The Mohawk (mkx) gene functions as a transcriptional repressor for tendon morphogenesis during embryonic development. Previous research showed that mkx KO mice overexpressed the osteogenic gene Runx2. Runx2 plays a role in recognition and long-term immune memory. A study showed Runx2 KO mice had a significantly lower number of CD8 T cells specific to lymphocytic choriomeningitis virus (LCMV) and CD8 memory precursor T cells. To determine the direct effects of Mohawk expression on the immune system, development, acute response, and immune memory of innate, B and T cells were compared between WT and mkx KO mice after LCMV infection. Paired t-test analyses were performed between KO and WT data. We first found significantly higher numbers of granulocytes and dendritic cells in the periphery but lower numbers of B cells in the bone marrow and T cells in the thymus of KO mice. When analyzing immune response, we observed a significantly high number of activated CD8 T cells that proliferated in the KO mice in response to the infection. Next, we found no difference in cytokine production for TNF and IFNγ which shows Mohawk does not impair acute immune response. Finally, we found no significant difference between WT and KO mice in the CD8 T cells' ability to make an immune memory. In the present study, we found that, fewer immune cells continued their maturation. However, Mohawk expression did not impact their acute response or ability to become memory cells once the T cells matured and became activated. Rather, T cells specific for LCMV were present in higher numbers in mkx KO mice. Further research will study the impact Mohawk has on both B and T cell memory.

Adaptive therapy utilizes competitive interactions between resistant and sensitive cells by keeping some sensitive cells to control tumor burden with the aim of increasing overall survival and time to progression. The use of adaptive therapy to treat breast cancer, ovarian cancer, and pancreatic cancer in preclinical models has shown significant results in controlling tumor growth. The purpose of this thesis is to draft a protocol to study adaptive therapy in a preclinical model of breast cancer on MCF7, estrogen receptor-positive, cells that have evolved resistance to fulvestrant and palbociclib (MCF7 R). In this study, we used two protocols: drug dose adjustment and intermittent therapy. The MCF7 R cell lines were injected into the mammary fat pads of 11-month-old NOD/SCID gamma (NSG) mice (18 mice) which were then treated with gemcitabine.<br/>The results of this experiment did not provide complete information because of the short-term treatments. In addition, we saw an increase in the tumor size of a few of the treated mice, which could be due to the metabolism of the drug at that age, or because of the difference in injection times. Therefore, these adaptive therapy protocols on hormone-refractory breast cancer cell lines will be repeated on young, 6-week old mice by injecting the cell lines at the same time for all mice, which helps the results to be more consistent and accurate.