Janet V. Cross
- AAS, Jefferson Community College
- BS, State University of New York College at Fredonia
- PhD, Case Western Reserve University
- PhD, Case Western Reserve University
- Assistant Professor, Pathology
- Phone: 434-243-9402
- Email: jvc5b@Virginia.EDU
Contribution of the Inflammatory Microenvironment to Tumor Initiation, Progression and Metastasis; Molecular Mechanisms of Cancer Chemoprevention; Anti-Inflammatory Benefits of Dietary Nutrient Compounds
Fresh fruits and vegetables are indisputable components of a healthy diet. However, mechanistic understandings of how food products impact human physiology are few. In addition to essential vitamins and minerals, many vegetables contain chemical compounds that have positive health effects. Among these is the isothiocyanate class of chemicals present in cruciferous vegetables such as broccoli. Isothiocyanates have been well characterized for their activity in preventing tumor development in carcinogen-challenged animals. However, little is know about how these compounds prevent cancer , and whether they may have other beneficial health effects.
The bioactive nutrient isothiocyanates (ITCs) are chemically reactive compounds whose structure suggests that they could covalently modify potential protein targets. Using a novel proteomics screen, we identified a prevalent protein target of ITC modification in the cell. This protein is implicated in the pathogenesis of a number of inflammatory diseases including rheumatoid arthritis, inflammatory bowel disease and asthma where studies have shown that it is a critical participant in the disease process. As a participant in signal transduction, gene expression, apoptosis and proliferation of target cells, this protein is a provocative molecular target for the isothiocyanates that could explain their chemopreventive activity. In addition, the central role of this protein in inflammatory disease processes may indicate a potential anti-inflammatory benefit for these nutrient compounds.
Using two of the most prevalent isothiocyanates in broccoli , sulforaphane and PEITC, we are working to characterize the importance of this protein target in the phenomenon of cancer chemoprevention. In addition, we are using both in vitro studies and animal models to characterize the potential of these compounds to interfere with inflammatory processes in an intact organism. These studies may define a molecular mechanism for action of cancer chemopreventives and allow the development of alternative approaches for cancer prevention. Moreoever, they may provide additional insights into the well-appreciated epidemiological link between inflammation and cancer risk and define a pharmacological target for intervention in these processes.
- Cross J, Templeton D. Regulation of signal transduction through protein cysteine oxidation. Antioxidants & redox signaling. 2006;8(9): 1819-27. PMID: 16987034
- Cross J, Foss F, Rady J, Macdonald T, Templeton D. The isothiocyanate class of bioactive nutrients covalently inhibit the MEKK1 protein kinase. BMC cancer. 2007;7 183. PMID: 17894894 | PMCID: PMC2071920
- 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
- Bhattacharyya A, Chattopadhyay R, Burnette B, Cross J, Mitra S, Ernst P, Bhakat K, Crowe S. Acetylation of apurinic/apyrimidinic endonuclease-1 regulates Helicobacter pylori-mediated gastric epithelial cell apoptosis. Gastroenterology. 2009;136(7): 2258-69. PMID: 19505426 | PMCID: PMC2694750
- Gutierrez G, Tsuji T, Cross J, Davis R, Templeton D, Jiang W, Ronai Z. JNK-mediated phosphorylation of Cdc25C regulates cell cycle entry and G(2)/M DNA damage checkpoint. The Journal of biological chemistry. 2010;285(19): 14217-28. PMID: 20220133 | PMCID: PMC2863176
- Duane T, Scarcella N, Cross J, Wolfe L, Mayglothling J, Aboutanos M, Whelan J, Malhotra A, Ivatury R. Do flexion extension plain films facilitate treatment after trauma? The American surgeon. 2011;76(12): 1351-4. PMID: 21265348
- Lyons C, Victor K, Moshnikov S, Bachmann L, Baras A, Dettmann K, Cross J, Templeton D. PICquant: a quantitative platform to measure differential peptide abundance using dual-isotopic labeling with 12C6- and 13C6-phenyl isocyanate. Analytical chemistry. 2011;83(3): 856-65. PMID: 21192683 | PMCID: PMC3079250
- Victor K, Rady J, Cross J, Templeton D. Proteomic profile of reversible protein oxidation using PROP, purification of reversibly oxidized proteins. PloS one. 2012;7(2): e32527. PMID: 22389707 | PMCID: PMC3289665