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## Overview

#### Senior Investigator

Isaac Brownell, M.D., Ph.D.

isaac.brownell@nih.gov

#### 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.

### 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

                                  - Cutaneous Leukocyte Biology Section
                                  - Cutaneous Microbiome and Inflammation Section
                                  - Dermatology Consultation Service

#### Scientific Advances

May 1, 2023

Understanding How Skin Cancer Presentation and Survival Differs by Racial and Ethnic Groups

July 1, 2022

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:
                                        - Biodata Mining and Discovery
                                        - Flow Cytometry
                                        - Genomic Technology
                                        - Laboratory Animal Care and Use
                                        - Light Imaging
                                        - Translational Immunology

## Staff

**Isaac Brownell, M.D., Ph.D.**

isaac.brownell@nih.gov

**Amy Coxon, Ph.D.**

coxona@mail.nih.gov

**Khalid Garman, Ph.D.**

khalid.garman@nih.gov

**Patrick Hallaert, B.S.**

patrick.hallaert@nih.gov

**Natasha T. Hill, Ph.D.**

natasha.hill@nih.gov

**Jordan Jarvis, B.S.**

jordan.jarvis@nih.gov

**Jasmine Meltzer, B.A.**

jasmine.meltzer@nih.gov

**Lingling Miao, Ph.D.**

lingling.miao@nih.gov

**Jennifer Strong, B.S.**

jennifer.strong@nih.gov

## Image & Media Gallery

##### Brownell Lab

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##### Brownell Lab Group Photo

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##### Cutaneous Development and Carcinogenesis Section group photo

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Download High Res(14.1 MB)

##### CDCS Lab

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Download High Res(12.55 MB)

##### Medical equipment demonstration

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Download High Res(10.88 MB)

## 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.        

190(4).

###             Genetic Risk Factors for Early-Onset Merkel Cell Carcinoma.        

160(2).

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

16(4).

###             Mycophenolate mofetil inhibits Merkel cell carcinoma growth.        

190(4).

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

159(5).

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

10(7).

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

13(5).

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

11().

###             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.        

8(1).

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

68(4).

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

15(12).

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

7(5).

###             Melanoma in patients with GATA2 deficiency.        

31(2).

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

17(10).

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

12(7).

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

6(28).

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

112(23).

## News & Highlights

Spotlight on Research | May 25, 2023

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

Read More

NIH Director's Blog | March 24, 2022

### NIH Director's Blog

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NIAMS-Related Article | October 22, 2020

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

Read More

 | April 5, 2019

### NIAMS Investigators Elected to the American Society for Clinical Investigation

Read More

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