Thomas D. Friedrich, PhD
- University of Colorado1980PhD
Polyomaviruses are small DNA viruses that infect a wide range of mammalian and avian species. In most cases, mammalian polyomaviruses are nonpathogenic in normal hosts, but can be activated in the immunosuppressed state. Our laboratory studies two members of the polyomavirus family: Simian Virus 40 (SV40) was originally isolated from rhesus monkey kidney cells used to produce the polio vaccine and has been a valuable tool in defining mechanisms of mammalian transcription, replication and cell cycle control. BK virus (BKV) was initially isolated from a kidney transplant patient, but is present in most healthy humans beginning in early childhood. The recent use of highly effective immunosuppressive drugs following kidney transplantation has resulted in an increased incidence of BKV activation. BKV is now considered the major infectious threat to survival of transplanted kidneys. BKV is also associated with hemorrhagic cystitis (inflammation of the bladder) following bone marrow transplantation. Unfortunately, safe and effective antiviral drugs against BKV have not been identified.
Infection by SV40 or BKV stimulates quiescent kidney cells to initiate cellular DNA synthesis, providing an environment to support viral DNA replication. Both viruses also stimulate a host cell DNA damage response similar to that occurring after cell irradiation. We are interested in defining the molecular mechanisms of DNA damage response activation by SV40 or BKV and the role of the response in virus replication. Our research interests also extend to the identification of existing drugs and the development of novel compounds that will limit virus replication by inhibition of the DNA damage response, cell cycle regulatory pathways or viral gene products.
Nacro K, Zha C, Guzzo PR, Herr RJ, Peace D and Friedrich TD. 2007. Synthesis and topoisomerase poisoning activity of A-ring and E-ring substituted luotonin A derivatives. Bioorganic and Medicinal Chemistry 15: 4237-4246.
Trova MP, Barnes KD, Barford C, Benanti T, Bielaska M, Burry L, Lehman JM, Murphy C, O'Grady H, Peace D, Salamone S, Smith J, Snider P, Toporowski J, Tregay S, Wilson A, Wyle M, Zheng X, Friedrich TD. 2009. Biaryl purine derivatives as potent antiproliferative agents: Inhibitors of cyclin dependent kinases. Part I. Bioorganic and Medicinal Chemistry Letters 19: 6608-6612.
Trova MP, Barnes KD, Alicea L, Benanti T, Bielaska M, Bilotta J, Bliss B, Duong TN, Haydar S, Herr RJ, Hui Y, Johnson M, Lehman JM, Peace D, Rainka M, Snider P, Salamone S, Tregay S, Zheng X, Friedrich TD. 2009. Heterobiaryl purine derivatives as potent antiproliferative agents: Inhibitors of cyclin dependent kinases. Part II. Bioorganic and Medicinal Chemistry Letters 19: 6613-6617.