Janet V. Cross, Ph.D.

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Janet V. Cross, Ph.D.

Janet V. Cross, Ph.D. Faculty Profile

 

Faculty photo - Cross

 

Janet V. Cross, Ph.D.

Assistant Professor of Pathology

 

Research Interests:

  • 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.

Publications

  • Cross, J.V. and D.J. Templeton (2004) Oxidative stress inhibits MEKK1 by site-specific glutathionylation in the ATP binding domain. Biochem. J. 381:675-83.

  • Zhang, C., D.M. Kenski, J.L. Paulson, A. Bonshtien, G. Sessa, J.V. Cross, D.J. Templeton and K.M. Shokat (2005)  A second-site suppressor strategy for chemical genetic analysis of diverse protein kinases. Nature Methods 2: 435-41.

  • Cross JV, Templeton DJ (2006) Regulation of signal transduction through protein cysteine oxidation.  Antioxid Redox Signal. 8:1819-27.

  • Cross J.V., F.W. Foss Jr, J.M. Rady, T.L. Macdonald, and D.J. Templeton (2007) The isothiocyanate class of bioactive nutrients covalently inhibit the MEKK1 protein kinase.  BMC Cancer 7:183.

 

A current list of Dr. Cross' journal publications can be obtained from PubMed.