Affiliate Professor of Chemistry

Office: 327C Padnos
Phone: 331-8633
Email: [email protected]

Education/Professional Training
B.S. Biology, Cornell University
Ph.D. Chemistry, University of Maryland
Postdoctoral, NIST/CARB

Research Interests

Snake envenomation has been identified as a neglected tropical disease by the World Health Organization (WHO), and globally results in approximately 130,000 death/yr and 500,000 amputations/yr.¹ The major components found in many viperidae snake venoms are metalloprotienases that bring about acute and often severe tissue necrosis and hemorrhage.  Several examples of natural inhibitory proteins have been demonstrated, none more widely studied than those found in opossum species from the Didelphis genus.^2,3 We are currently using a molecular biology and bio-organic approach to better understand the specific structural features required by these inhibitors with the potential of developing medically relevant treatment for viperidae envenomenation. My research group has cloned the gene found in the N. American opossum (D. virginiana) that encodes for the SVMPI called “oprin” into an expression vector to make large quantities of this protein in E. coli bacteria.⁴ The main approach to expressing these inhibitory proteins involves cloning opossum DNA into an expression vector that appends a “purification tag” called maltose binding protein (MBP) that simplifies purification. Once purified, these inhibitory proteins can be evaluated for inhibitory activity and their 3-D structure can be determined.  We use recombinant DNA techniques, protein purification and fluorescence inhibitor assays in my group to characterize the structure and activity of these protein inhibitors.  The main goal of this work is to develop proteins and/or synthetic peptide analogs that will serve as a first-line medical treatment upon viperidae envenomation to reduce tissue necrosis and hemorrhage to prevent amputations or death.

References

1. Gutiérrez, J. M. et al. Snakebite envenoming. Nat. Rev. Dis. Primers  2017, 3, 17063.

2. Werner, R.M., Vick, J.A., Resistance of the opossum (Didelphis Virginiana) to envenomation by snakes of the family Crotalidae. Toxicon 1977, 15, 29-32.

3. Rocha, S.L., Neves-Ferreira, A.G., Trugilho, M.R., Chapeaurouge, A., Leon, I.R., Valente, R.H., Domont, G.B., Perales, J., Crotalid snake venom subproteomes unraveled by the antiophidic protein DM43. Journal of Proteome Research 2009, 8, 2351-2360.

4. Werner, R.M., Miling, L., Elliott, B. Hawes, M., Webber, D., Wickens, J.  Bacterial expression of a snake venom metalloproteinase inhibitory protein from the North American opossum (D. virginiana).  Toxicon  2021, 194, 1-10.