Molecular Recognition in Biological Systems and Bioinformatics

Biochemistry; Pharmacology; Molecular Biology; Bioinformatics.

Our main research interest is the role of oxovanadium compounds in cellular metabolism. Vanadium is a trace metal which is required for growth in algae and bacteria but can also be cytotoxic. Oral administration of oxovanadium compounds alleviates the symptoms of Diabetes in animal models and humans. Part of the therapeutic effect of Vanadium compounds involves inhibition of protein tyrosine phosphatases in the insulin signaling pathway via a transition state analogue mechanism. We have also demonstrated the importance of interactions of vanadium with cellular redox properties in the therapeutic action of vanadium. Our research also includes the insulin-like effect of other transition metals in an effort to better understand the mechanism of vanadium action in alleviating the symptoms of diabetes. The major focus of the laboratory is to characterize the role of vanadium in physiological processes. Work is ongoing in characterizing the effects of vanadium in cell culture systems including stimulation of apoptosis and differentiation. We hope to extend our studies to metabonomics in order to better understand why some diabetic animals respond to vanadium treatment and some do not respond.

Humans, rats, yeast

• Insulin-mimetic properties of Transition metals (Vanadium)
• Metal (Vanadium) Toxicity
• Role of Metals (Vanadium) in physiological processes

• Growth Inhibition Assays
• QPCR
• Tunnel Assays for Apoptosis
• Microarrays
• STZ diabetic rat model

• HepG2
• L6
• HII4E
• 3T3 L1

• ⁵¹V-NMR
• EPR

• Diabetes
• Cancer

Muscle, liver

Tracey, A., Willsky, G. R., Takeuchi, E. R. (2007) Vanadium: Chemistry, Biochemistry, Pharmacology and Technical Applications, (Boca Raton FL: CRC Press) 250 pages.

Willsky, Gail R., Godzalla, Michael E. III, Kostyniak, Paul J., Chi, Lai-Har, Gupta, Rohit, Yuen, Violet G., McNeill, John H., Mahroof-Tahir, Mohammad, Smee, Jason J., Yan, Luqin, Lobernick, Aaron, Watson, Shari and Crans, Debbie C., (2007) Comparing Administration Route in Rats with Streptozicin-Induced Diabetes and Inhibition of Myoblast Growth of Vanadium [V(III), V(IV) and V(V)] Dipicolinic Acid Complexes. ACS Symposium Series 974 Vanadium 93-109.

Smee, Jason J., Epps, Jason A., Teissedre, Guillaume, Maes, Mandy, Harding, Nichola, Yang, Luqin, Baruah, Bharat, Miller, Susie M., Anderson, Oren P., Willsky, Gail R., Crans, Debbie C. (2007) 4-Amino- and 4-Nitrodipicolinatovanadium(V) Complexes and Their Hydroxylamido Derivatives: Synthesis, Aqueous, and Solid-State Properties. Inorganic Chemistry 46 9827-9840.

Gail R. Willsky, Lai-Har Chi, Yulan Liang, Daniel P. Gaile, Zihua Hu and Debbie C. Crans (2006) Diabetes Altered Gene Expression in Rat Skeletal Muscle Corrected by Oral Administration of Vanadyl Sulfate Physiol Genomics 26:192-201.

Hu, Zihua; Willsky, Gail R.. (2006) Utilization of two sample t-test statistics from redundant probe sets to evaluate different probe set algorithms in GeneChip studies. BMC Bioinformatics 7:12 doi:10.1186/147-2105-7-12 (online journal)

Péter Buglyó, Debbie C. Crans Eszter M. Nagy, Ruby Lisa Lindo, Luqin Yang, Jason J. Smee,Wenzheng Jin, Lai-Har Chi, Michael E. Godzala III, and Gail R. Willsky (2005) Aqueous Chemistry of the VanadiumIII and the VIII-Dipicolinate Systems and a Comparison of the Effect of Three Oxidation States of Vanadium Compounds on Diabetic Hyperglycemia in Rats Inorganic Chemistry 44: 5416-5427.

Crans, D.C., Yang L.,. Alfano, J.A., Chi, Wenzheng, L.H., Mahroof-Tahir, M.J., Robbins, K., Toloue, M.M., Chan, L.K., Plante A.J., Grayson, R.Z., and Willsky, G.R., (2003) (4-hydroxypyridine-2,6-dicarboxylato) oxovanadate(V) - A New Insulin-Like Compound: Chemistry: Effects on Myoblast and Yeast Cell Growth and Effects on Hyperglycemia in Rats with STZ-induced Diabetes. Coord. Chem. Rev. 237: 13-22.

G.R. Willsky, A.B. Goldfine, P.J. Kostyniak, L.Q. Yang, H.R. Khan and D.C. Crans. (2001) Effect of vanadium (IV) compounds in the treatment of diabetes: in vivo and in vitro studies with vanadyl sulfate and Bis(maltolato)oxovanadium (IV). J. Inorg. Bioch. 85: 33-42.

Goldfine, A.B., M-E. Patti, L.Zuberi, B.J. Goldstein, R.LeBlanc, E.J.Landaker, Z.Y. Jiang, G. R. Willsky and C.R. Kahn (2000) Metabolic Effects of Vanadyl Sulfate in Humans with Non-Insulin-Dependent Diabetes Mellitus: In Vivo and In Vitro Studies. Metabolism 49: 400-410.