Dr. Mitchell’s laboratory work is primarily concentrated on characterizing the functional and mechanistic contributions of macrophage migration inhibitory factor (MIF) family member-dependent tumor progression. One active project involves the study of MIF and it’s only known family member, D-dopachrome tautomerase (D-DT) as they synergistically promote the growth and survival of human non-small cell lung carcinoma focusing on the AMPK and p53 tumor suppressor pathways (Brock et al. Negative regulation of AMPK activity by MIF family members in NSCLC. J. Biol. Chem. 287(45):37917-25; Brock et al. MIF Family Members Cooperatively Inhibit p53 Expression and Activity. PLoS One 16;9(6):e99795). Another very active area of investigation in the lab is the study of MIF and D-DT in a variety of tumor-stromal cell populations. For example, we recently identified an important role for monocyte/macrophage-derived MIF in promoting melanoma disease progression in mice (Yaddanapudi et al. Control of tumor-associated macrophage alternative activation by macrophage migration inhibitory factor. J Immunol. 190(6):2984-93.) and are currently evaluating the functional importance of MIF in circulating myeloid-derived suppressor cells to human malignant melanoma disease progression. Our laboratory is currently utilizing whole body MIF-deficient, D-DT-deficient and conditional MIF:D-DT-double deficient mice as well as monocyte specific MIF:D-DT-conditionally deficient mouse models to stringently evaluate the endogenous contributions of both MIF family members to monocytic stromal cell-dependent tumor progression. Finally, a significant portion of our lab’s efforts are devoted to identifying novel - and optimizing existing - small molecule therapeutics specifically targeting MIF (Winner et al. A novel, macrophage migration inhibitory factor suicide substrate inhibits motility and growth of lung cancer cells. Cancer Res. 68(18):7253-7.), D-DT or both. Given the importance of MIF family members to both tumor cell-dependent and stromal dependent pro-tumorigenic processes, the translational potential of these small molecule therapeutics is potentially very high.