PROJECT 2 NITRIC OXIDE IN THE TUMOR MICROENVIRONMENT OF TRIPLE NEGATIVE BREAST CANCER We propose to uncover how tumor produced nitric oxide drives tumor aggressiveness and immune evasion in triple negative breast cancer (TNBC). We also seek to increase research opportunities in cancer biology for Native American students. TNBC is an aggressive and metastatic form of breast cancer for which there are no targeted therapies. TNBC disproportionately affects Native American women and leads to worse outcomes than for non-Hispanic White women. Overall, Native American women have a 30-70% higher risk of dying from breast cancer when compared to other ethnicities. Our long-term goals are to develop much-needed new therapies for TNBC and to increase the pool of Native Americans with a focus on cancer research. Our team brings together Dr. Narendiran Rajasekaran, an Assistant Professor at Northern Arizona University (NAU) with a strong background in cancer biology and innate immunity, and Dr. William Montfort, a University of Arizona Cancer Center Professor with strength in structural biology, therapeutic development and nitric oxide signaling. Our project meshes with the Partnership for Native American Cancer Prevention (NACP) through our focus on a form of cancer of high importance to the Native American community, and through our efforts to train emerging Native American scientists in cancer biology. Our preliminary data uncover a link between tumor-derived nitric oxide and enhanced hypoxic signaling, which leads to a gene expression profile favoring tumor promotion, including growth, glycolysis, migration and immune cell evasion. We have three aims.
Aim 1 is to uncover how nitric oxide induces tumor progression, using three breast cancer cell lines for in vitro work and the 4T1 allograft murine model for in vivo work.
Aim 2 is to uncover how nitric oxide induces tumor evasion of innate immunity through checkpoint blockade involving CD47 and PD-L1, and cytokine production. Focus is on both macrophages and natural killer cells and will make use of both xenograft and allograft breast cancer models.
Aim 3 is to recruit and train Native American students in cancer biology and increase the opportunities for cancer research at NAU. Native American students will be recruited into both laboratories. A particular focus will be on ensuring Prof. Rajasekaran successfully establishes his new laboratory at NAU with solid student training, funding and publications.
| Gilbert, Jack A; Blaser, Martin J; Caporaso, J Gregory et al. (2018) Current understanding of the human microbiome. Nat Med 24:392-400 |
| Bokulich, Nicholas A; Dillon, Matthew R; Zhang, Yilong et al. (2018) q2-longitudinal: Longitudinal and Paired-Sample Analyses of Microbiome Data. mSystems 3: |
| Varadaraj, Archana; Magdaleno, Carina; Mythreye, Karthikeyan (2018) Deoxycholate Fractionation of Fibronectin (FN) and Biotinylation Assay to Measure Recycled FN Fibrils in Epithelial Cells. Bio Protoc 8: |
| Bea, Jennifer W; de Heer, Hendrik Dirk; Valdez, Luis et al. (2018) Physical Activity among Navajo Cancer Survivors: A Qualitative Study. Am Indian Alsk Native Ment Health Res 25:54-73 |
| Bokulich, Nicholas A; Kaehler, Benjamin D; Rideout, Jai Ram et al. (2018) Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2's q2-feature-classifier plugin. Microbiome 6:90 |
| Huenneke, Laura F; Stearns, Diane M; Martinez, Jesse D et al. (2017) Key Strategies for Building Research Capacity of University Faculty Members. Innov High Educ 42:421-435 |
| Jim, Venessa; LaViolette, Corinne; Briehl, Margaret M et al. (2017) Spatial distribution of uranium in mice kidneys detected by laser ablation inductively coupled plasma mass spectrometry. J Appl Bioanal 3:43-48 |
| Schwartz, Anna L; de Heer, Hendrik Dirk; Bea, Jennifer W (2017) Initiating Exercise Interventions to Promote Wellness in Cancer Patients and Survivors. Oncology (Williston Park) 31:711-7 |
| Bokulich, Nicholas A; Rideout, Jai Ram; Mercurio, William G et al. (2016) mockrobiota: a Public Resource for Microbiome Bioinformatics Benchmarking. mSystems 1: |
| Corlin, Laura; Rock, Tommy; Cordova, Jamie et al. (2016) Health Effects and Environmental Justice Concerns of Exposure to Uranium in Drinking Water. Curr Environ Health Rep 3:434-442 |
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