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Paul Ogg


paul-ogg@uiowa.edu
Mentor: Richard Roller, Ph.D.
Lab Phone: 335-7664

Characterization of the anti-apoptotic activity of the HSV-1 Us3 encoded protein kinase.

Over 80% of the adult US population is infected with Herpes Simplex Virus Type-1 (HSV-1). 20% of the infected individuals suffer recurrent reactivation of the virus in the form of painful lesions, called cold sores, around the oral cavity. The Roller laboratory is studying the anti-apoptotic activity of a virally encoded protein kinase named Us3. A recent publication demonstrated that Us3 is sufficient to block apoptosis induced by overexpression of Bad (a member of the Bcl-2 family of apoptotic regulators). Inhibition of apoptosis correlated with phosphorylation of Bad on two serines that fall within consensus sequences recognized by Us3. Phosphorylation of Bad by Akt (also called Protein Kinase B) on these two serines has previously been shown to block Bad apoptotic activity. Data generated by our laboratory demonstrated that Us3 can block apoptosis induced by a variety of Bcl-2 family members, including Bax and Bid. Furthermore, we demonstrated that Us3 could block apoptosis induced by a non-phosphorylatable form of Bad. These data suggest that Us3 blocks apoptosis downstream of apoptotic events that occur at the mitochondria. We are presently exploring the possibility that Us3 blocks apoptosis by regulating the activity of caspases. Reports that describe mice infected with a Us3 deletion virus suggest that Us3 is critical for pathogenesis. Identification of cellular factors regulated by Us3 may facilitate the development of drugs used to treat HSV infections.

Abstracts:

Ogg PD Ryckman BJ Knudson CM Roller RJ. The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members. CSH Meeting on Programmed Cell Death. #201. Sept 17-21, 2003.

Publications:

Ogg PD, McDonell PJ, Ryckman BJ, Knudson CM, Roller RJ. The HSV-1 Us3 protein kinase is sufficient to block apoptosis induced by overexpression of a variety of Bcl-2 family members. Virology. 2004 Feb 20;319(2):212-24. PMID: 14980482



Honors and Awards

  • Jakobsen Graduate Student Forum, Top Prize, 2002. Jakobsen Graduate Student Forum, Honorable Mentio
  • Health Sciences Microbiology Laboratory, Instructor, 1999. Health Sciences Microbiology Laboratory,
  • American Association for the Advancement of Science Member; Mensa, International Member
  • Ogg PD Ryckman BJ Knudson CM Roller RJ. The HSV-1 Us3 protein kinase is sufficient to block apoptosi