March 27, 2019

Brian Koss

Ph.D. Candidate
UAMS College of Medicine
Graduate Program in Interdisciplinary Biomedical Sciences
Track: Biochemistry and Molecular Biology
Mentor: Alan Tackett, Ph.D.

Research Interest Statement

  • Apoptosis in cancer and the immune system
  • Development and regulation of the immune system
  • Metabolic control of T cell fate and function

My research focuses on identifying new approaches to combat the metabolic suppression of an immune response in solid tumors. More specifically, I aim to mechanistically define epigenetically controlled metabolic stress responses in T cells during tumor infiltration. We have identified an epigenetic mechanism in which T cells are sensitized and made vulnerable to metabolic stress. Our preliminary work shows that the histone modifying enzyme EZH2 is targeted during melanoma infiltration and that this inhibition leads to the metabolic exhaustion of tumor infiltrating T cells. The identification of these mechanisms and demonstration of proof of principle therapies will set the stage for the next generation of immunotherapies.

Cancer-related Funding

NCI- F31CA232464

Epigenetic regulation of metabolic stress pathways in melanoma infiltrating lymphocytes

Principle Investigator

$36,868*

3/2019-3/2022

*cancer-related annual direct costs

UAMS Collaborators

Alan Tackett, Ph.D. (Biochemistry and Molecular Biology)

Stephanie Byrum, Ph.D. (Bioinformatics Core)

Martin Cannon, Ph.D. (Microbiology and Immunology)

Nukhet Aykin-Burns, Ph.D. (Pharmaceutical Sciences)

Timothy Chambers, Ph.D. (Biochemistry and Molecular Biology)

Charles O’Brien, Ph.D. (Orthopaedic Surgery)

External Collaborators

Joseph Opferman Ph.D. (St. Jude Children’s Research Hospital)

Sean Taverna Ph.D. (Johns Hopkins)

G. Greg Wang (UNC Lineberger)

Opportunities for Collaboration

I am always interested in having scientific conversations on the topics of immunology, metabolism and cancer biology.

You Might Not Know That …

My wife, Cary, and I have two boys, Bennett (4 years) and Parker (2 years).

Cancer-related Publications

See a complete list of publications here.

Shields BD, Koss B, Storey AJ, Taylor EM, et al. E-cadherin loss enables melanoma checkpoint blockade resistance by escape from CD103 immune responses. Cancer Research. 1722.2018

Shields BD, Mahmoud F, Taylor EM, Byrum SD, Sengupta D, Koss B, et al. Indicators of responsiveness to immune checkpoint inhibitors. Scientific Reports. 2017;7:807.

Koss B, Ryan J, Budhraja A, et al. Defining specificity and on-target activity of BH3-mimetics using engineered B-ALL cell lines. Oncotarget. 2016;7(10):11500-11511.

Koss B, Morrison J, Perciavalle RM, et al. Requirement for antiapoptotic MCL-1 in the survival of BCR-ABL B-lineage acute lymphoblastic leukemia. Blood. 2013;122(9):1587-1598.

Tripathi P, Koss B, Opferman JT, Hildeman DA. Mcl-1 antagonizes Bax/Bak to promote effector CD4+ and CD8+ T-cell responses. Cell Death and Diff. 2013;20(8):998-1007.