Laboratory

Research

Overview

Dr. Gastman and lab members.

The Gastman Lab is focused on building the bridge between basic science and clinical practice in order to provide state of the art care for patients. Robust collaborative interactions between scientists, industry, and healthcare professionals allow the continued research into identifying disease states, diagnostic tools for detecting at-risk individuals, and the investigation of the efficacy of therapeutic interventions. 

Tumor Immunology and Immunotherapy Research:
We are interested in elucidating the tumor immunology and microenvironment leading to disease development and treatment response. Currently we are investigating the mechanisms by which a novel CD8+ T cell population discovered by our team mediates immunotherapy resistance, and are testing various therapy regimens targeting this T cell subset to improve responses to anti-PD-1 based therapy.

Preclinical Mouse Model Development:
The development of predictive preclinical models to evaluate ‘next-generation’ immunotherapies prior to clinical investigation in patients is a critical aspect of the work done at the Gastman Lab. We developed an all autologous humanized melanoma xenograft mouse model utilizing matched patient tumor cells and peripheral blood mononuclear cells to evaluate novel immunotherapies and synergistic combination treatment strategies.

Involvement of Cellular Death Responses and Pathways in Understanding Diseases: 
Biological events and pathways of cell death/aging mediate disease progressions and treatments, and often promote or inhibit therapeutic responses. We are interested in understanding one important molecule, MCL1, involved in these pathways. Our work highly entails the identification of putative small molecule inhibitors of these pathways, and analyzing their overall utility and effectiveness for therapeutic purposes. We recently found that specific DNA damaging chemotherapies promote nuclear MCL1 translocation in colorectal cancer (CRC) models. In p53null CRC, this process is associated with resistance to chemotherapeutic agents, the mechanism of which is distinct from the classical mitochondrial protection. 

Powering Research Through Industries:
Most of our work is a product of rich collaborations with industries focused in improving treatment regimens and overall patient care. In this space, we conduct immunotherapy testing, tumor infiltrative lymphocyte (TIL) therapy, tumor processing for molecular diagnosis, and are constantly looking for innovative approaches to improve the diagnosis and treatment of various malignancies. We have collaborated with industries in all stages of disease, from prevention and diagnostics to therapeutics and surgical innovation, to generate new advances in the field of medical oncology.  

In the News

Articles
Q&A: Identifying, treating rare mucosal melanoma | Healio

Katie's face: Where a bullet and an overdose intersected, Cleveland Clinic doctors gave new life | Cleveland.com

Face Transplants: The Changing Face of Medicine | Cleveland Clinic Newsroom

Historic face transplant gives suicide survivor a ‘second chance’ | CNN Health

Podcasts
Merkel Cell Carcinoma | Cancer Advances Podcast

Conversations in Mohs Surgery: Dr. Brian Gastman | ACMS Podcast

What to Know About Melanoma | Butts & Guts Podcast

Are face transplants the future of cosmetic surgery? | UK Podcasts – Eureka!

Translational Research in the Gastman Lab

Created with BioRender.com.

All numbers correlate to those at various steps of the workflow diagram.

1. Collection of tumor and blood samples from patients in surgery. Patients are mainly from high-risk melanoma and skin cancer programs. 
2. Processing of specimens in lab to collect tumor and immune cells, as well as frozen tumor and plasma.
3. Tumor and immune cells are injected to preclinical specimen to construct a humanized model, which mimics the patient’s unique cells and condition. Different therapies are tested on the specimens.
4. Blood, tumor and spleen are extracted from the preclinical specimen and analyzed through correlative studies, along with an analysis of biological events and pathways involved in cellular death responses and disease progression. 
5. Manuscripts are written based on conclusions from data collected during research and are subsequently published in various journals. 
   1. From here, the findings generated in this translational process can lead to the development of industry collaborations, the awarding of various grants (DOD, RO1, etc.), and the beginning of clinical trials for new patients.

Selected Publications

View publications for ,
(Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)

Publications

Li, C., Phoon, Y. P., Karlinsey, K., Tian, Y. F., Thapaliya, S., Thongkum, A., ... & Gastman, B. R. (2021). A high OXPHOS CD8 T cell subset is predictive of immunotherapy resistance in melanoma patients. Journal of Experimental Medicine, 219(1), e20202084.

Pfannenstiel, L. W., Diaz-Montero, C. M., Tian, Y. F., Scharpf, J., Ko, J. S., & Gastman, B. R. (2019). Immune-checkpoint blockade opposes CD8+ T-cell suppression in human and murine Cancer. Cancer immunology research, 7(3), 510-525.

Gastman, B. R., Zager, J. S., Messina, J. L., Cook, R. W., Covington, K. R., Middlebrook, B., ... & Vetto, J. T. (2019). Performance of a 31‐gene expression profile test in cutaneous melanomas of the head and neck. Head & Neck, 41(4), 871-879.

Bolesta, E., Pfannenstiel, L. W., Demelash, A., Lesniewski, M. L., Tobin, M., Schlanger, S. E., ... & Gastman, B. R. (2012). Inhibition of Mcl-1 promotes senescence in cancer cells: implications for preventing tumor growth and chemotherapy resistance. Molecular and cellular biology, 32(10), 1879-1892.

Presentations

Alkermes to Present Data on Nemvaleukin Alfa at the Society for Immunotherapy of Cancer's (SITC) 36th Annual Meeting. Presenter: Brian Gastman, MD

Nuclear translocation of McI-1 induces chemoresistance of colorectal cancer. Case Comprehensive Cancer Center Case Gastrointestinal Cancers SPORE Retreat. Virtual. May 19, 2021. Presenter: Brian Gastman, MD

Brian R. Gastman, Howard L. Kaufman. The Surgeon’s Impact on Tumor Immunotherapy. Surgery Committee Session Co-Chair. Society for Immunotherapy of Cancer's (SITC) 35th Anniversary Annual Meeting. 2020. November 11, 2020.

Lillian Sun, Jennifer Ko, Allison Vidimos, Shlomo Koyfman, Brian Gastman. A Distinctive Lineage Negative Cell Population Produces IL-17A in Cutaneous Squamous Cell Carcinoma.  Society for Immunotherapy of Cancer's (SITC) 34th Annual Meeting. 2019. November 6-10, 2019.

Brian R. Gastman. Metabolically active dysfunctional T cells are major regulators in immunotherapy response in melanoma.  The Korea Association of Immunologists national meeting. Seoul, Korea. September 6th, 2019.

Brian R. Gastman, Jeffery Koslow, Anthony Tufaro. Melanoma update course.  American Society of Plastic Surgeons Annual Meeting.  San Diego, CA.  September 2019.