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    Overview

    Research Areas (IRP Lab Groups)

    Cancer Biology,
    Computational Biology,
    Skin Biology

    The Cutaneous Development and Carcinogenesis Section studies the signaling pathways such as Hedgehog signaling that regulate the development and maintenance of normal skin and the changes in these signals that occur during the formation of skin cancer. Our investigations include studying the specification and maintenance of cell lineages in the skin, studying the regulation of stem cells in the skin, and using mouse genetics to model carcinogenesis in the skin.

    A current focus for our research is investigating the neuro-cutaneous interface and the regulation of neuroendocrine cells (Merkel cells) in the skin. We are also analyzing Merkel cell carcinomas and are developing pre-clinical mouse models for this uncommon but aggressive skin cancer.

    Ongoing Clinical Trials

    The following studies are currently active. Further details are available following the links to the respective pages on the clinicaltrials.gov web site.

    RECRUITING

    A Phase II, Open-Label, Multicenter Trial to Investigate the Clinical Activity and Safety of MSB0010718C in Subjects with Merkel Cell Carcinoma

    ClinicalTrials.gov Identifier: NCT02155647

    This is a multicenter, international, single-arm, open-label, Phase 2 trial to evaluate the efficacy and safety of avelumab in participants with metastatic Merkel cell carcinoma (MCC).

    Related NIAMS Labs

    Scientific Advances

    Understanding How Skin Cancer Presentation and Survival Differs by Racial and Ethnic Groups
    Clinical Practice Guidelines for Nonmelanoma Skin Cancer

    Core Research Facilities

    Labs at the NIAMS are supported by the following state-of-the-art facilities and services:

    Image & Media Gallery

    Brownell Lab group photo.
    Brownell Lab
    Brownell lab members posing in the hall.
    Brownell Lab Group Photo
    Cutaneous Development and Carcinogenesis Section group photo
    Cutaneous Development and Carcinogenesis Section group photo
    2 Scientists discuss over on the computer lab
    CDCS Lab
    2 scientists demonstration a machine
    Medical equipment demonstration

    Career Opportunities

    We are seeking outstanding, highly motivated postdoctoral fellows to join our lab. There are open positions investigating skin cancer and/or skin stem cells. We conduct basic and translational studies using mouse genetics, tissue culture, mouse xenografts, and patient samples. Multiomic high-throughput technologies are applied including FACS-seq, scRNA-seq, ChIP-seq, HiChIP, functional genomics screening, and small molecule screening. Experience with cancer biology, developmental biology, or stem cell biology preferred.

    General Requirements

    Applicants should have a Ph.D. or M.D. with relevant biomedical research experience; Peer-reviewed publications; Strong oral and written communication skills; Strong ability to work collaboratively and independently.

    Please send a cover letter with statement of research interests, a CV with a publication list, and the contact information of three references to Dr. Brownell (isaac.brownell@nih.gov).

    Scientific Publications

    Selected Recent Publications

    Mycophenolate mofetil inhibits Merkel cell carcinoma growth.

    Garman KA, Thoreson N, Strong J, Hallaert P, Gelb T, Shen M, Hall MD, Brownell I
    Br J Dermatol.
    2024 Mar 15;
    190(4).
    doi: 10.1093/bjd/ljae018
    PMID: 38266271

    Genetic Risk Factors for Early-Onset Merkel Cell Carcinoma.

    Mohsin N, Hunt D, Yan J, Jabbour AJ, Nghiem P, Choi J, Zhang Y, Freeman AF, Bergerson JRE, Dell'Orso S, Lachance K, Kulikauskas R, Collado L, Cao W, Lack J, Similuk M, Seifert BA, Ghosh R, Walkiewicz MA, Brownell I
    JAMA Dermatol.
    2024 Feb 1;
    160(2).
    doi: 10.1001/jamadermatol.2023.5362
    PMID: 38170500

    ATOH1, TFAP2B, and CEACAM6 as Immunohistochemical Markers to Distinguish Merkel Cell Carcinoma and Small Cell Lung Cancer.

    Vilasi SM, Nguyen J, Wang CJ, Miao L, Daily K, Eid M, Song JS, Jiang H, Ylaya K, Busam KJ, Gaiser MR, Hewitt SM, Brownell I
    Cancers (Basel).
    2024 Feb 15;
    16(4).
    doi: 10.3390/cancers16040788
    PMID: 38398178

    Mycophenolate mofetil inhibits Merkel cell carcinoma growth.

    Garman KA, Thoreson N, Strong J, Hallaert P, Gelb T, Shen M, Hall MD, Brownell I
    Br J Dermatol.
    2024 Mar 15;
    190(4).
    doi: 10.1093/bjd/ljae018
    PMID: 38266271

    Differences in Merkel Cell Carcinoma Presentation and Outcomes Among Racial and Ethnic Groups.

    Mohsin N, Martin MR, Reed DJ, Vilasi SM, Miao L, Hill NT, Brownell I
    JAMA Dermatol.
    2023 May 1;
    159(5).
    doi: 10.1001/jamadermatol.2023.0061
    PMID: 36920369

    Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of nonmelanoma skin cancer.

    Silk AW, Barker CA, Bhatia S, Bollin KB, Chandra S, Eroglu Z, Gastman BR, Kendra KL, Kluger H, Lipson EJ, Madden K, Miller DM, Nghiem P, Pavlick AC, Puzanov I, Rabinowits G, Ruiz ES, Sondak VK, Tavss EA, Tetzlaff MT, Brownell I
    J Immunother Cancer.
    2022 Jul;
    10(7).
    doi: 10.1136/jitc-2021-004434
    PMID: 35902131

    Distinct Signatures of Genomic Copy Number Variants Define Subgroups of Merkel Cell Carcinoma Tumors.

    Hill NT, Kim D, Busam KJ, Chu EY, Green C, Brownell I
    Cancers (Basel).
    2021 Mar 6;
    13(5).
    doi: 10.3390/cancers13051134
    PMID: 33800889

    Robust Production of Merkel Cell Polyomavirus Oncogene Specific T Cells From Healthy Donors for Adoptive Transfer.

    Davies SI, Barrett J, Wong S, Chang MJ, Muranski PJ, Brownell I
    Front Immunol.
    2020;
    11().
    doi: 10.3389/fimmu.2020.592721
    PMID: 33362774

    Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial.

    D'Angelo SP, Bhatia S, Brohl AS, Hamid O, Mehnert JM, Terheyden P, Shih KC, Brownell I, Lebbé C, Lewis KD, Linette GP, Milella M, Georges S, Shah P, Ellers-Lenz B, Bajars M, Güzel G, Nghiem PT
    J Immunother Cancer.
    2020 May;
    8(1).
    doi: 10.1136/jitc-2020-000674
    PMID: 32414862

    Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma.

    D'Angelo SP, Hunger M, Brohl AS, Nghiem P, Bhatia S, Hamid O, Mehnert JM, Terheyden P, Shih KC, Brownell I, Lebbé C, Lewis KD, Linette GP, Milella M, Schlichting M, Hennessy MH, Bharmal M
    Cancer Immunol Immunother.
    2019 Apr;
    68(4).
    doi: 10.1007/s00262-018-02295-4
    PMID: 30721341

    The biology and treatment of Merkel cell carcinoma: current understanding and research priorities.

    Harms PW, Harms KL, Moore PS, DeCaprio JA, Nghiem P, Wong MKK, Brownell I, International Workshop on Merkel Cell Carcinoma Research (IWMCC) Working Group
    Nat Rev Clin Oncol.
    2018 Dec;
    15(12).
    doi: 10.1038/s41571-018-0103-2
    PMID: 30287935

    Merkel cell carcinoma expresses the immunoregulatory ligand CD200 and induces immunosuppressive macrophages and regulatory T cells.

    Gaiser MR, Weis CA, Gaiser T, Jiang H, Buder-Bakhaya K, Herpel E, Warth A, Xiao Y, Miao L, Brownell I
    Oncoimmunology.
    2018;
    7(5).
    doi: 10.1080/2162402X.2018.1426517
    PMID: 29721394

    Melanoma in patients with GATA2 deficiency.

    Nguyen J, Alexander T, Jiang H, Hill N, Abdullaev Z, Pack SD, Hsu AP, Holland SM, Hickstein DD, Engels EA, Brownell I
    Pigment Cell Melanoma Res.
    2018 Mar;
    31(2).
    doi: 10.1111/pcmr.12671
    PMID: 29156497

    Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial.

    Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, Shih KC, Lebbé C, Linette GP, Milella M, Brownell I, Lewis KD, Lorch JH, Chin K, Mahnke L, von Heydebreck A, Cuillerot JM, Nghiem P
    Lancet Oncol.
    2016 Oct;
    17(10).
    doi: 10.1016/S1470-2045(16)30364-3
    PMID: 27592805

    A Cascade of Wnt, Eda, and Shh Signaling Is Essential for Touch Dome Merkel Cell Development.

    Xiao Y, Thoresen DT, Miao L, Williams JS, Wang C, Atit RP, Wong SY, Brownell I
    PLoS Genet.
    2016 Jul;
    12(7).
    doi: 10.1371/journal.pgen.1006150
    PMID: 27414798

    Evaluating blood levels of neuron specific enolase, chromogranin A, and circulating tumor cells as Merkel cell carcinoma biomarkers.

    Gaiser MR, Daily K, Hoffmann J, Brune M, Enk A, Brownell I
    Oncotarget.
    2015 Sep 22;
    6(28).
    doi: 10.18632/oncotarget.4500
    PMID: 26299616

    Neural Hedgehog signaling maintains stem cell renewal in the sensory touch dome epithelium.

    Xiao Y, Thoresen DT, Williams JS, Wang C, Perna J, Petrova R, Brownell I
    Proc Natl Acad Sci U S A.
    2015 Jun 9;
    112(23).
    doi: 10.1073/pnas.1504177112
    PMID: 26015562

    News & Highlights

    Scanning electron micrograph of S. aureus bacteria escaping destruction by human white blood cells.
    Spotlight on Research |

    NIH Researchers Survey the Genetic Diversity of Skin Microbes in Eczema Patients

    Using a combination of sequencing techniques, researchers from NIAMS and the National Human Genome Research Institute (NHGRI) surveyed the skin microbiome of patients with atopic dermatitis (AD, also called eczema) to understand the genetic diversity of the bacteria present on the skin and how genetic variants may contribute to disease severity.
    Read More
    Healthy human skin cells (yellow) are home to bacteria (bright pink), fungi (light blue), and other microorganisms.
    NIH Director's Blog |

    NIH Director's Blog

    Human skin is home to diverse ecosystems including bacteria, viruses, and fungi. These microbial communities comprise hundreds of species and are collectively known as the skin microbiome.
    Read More
    Photo of Drs. Kong and Myles
    NIAMS-Related Article |

    Drs. Heidi Kong and Ian Myles — Derm Germs: The Human Skin Microbiome

    Dr. Heidi Kong uses genomics to uncover the microbe-host interactions taking place all over our skin.
    Read More
    Portraits of Drs. Isaac Brownell, Heidi Kong, and Chris Nagao
    |

    NIAMS Investigators Elected to the American Society for Clinical Investigation

    Congratulations to Drs. Isaac Brownell, Heidi Kong, and Chris Nagao who were elected to the American Society for Clinical Investigation!
    Read More
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    Last Updated: April 2024
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