Summary

Isaac Brownell, M.D., Ph.D., is a board-certified dermatologist and a fellow of the American Academy of Dermatology. He directs a research program that includes basic, translational, and clinical investigations of skin homeostasis and skin cancer. Dr. Brownell is an attending physician on the NIH Clinical Center’s Dermatology Consultation Service and he co-directs the Cutaneous Oncology Program at the Murtha Cancer Center, Walter Reed National Military Medical Center. He is also an Adjunct Investigator at the National Cancer Institute (NCI).

Research Statement

Dr. Brownell studies the regulation of cutaneous stem cells and the molecular pathogenesis of skin cancer. A current research focus is the biology of neuroendocrine Merkel cells and the oncogenesis of Merkel cell carcinoma. Using mouse genetics, he investigates the signals that regulate skin stem cell development and maintenance. Mouse models are also used to study targets identified by high-throughput oncogenomic analysis of human skin tumors. In complementary studies, high-throughput screening techniques are used to identify novel therapeutic targets and treatments for skin cancers. In collaboration with oncologists in the National Cancer Institute, Dr. Brownell conducts early phase clinical trials treating skin cancer.

Scientific Publications

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

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

Education

Baylor College of Medicine, Houston, TX
M.D./Ph.D.

University of Maryland, College Park
B.S., Electrical Engineering and Mathematics

Experience

After graduating from the Medical Scientist Training Program at Baylor College of Medicine, Dr. Brownell completed an internship at Christus St. Joseph Hospital in Houston, TX, and a Dermatology residency at the New York University School of Medicine. He completed a postdoctoral research fellowship on Hedgehog signaling and cutaneous stem cells in the lab of Dr. Alexandra Joyner at Memorial Sloan-Kettering Cancer Center where he was also a clinical faculty member on the Dermatology Service. His clinical practice focused on patients with high-risk skin cancers.

In 2011, Dr. Brownell joined the Dermatology Branch in the Center for Cancer Research, National Cancer Institute. In 2017, he and the Dermatology Branch transferred to the National Institute of Arthritis and Musculoskeletal and Skin Diseases where he is currently a Senior Investigator and Head of the Cutaneous Development and Carcinogenesis Section. Dr. Brownell is also an Adjunct Assistant Professor of Dermatology in the School of Medicine, Uniformed Services University of the Health Sciences, and he co-directs the Cutaneous Oncology Program, Murtha Cancer Center, Walter Reed National Military Medical Center.

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