray ionization mass spectrometry imaging. Proceedings of the National Academy of Sciences of the United States of America Margulis, K. n., Chiou, A. S., Aasi, S. Z., Tibshirani, R. J., Tang, J. Y., Zare, R. N. 2018

    Abstract

    Detection of microscopic skin lesions presents a considerable challenge in diagnosing early-stage malignancies as well as in residual tumor interrogation after surgical intervention. In this study, we established the capability of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to distinguish between micrometer-sized tumor aggregates of basal cell carcinoma (BCC), a common skin cancer, and normal human skin. We analyzed 86 human specimens collected during Mohs micrographic surgery for BCC to cross-examine spatial distributions of numerous lipids and metabolites in BCC aggregates versus adjacent skin. Statistical analysis using the least absolute shrinkage and selection operation (Lasso) was employed to categorize each 200-µm-diameter picture element (pixel) of investigated skin tissue map as BCC or normal. Lasso identified 24 molecular ion signals, which are significant for pixel classification. These ion signals included lipids observed at m/z 200-1,200 and Krebs cycle metabolites observed at m/z < 200. Based on these features, Lasso yielded an overall 94.1% diagnostic accuracy pixel by pixel of the skin map compared with histopathological evaluation. We suggest that DESI-MSI/Lasso analysis can be employed as a complementary technique for delineation of microscopic skin tumors.

    View details for PubMedID 29866838

  • Localized bullous pemphigoid in a melanoma patient with dual exposure to PD-1 checkpoint inhibition and radiation therapy. JAAD case reports Hirotsu, K. n., Chiou, A. S., Chiang, A. n., Kim, J. n., Kwong, B. Y., Pugliese, S. n. 2017; 3 (5): 404–6

    View details for PubMedID 28884139

  • Cutaneous Neonatal Lupus Arising in an Infant Conceived From an Oocyte Donation Pregnancy JAMA DERMATOLOGY Chiou, A. S., Sun, G., Kim, J., Wang, K. C., Marqueling, A. L. 2016; 152 (7): 846-847

    View details for DOI 10.1001/jamadermatol.2016.0001

    View details for PubMedID 26964004

  • A fibrous papule with abundant CD34-immunoreactive ganglion-like multinucleated giant cells: a case report and review of the literature. Dermatology online journal Schaberg, K. B., Chiou, A. S., Wang, K. C., Egbert, B. M. 2015; 21 (7)

    Abstract

    Fibrous papules present clinically as benign, asymptomatic, dome-shaped, flesh colored papules on the face. Histologically, fibrous papules are characterized by fibrous stroma with fibroblasts and dilated blood vessels. Multiple variants of fibrous papules have been reported. Although scattered multinucleated cells in fibrous papules have been well described, we report a fibrous papule with abundant multinucleated ganglion-like giant cells that were immunoreactive with CD34. Recognition of such fibrous papule variants is important to avoid misdiagnosis as potentially more worrisome and/or aggressive melanocytic, soft tissue, or neural lesions that may require more aggressive treatment. Indeed, fibrous papules do not commonly appear on the differential diagnosis for lesions with multinucleated giant cells or ganglion-like cells and consideration should be given to their inclusion in the appropriate clinical setting.

    View details for PubMedID 26436978

  • Tazarotene: randomized, double-blind, vehicle-controlled, and open-label concurrent trials for Basal cell carcinoma prevention and therapy in patients with Basal cell nevus syndrome. Cancer prevention research Tang, J. Y., Chiou, A. S., Mackay-Wiggan, J. M., Aszterbaum, M., Chanana, A. M., Lee, W., Lindgren, J. A., Raphael, M. A., Thompson, B. J., Bickers, D. R., Epstein, E. H. 2014; 7 (3): 292-299

    Abstract

    Sporadic human basal cell carcinomas (BCC) are generally well managed with current surgical modalities. However, in the subset of high-risk patients predisposed to developing large numbers of BCCs, there is an unmet need for effective, low-morbidity chemoprevention. This population includes fair-skinned patients with extensive sun exposure and those with genodermatoses such as the basal cell nevus (Gorlin) syndrome (BCNS). Tazarotene (Tazorac, Allergan) is a topical retinoid with relative specificity for RAR-β and RAR-γ receptors. We previously demonstrated tazarotene's robust anti-BCC efficacy in Ptch1(+/-) mice, a murine equivalent of BCNS, and others have found it to have some efficacy against sporadic human BCCs. We report here results of a randomized, double-blind, vehicle-controlled study in patients with BCNS evaluating the efficacy of topically applied tazarotene for BCC chemoprevention (N = 34 subjects), along with an open-label trial evaluating tazarotene's efficacy for chemotherapy of BCC lesions (N = 36 subjects) for a maximum follow-up period of 3 years. We found that only 6% of patients had a chemopreventive response and that only 6% of treated BCC target lesions were clinically cured. Our studies provide no evidence for either chemopreventive or chemotherapeutic effect of tazarotene against BCCs in patients with BCNS.

    View details for DOI 10.1158/1940-6207.CAPR-13-0305

    View details for PubMedID 24441673

    View details for PubMedCentralID PMC4323274

  • Advanced aging skin and itch: addressing an unmet need DERMATOLOGIC THERAPY Garibyan, L., Chiou, A. S., Elmariah, S. B. 2013; 26 (2): 92-103

    Abstract

    Itch is the most common skin disorder in the elderly and frequently diminishes quality of life in this population. The high prevalence of pruritus in elderly patients is attributed in part to the decline in the normal physiology of the advanced aging skin, and reflects poor hydration, impaired skin barrier, and altered neural function, all ultimately contributing to inflammation and pruritus. As the elderly population continues to grow, practitioners need to be aware of how to evaluate and manage pruritus, recognizing the common conditions contributing to itch in elderly patients as well as the challenges of treatment in this group. Ultimately, management of pruritus will require an individually tailored approach that is guided by a patient's general health, severity of symptoms, and the potential adverse effects of itch therapies.

    View details for DOI 10.1111/dth.12029

    View details for Web of Science ID 000317130100003

    View details for PubMedID 23551366

    View details for PubMedCentralID PMC4051285

  • Tumor angiogenesis as a target for dietary cancer prevention. Journal of oncology Li, W. W., Li, V. W., Hutnik, M., Chiou, A. S. 2012; 2012: 879623-?

    Abstract

    Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome), cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention.

    View details for DOI 10.1155/2012/879623

    View details for PubMedID 21977033

    View details for PubMedCentralID PMC3184418

  • Probing Neuroserpin Polymerization and Interaction with Amyloid-beta Peptides Using Single Molecule Fluorescence BIOPHYSICAL JOURNAL Chiou, A., Haeggloef, P., Orte, A., Chen, A. Y., Dunne, P. D., Belorgey, D., Karlsson-Li, S., Lomas, D. A., Klenerman, D. 2009; 97 (8): 2306-2315

    Abstract

    Neuroserpin is a member of the serine proteinase inhibitor superfamily. It can undergo a conformational transition to form polymers that are associated with the dementia familial encephalopathy with neuroserpin inclusion bodies and the wild-type protein can inhibit the toxicity of amyloid-beta peptides in Alzheimer's disease. We have used a single molecule fluorescence method, two color coincidence detection, to determine the rate-limiting steps of the early stages of the polymerization of fluorophore-labeled neuroserpin and have assessed how this process is altered in the presence of A beta(1-40.) Our data show that neuroserpin polymerization proceeds first by the unimolecular formation of an active monomer, followed by competing processes of both polymerization and formation of a latent monomer from the activated species. These data are not in keeping with the recently proposed domain swap model of polymer formation in which the latent species and activated monomer are likely to be formed by competing pathways directly from the unactivated monomeric serpin. Moreover, the A beta(1-40) peptide forms a weak complex with neuroserpin (dissociation constant of 10 +/- 5 nM) that increases the amount of active monomer thereby increasing the rate of polymerization. The A beta(1-40) is displaced from the complex so that it acts as a catalyst and is not incorporated into neuroserpin polymers.

    View details for DOI 10.1016/j.bpj.2009.07.057

    View details for Web of Science ID 000270892000021

    View details for PubMedID 19843463

    View details for PubMedCentralID PMC2764104

  • Reaction of Cl with CD4 excited to the second C-D stretching overtone JOURNAL OF CHEMICAL PHYSICS Martin, M. R., Brown, D. J., Chiou, A. S., Zare, R. N. 2007; 126 (4)

    Abstract

    The effects of vibrational excitation on the Cl+CD(4) reaction are investigated by preparing three nearly isoenergetic vibrational states: mid R:3000 at 6279.66 cm(-1), |2100> at 6534.20 cm(-1), and |1110> at 6764.24 cm(-1), where |D(1)D(2)D(3)D(4)> identifies the number of vibrational quanta in each C-D oscillator. Vibrational excitation of the perdeuteromethane is via direct infrared pumping. The reaction is initiated by photolysis of molecular chlorine at 355 nm. The nascent methyl radical product distribution is measured by 2+1 resonance-enhanced multiphoton ionization at 330 nm. The resulting CD(3) state distributions reveal a preference to remove all energy available in the most excited C-D oscillator. Although the energetics are nearly identical, the authors observe strong mode specificity in which the CD(3) state distributions markedly differ between the three Cl-atom reactions. Reaction with CD(4) prepared in the |3000> mode leads to CD(3) products populated primarily in the ground state, reaction with CD(4) prepared in the |2100> mode leads primarily to CD(3) with one quantum of stretch excitation, and reaction with CD(4) prepared in the |1110> mode leads primarily to CD(3) with one quantum of C-D stretch excitation in two oscillators. There are some minor deviations from this behavior, most notably that the Cl atom is able to abstract more energy than is available in a single C-D oscillator, as in the case of |2100>, wherein a small population of ground-state CD(3) is observed. These exceptions likely result from the mixings between different second overtone stretch combination bands. They also measure isotropic and anisotropic time-of-flight profiles of CD(3) (nu(1)=1,2) products from the Cl+CD(4) |2100> reaction, providing speed distributions, spatial anisotropies, and differential cross sections that indicate that energy introduced as vibrational energy into the system essentially remains as such throughout the course of the reaction.

    View details for DOI 10.1063/1.2431368

    View details for PubMedID 17286478

  • PHYS 379-Effects of reagent vibrational excitation on the Cl+CD4 reaction Martin, M. R., Brown, D. J., Chiou, A. S., Zare, R. N. AMER CHEMICAL SOC. 2006
  • Reaction products with internal energy beyond the kinematic limit result from trajectories far from the minimum energy path: An example from H+HBr -> H-2+Br JOURNAL OF THE AMERICAN CHEMICAL SOCIETY Pomerantz, A. E., Camden, J. P., Chiou, A. S., Ausfelder, F., Chawla, N., Hase, W. L., Zare, R. N. 2005; 127 (47): 16368-16369

    Abstract

    The importance of reactive trajectories straying far from the minimum energy path is demonstrated for the bimolecular reaction H + HBr --> H2(v', j') + Br at 53 kcal/mol collision energy. Product quantum state distributions are measured and calculated using the quasi-classical trajectory technique, and the calculations indicate that highly internally excited H2 products result from indirect reactive trajectories with bent transition states. A general argument is made suggesting that reaction products with internal energy exceeding a kinematic constraint can, in general, be attributed to reactive collisions straying far from the minimum energy path.

    View details for DOI 10.1021/ja055440a

    View details for PubMedID 16305203