Janet V. Cross


  • BS, State University of New York College at Fredonia
  • PhD, Case Western Reserve University

Primary Appointment

  • Associate Professor, Pathology


Research Interest(s)

Contribution of the Inflammatory Microenvironment to Tumor Initiation, Progression and Metastasis; Molecular Mechanisms of Cancer Chemoprevention

Research Description

The central objective of my lab is to understand how the host immune response is reprogrammed by tumors to promote growth and metastasis. Specifically, we focus on the role of an inflammatory cytokine, the Macrophage Migration Inhibitory Factor (MIF) in cancer. We identified MIF as a target for inhibition by a class of cancer preventive agents present in fresh vegetables, including broccoli. MIF is overexpressed in many cancers, and the degree of overexpression correlates with tumor aggressiveness and metastatic potential. This observation supported our efforts to determine how MIF might contribute to cancer. In recently published work, we have established that MIF promotes tumor growth and is required for tumor metastasis. We demonstrated that MIF carries out its pro-tumor effects through influence over the host immune system, rather than by altering an intrinsic property of the tumor cells. Specifically we discovered that MIF regulates the abundance of a class of immunosuppressive cells within the tumor microenvironment. These cells, monocytic Myeloid Derived Suppressor Cells (Mo-MDSCs) suppress T cell mediated immune responses, thereby protecting the tumor from immune destruction. In this study, we demonstrated that treating tumor bearing mice with our MIF inhibitory compound reduces the abundance of Mo-MDSCs in the tumors, suggesting that we may be able to target MIF therapeutically to inhibit tumor progression through manipulation of the host immune response. The primary goal of ongoing work in our lab is to further understand the mechanisms by which MIF regulates the tumor microenvironment to promote tumor progression. Additionally, we continue to evaluate the potential utility of our inhibitor as a therapeutic approach in other MIF-dependent inflammatory disease processes.

Selected Publications

  • Dill E, Gru A, Atkins K, Friedman L, Moore M, Bullock T, Cross J, Dillon P, Mills A. PD-L1 Expression and Intratumoral Heterogeneity Across Breast Cancer Subtypes and Stages: An Assessment of 245 Primary and 40 Metastatic Tumors. The American journal of surgical pathology. 2017;41(3): 334-342. PMID: 28195880
  • Damle S, Martin R, Cross J, Conrad D. Macrophage migration inhibitory factor deficiency enhances immune response to Nippostrongylus brasiliensis. Mucosal immunology. 2016;10(1): 205-214. PMID: 27049059 | PMCID: PMC5053838
  • Conine S, Cross J. MIF deficiency does not alter glucose homeostasis or adipose tissue inflammatory cell infiltrates during diet-induced obesity. Obesity (Silver Spring, Md.). 2013;22(2): 418-25. PMID: 23804488 | PMCID: PMC3809343
  • Simpson K, Cross J. MIF: metastasis/MDSC-inducing factor? Oncoimmunology. 2013;2(3): e23337. PMID: 23802077 | PMCID: PMC3661162
  • Simpson K, Templeton D, Cross J. Macrophage migration inhibitory factor promotes tumor growth and metastasis by inducing myeloid-derived suppressor cells in the tumor microenvironment. Journal of immunology (Baltimore, Md. : 1950). 2012;189(12): 5533-40. PMID: 23125418 | PMCID: PMC3518629
  • Zhou J, Joplin D, Cross J, Templeton D. Sulforaphane inhibits prostaglandin E2 synthesis by suppressing microsomal prostaglandin E synthase 1. PloS one. 2012;7(11): e49744. PMID: 23166763 | PMCID: PMC3500324
  • Templeton D, Aye M, Rady J, Xu F, Cross J. Purification of reversibly oxidized proteins (PROP) reveals a redox switch controlling p38 MAP kinase activity. PloS one. 2010;5(11): e15012. PMID: 21085594 | PMCID: PMC2981573
  • Cross J, Rady J, Foss F, Lyons C, Macdonald T, Templeton D. Nutrient isothiocyanates covalently modify and inhibit the inflammatory cytokine macrophage migration inhibitory factor (MIF). The Biochemical journal. 2009;423(3): 315-21. PMID: 19723024 | PMCID: PMC2858637