Overview

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).

Image & Media Gallery

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 Jan 24;
pii: ljae018. 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

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.
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.
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.
|

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!