• Primary Faculty Profiles
• Bankert, Richard, Ph.D., V.M.D., Professor
• Bianco, Piero, Ph.D., Associate Professor
• Campagnari, Anthony, Ph.D., Professor
• Collins, Arlene, Ph.D., Associate Professor
• Connell, Terry, Ph.D., Professor
• Egilmez, Nejat, Ph.D., Associate Professor
• Hakansson, Anders, Ph.D., Assistant Professor
• Hay, John, Ph.D., Professor
• Jacobs, Amy, Ph.D., Assistant Professor
• Melendy, Thomas, Ph.D., Associate Professor
• Panepinto, John, Ph.D., Assistant Professor
• Read, Laurie, Ph.D., Professor
• Russell, Michael, Ph.D., Professor
• Ruyechan, William, Ph.D., Professor and Chairman
• Thacore, Harshad, Ph.D., Associate Professor
• Williams, Noreen, Ph.D., Professor
• Adjunct Faculty Profiles
• Departmental Publications
• Career Opportunities
• The Witebsky Center
• Seminars

Faculty and Research

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Research Interests:

Our laboratory is focused on the DNA replication of Papillomaviruses and Polyomaviruses.

Papillomaviruses in particular are important human pathogens that cause disease ranging from the minor (hand and foot warts) to the major (sexually transmitted HPV, recurrent respiratory papillomatosis, and cervical and oropharyngeal cancers). While the recently available vaccine may help this problem (potentially up to a 70% decrease in cervical cancers), it does not prevent all HPV infections or cancers, and does not help individuals who are already infected. Treatments against HPV infection are needed. A common way of attacking viruses is by preventing viral genome replication. Our studies on HPV DNA replication are focused on identifying novel aspects of HPV DNA replication that can lead to new therapeutic targets. Specifically, we use a combination of biochemical, genetic, and pharmacological approaches to evaluate how the viral replication proteins pirate the cellular DNA replication apparatus to replicate their viral DNA Some of our recent work has focused on how the Papillomavirus replication proteins, E1 and E2, interact with and modulate the function of cellular replication proteins including: topoisomerase, the cellular ssDNA binding complex, and DNA polymerases. Any interactions that are found to be vital to HPV DNA replication provide new potential therapeutic targets.

We are also interested in basic mechanisms of how DNA is replicated and how this process is regulated. The complex regulatory nature of cellular DNA replication has made in vitro analysis of human DNA replication extremely difficult to study. In addition, the essential nature of cellular replication has limited capacity for genetic knock-out analysis. Polyoma and Papilloma viruses have neither of these constraints, so most of what we know about the biochemical mechanisms of the synthetic stages of human DNA replication comes from studies on Polyoma and Papilloma viruses. Our protein-protein interaction studies described above are providing novel insights into the basic processes of DNA replication. In addition, we also are interested in how DNA replication systems are regulated in response to DNA damage. We are currently studying the activation of the DNA damage kinase, ATR, and how it targets the viral DNA replication machinery to arrest DNA synthesis. ATR is an important kinase to study, as attenuation of ATR function is a very promising target for anti-cancer therapeutics.

For more detailed description of the activities in my laboratory go to www.smbs.buffalo.edu/wcmpi/faculty/melendy.html or
http://findadoc.med.buffalo.edu/profile/facultyprofile.asp?ht=fd&t=r&fid=0F70L4CPS or
www.buffalo.edu/president/200702-9aaas.html

Relevant references:

Loo, Y.-M., Melendy, T. (2004).  Recruitment of Replication Protein A by the Papillomavirus E1 Protein and Modulation by Single-Stranded DNA.  Journal of Virology.  78, 1605-1615.

Clower, R.V., Fisk, J.C., and Melendy, T. (2006).  Papillomavirus E1 protein binds to and stimulates human topoisomerase I.  Journal of Virology. 80, 1584-1587.

Liu, J.-S., Kuo, S.-R., and Melendy, T. (2006).  Phosphorylation of Replication Protein A by S Phase checkpoint kinases. DNA Repair. 5, 369-380.

Hu, Y., Clower, R.V., and Melendy, T.  (2006).  Cellular topoisomerase I modulates origin binding by bovine papillomavirus type 1 E1.  Journal of Virology 80, 4363-71.

Liu, J.-S., Kuo, S.-R., and Melendy, T. (2006). DNA damage-induced RPA Focalization is Independent of g-H2AX and RPA Hyper-phosphorylation. Journal of Cellular Biochemistry. 99, 1452-1462.

Masih, P.M., Kunnev, D., and Melendy, T. (2008).  Mismatch Repair Proteins are Recruited to Replicating DNA Through Interaction with PCNA. Nucleic Acids Research.  36, 67-75.