Paracrine Wnt5a-β-Catenin Signaling Triggers a Metabolic Program that Drives Dendritic Cell Tolerization.

I am an Assistant Professor of Medical Oncology who primarily treats patients with colon cancer and gastroesophageal cancers. My laboratory and translational research is focused on tumor immune evasion and immunotherapy, particularly in the setting of metastasis. This work has led to a specific interest in tumor-mediated development of dendritic cell tolerance and suppressive myeloid populations. The ultimate goal of this research is to create biomarker-directed immunotherapies for advanced gastrointestinal cancers.

I have 22 years of experience in the field of cancer vaccines and immunotherapy and I am an accomplished T cell immunologist. Laboratory website:
https://surgery.duke.edu/immunology-inflammation-immunotherapy-laboratory

Current projects in the Nair Laboratory:
1] Dendritic cell vaccines using tumor-antigen encoding RNA (mRNA, total tumor RNA, amplified tumor mRNA)
2] Local immune receptor modulation using mRNA that encodes for antibodies, receptor-ligands, cytokines, chemokines and toll-like receptors (current target list: CTLA4, GITR, PD1, TIM3, LAG3, OX40 and 41BB)
3] Combination therapies for cancer: cytotoxic therapy (radiation, chemo and oncolytic poliovirus therapy) with dendritic cell-based vaccines and immune checkpoint blockade
4] Adoptive T cell therapy using tumor RNA-transfected dendritic cells to expand tumor-specific T cells ex vivo
5] Adoptive T cell therapy using PSMA CAR (chimeric antigen receptor) RNA-transfected T cells
6] Direct injection of tumor antigen encoding RNA (targeting antigens to dendric cells in vivo using nanoparticles and aptamers)

We are interested in understanding the mechanisms that cancers have evolved to suppress the generation of tumor antigen-specific immune responses and how this knowledge can be exploited for the development of novel and more effective cancer immunotherapy strategies. This work involves the utilization of both autochthonous transgenic tumor model systems as well as clinical specimens to develop novel strategies to enhance the efficacy of immunotherapies while also developing predictive biomarkers to better guide the management of cancer patients with these agents. We strive to translate our understanding of the fundamental biochemical and metabolic pathways within the tumor microenvironment that are critical for driving immune evasion and resistance into early phase clinical trial testing.

Our work utilizes a variety of techniques and methodologies that span the breadth of basic biological research. This work integrates studies based on both 1) transgenic mouse tumor models that are monitored using bioluminescence and micro-CT imaging and 2) a variety of clinical specimens.

Our current areas of focus include:

1. Investigating mechanisms of adaptive or acquired immunotherapy resistance in cancer
2. Studying the relationship between EMT pathways and immunotherapy resistance.
3. Elucidating mechanisms of dendritic cell tolerization in the tumor microenvironment and how these processes may contribute to immunotherapy resistance
4. Development of novel pharmacologic and genetic strategies to overcome immunotherapy resistance
5. Investigating mechanisms contributing to select immunotherapy-associated toxicities