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
- Baylor College of Medicine, Ph.D. 2004
- Baylor College of Medicine, M.D. 2006
- Duke University School of Medicine, Internship and Residency, Internal Medicine
- Duke University School of Medicine, Fellowship, Hematology/Oncology
Selected Grants and Awards
- Duke CTSA (KL2)
- Duke CTSA (TL1)
- Targeting the p38/Snail/PD-L1 axis in hormone-therapy resistance and metastasis
- Awakening the dormant tumor: the role of the tumor microenvironment in breast cancer recurrence
- Melanoma-mediated Dendritic Cell Tolerization and Immune Evasion
- Investigating the Impact of TPST-1120 PPAR ¿ Inhibition on Anti-PD-1 Antibody Immunotherapy Efficacy in Pre-Clinical Melanoma Models
- Merck Sharp & Dohme Corp. Study Agreement
- Investigating the Role of EMT-mediated Dendritic Cell Tolerization in Checkpoint Inhibitor Resistance
- Metabolic Reprogramming of Dendritic Cell-based Cancer Vaccines to Enhance Anti-Tumor Immunity
- Investigating the Combination PORCN Inhibitor, ETC-159, and Checkpoint Inhibitor Immunotherapy in Pre-Clinical Cancer Models
- CITN-09 A Phase II Study of MK-3475 in Patients with Advanced Merkel Cell Carcinoma (MCC)
- Investigation of the FZD8-Fc Wnt Ligand Antagonist and the Fzd Receptor Monoclonal Antibody in Combination with Immune Checkpoint Blockade in Pre-Clinical Melanoma, Non-Small Cell Lung Cancer, and Col
- Phase II Pilot Trial of an Indoleamine 2, 3,diosygenase -1 (IDO1) Inhibitor (INCBO24360) Plus a Multipeptide Melanoma Vaccine (MELTAC 12.1) in Patients with Advanced Melanoma (CITN-04)
- Investigating Oncogenic Signaling Pathways that Drive Wnt Ligand-mediated Immune Tolerance in Melanoma
- Seahorse XFe96 Extracellular Flux Analyzer
- A phase 1 / 2 randomized, blinded, placebo controlled study of Ipilimumab in combination with INCB024360 or placebo in u
- A Phase II, Open-label, Multicenter, Randomized Study of CDX-1401, a Dendritic Cell Targeting NY-ESO-1 Vaccine, in Patients with Malignant Melanoma Pre-Treated with Recombinant CDX-301, a Recombinant
- Phase II Pilot Trial of an Indoleamine 2, 3,diosygenase -1 ( IDO1) Inhibitor (INCBO24360) Plus a Multipeptide Melanoma Vaccine ( MELTAC 12.1 ) in Patients with Advanced Melanoma
- Therapeutic Targeting of the TGF-BSignaling Axis to Modulate the Tumor Immune Microenvironment and Enhance Melanoma Immu
- Investigation of TEW-7197 in Combination with Immune Checkpoint Inhibition in the BRAFV600E-PTEN-/- Melanoma Model
- A phase II pilot trial of an Indoleamine2,3, dioxygenase-1 (IDO1) Inhibitor (INCB024360) plus a multipeptide melanoma v
- A phase II, open-label, multicenter, randomized study of CDX-1401 a Dendritic Cell targeting NY-ESO-1 vaccine, in patien
- Role of Type III TGF-b Receptor in Mediating Immunosuppression During Breast Cancer Progression