Albert Sean Chiou, MD, MBA

All Publications

• 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

• 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., Ko, J., Honari, G. 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

  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

• 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

• 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

  View details for DOI 10.1073/pnas.1803733115

  View details for Web of Science ID 000435585200035

• Localized bullous pemphigoid in a melanoma patient with dual exposure to PD-1 checkpoint inhibition and radiation therapy. JAAD case reports Hirotsu, K., Chiou, A. S., Chiang, A., Kim, J., Kwong, B. Y., Pugliese, S. 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

  View details for Web of Science ID 000207781609087

• 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