Janet V. Cross

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Primary Appointment

Associate Professor, Pathology

Education

  • BS, Recombinant Gene Technology, Medical Technology, State University of New York College at Fredonia
  • PhD, Molecular Biology and Microbiology, Case Western Reserve University

Research Disciplines

Cancer Biology, Experimental Pathology, Immunology, Molecular Biology

Research Interests

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.

Personal Statement

The central objective of my lab is to understand how the host immune response is reprogrammed by tumors to promote growth and metastasis. My entire career has focused on the study of mechanisms that contribute to tumor development. Early on, my work centered on the regulation of cell signaling pathways and the aberrations in these networks that promote cell growth, prevent cell death or otherwise contribute to cancer. In the course of these studies, I performed an unbiased proteomics screen to identify molecular targets that might explain the anti-cancer activities of a well-studied class of cancer preventive compounds. We expected to identify a kinase or a transcription factor that might mediate their protective properties by interfering with signaling responses within the tumor cell. Instead, we identified an inflammatory cytokine, the Macrophage Migration Inhibitory Factor (MIF), as the major target of these cancer agents, a discovery that has taken my lab in an exciting new direction.

Training

  • Biodefense & Infectious Diseases Short-Term Training to Increase Diversity in Biomedical Sciences

Selected Publications

2019

Gigliotti, J. C., Tin, A., Pourafshar, S., Cechova, S., Wang, Y. T., Sung, S. -S. J., . . . Le, T. H. (2020). GSTM1 Deletion Exaggerates Kidney Injury in Experimental Mouse Models and Confers the Protective Effect of Cruciferous Vegetables in Mice and Humans. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 31(1), 102-116. doi:10.1681/ASN.2019050449

Calderon-Garciduenas, L., Gonzalez-Maciel, A., Mukherjee, P. S., Reynoso-Robles, R., Perez-Guille, B., Gayosso-Chavez, C., . . . Maher, B. A. (2019). Combustion- and friction-derived magnetic air pollution nanoparticles in human hearts. ENVIRONMENTAL RESEARCH, 176. doi:10.1016/j.envres.2019.108567

2018

Balogh, K. N., Templeton, D. J., & Cross, J. V. (2018). Macrophage Migration Inhibitory Factor protects cancer cells from immunogenic cell death and impairs anti-tumor immune responses. PLOS ONE, 13(6). doi:10.1371/journal.pone.0197702

2017

Dill, E. A., Gru, A. A., Atkins, K. A., Friedman, L. A., Moore, M. E., Bullock, T. N., . . . Mills, A. M. (2017). PD-L1 Expression and Intratumoral Heterogeneity Across Breast Cancer Subtypes and Stages An Assessment of 245 Primary and 40 Metastatic Tumors. AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 41(3), 334-342. doi:10.1097/PAS.0000000000000780

Gottlieb, C. E., Mills, A. M., Cross, J. V., & Ring, K. L. (2017). Tumor-associated macrophage expression of PD-L1 in implants of high grade serous ovarian carcinoma: A comparison of matched primary and metastatic tumors. GYNECOLOGIC ONCOLOGY, 144(3), 607-612. doi:10.1016/j.ygyno.2016.12.021

Balogh, K. N., & Cross, J. V. (2017). A role for Macrophage Migration Inhibitory Factor (MIF) in breast cancer growth and metastasis. CANCER IMMUNOLOGY RESEARCH, 5(3). doi:10.1158/2326-6074.TUMIMM16-A03

Dill, E., Thompson, E., Gottlieb, C., Bullock, T., Cross, J., Atkins, K., . . . Mills, A. (2017). PD-L1 Expression and Intratumoral Heterogeneity Across Breast Cancer Subtypes: An Assessment of 245 Primary and 40 Metastatic Tumors. In MODERN PATHOLOGY Vol. 30 (pp. 39A). Retrieved from https://www.webofscience.com/

Dill, E., Thompson, E., Gottlieb, C., Bullock, T., Cross, J., Atkins, K., . . . Mills, A. (2017). PD-L1 Expression and Intratumoral Heterogeneity Across Breast Cancer Subtypes: An Assessment of 245 Primary and 40 Metastatic Tumors. In LABORATORY INVESTIGATION Vol. 97 (pp. 39A). Retrieved from https://www.webofscience.com/

2016

Damle, S. R., Martin, R. K., Cross, J. V., & Conrad, D. H. (2017). Macrophage migration inhibitory factor deficiency enhances immune response to Nippostrongylus brasiliensis. MUCOSAL IMMUNOLOGY, 10(1), 205-214. doi:10.1038/mi.2016.29

Balogh, K. N., & Cross, J. V. (2016). The macrophage migration inhibitory factor promotes breast cancer metastasis through interaction with the host immune response. In CANCER IMMUNOLOGY RESEARCH Vol. 4. doi:10.1158/2326-6074.CRICIMTEATIAACR15-A152