My lab is interested in elucidating the molecular and cellular mechanisms involved in tumor-mediated immune suppression and cancer immunotherapy resistance. Our overriding hypothesis is that tumor cells and/or their associated stromal elements elicit soluble factors that tolerize local dendritic cell populations and/or recruit other immunosuppressive cell populations to the tumor bed; thereby, interfering with the generation of an effective anti-tumor immune response. This work has both basic and translational significance in that it is capable of providing 1. novel pharmacological targets for enhancing anti-tumor immunity and 2. much needed biomarkers for guiding the management of cancer patients with immunotherapies. We perform these investigations utilizing both transgenic murine models as well as clinical specimens derived from cancer patients undergoing immunotherapy. We focus these studies on melanoma, non-small cell lung cancer, pancreatic cancer, and colon cancer.
We currently have the following ongoing projects in our lab:
1. Investigating mechanisms by which developing cancers alter the metabolism of local dendritic cells thereby hijacking this antigen-presenting cell population to generate an immunotolerant tumor microenvironment.
2. Identifying soluble factors expressed by cancers which manipulate local dendritic cell function to drive regulatory T cell differentiation within the tumor microenvironment as well as any potential oncogenic signaling pathways driving this process.
3. Characterizing mechanisms of innate and adaptive resistance mechanisms to checkpoint inhibitor therapies.
4. Examining the role of the tumor stroma in interfering with immunotherapy efficacy.
5. Design and development of novel dendritic cell-based vaccine strategies
Education and Training
- Fellowship, Hematology/Oncology, Duke University School of Medicine, 2008 - 2012
- Internship and Residency, Internal Medicine, Duke University School of Medicine, 2006 - 2008
- M.D., Baylor College of Medicine, 2006
- Ph.D., Baylor College of Medicine, 2004
- Role of the tumor NLRP3 inflammasome in the generation of anti-PD-1 antibody immunotherapy-associated toxicities
- Exicure AST-008-102
- Exploration of Tumor-Intrinsic NLRP3 Signaling Regulators
- Targeting convergent oncogenic signaling during AR inhibition to overcome metastasis and immune evasion in prostate cancer
- Investigating the Role of a Novel Dendritic Cell Subset within Sentinel Lymph Node Tissues in Immune Evasion and Melanomagenesis
- Clinical Biomarker Study of the Tumor NLRP3 Inflammasome and its Role in Anti-PD-1 Immunotherapy Resistance
- Tumor-derived Exosome Induction of Dendritic Cell Tolerization
- Duke CTSA (TL1)
- Investigation of a Novel PD-L1:NLRP3 Inflammasome Activation Pathway as a Driver of Metastatic Recurrence
- Targeting the p38/Snail/PD-L1 axis in hormone-therapy resistance and metastasis
- Merck Sharp & Dohme Corp. Study Agreement
- Investigating the Role of EMT-mediated Dendritic Cell Tolerization in Checkpoint Inhibitor Resistance
- Investigating the Immunotherapeutic Properties of the DKK1 Antibody, DKN-01, in Pre-Clinical Models of Melanoma
- HSP70-TLR4-mediated MDSC Recruitment as an Adaptive Resistance
- Investigating the Impact of TPST-1120 PPAR ¿ Inhibition on Anti-PD-1 Antibody Immunotherapy Efficacy in Pre-Clinical Melanoma Models