Research Interests Studies in my lab are primarily focused on understanding the molecular basis of HSV-1 capsid assembly and DNA packaging. To address the capsid assembly, we have developed procedures for using recombinant baculoviruses to produce HSV-1 capsids in insect cells. A panel of six different recombinant baculoviruses each expressing one of the six HSV-1 capsid genes was isolated. HSV-1 capsids of normal composition and structure were produced when insect cells were infected with the six viruses. The recombinant baculovirus system has allowed us to identify the minimal set of genes required for assembly of capsids. By using various combinations of these viruses and site directed mutagenesis to modify specific amino acid residues in the capsid proteins, it has been possible to define important interactions between capsid proteins. Our second area of interest focuses on the process of DNA cleavage and packaging within infected cell nuclei. Combining genetic and biochemical approaches, we have begun a study to identify functional domains of the cleavage/packaging proteins by introducing targeted mutations throughout their genes. The goal of these studies is to clarify how HSV-1 DNA is encapsidated and how the seven essential cleveage/packaging proteins participate in the encapsidation events. In addition, biochemical studies are being carried out to develop an in vitro system for HSV-1 DNA packaging. Such a system would facilitate more detailed analysis of the encapsidation process by providing the opportunity to manipulate the conditions of packaging outside an infected cell.   Selected Publications Huffman JB, Newcomb WW, Brown JC, Homa FL. Amino acids 143-150 of the herpes simplex virus Type 1 scaffold protein are required for the formation of portal-containing capsids.J Virol. 2008 Apr 16. Trus BL, Newcomb WW, Cheng N, Cardone G, Marekov L, Homa FL, Brown JC, Steven AC. Allosteric signaling and a nuclear exit strategy: Binding of UL25/UL17 heterodimers to DNA-filled HSV-1 capsids. Mol Cell. 2007 May 25;26(4):479-489. Jacobson JG, Yang K, Baines JD, Homa FL. Linker insertion mutations in the herpes simplex virus type 1 UL28 gene: effects on UL28 interaction with UL15 and UL33 and identification of a second-site mutation in the UL15 gene that suppresses a lethal UL28 mutation. J Virol. 2006 Dec;80(24):12312-23. Newcomb WW, Homa FL, Brown JC. Herpes simplex virus capsid structure: DNA packaging protein UL25 is located on the external surface of the capsid near the vertices. J Virol. 2006 Jul;80(13):6286-94. Liu S, Knafles JD, Chang JS, Waszak GA, Baldwin ET, Deibel MR Jr, Thomsen DR, Homa FL, Wells PA, Tory MC, Poorman RA, Gao H, Qiu X, Seddon AP. Crystal structure of the herpes simplex 1 virus DNA polymerase. J Biol Chem. 2006 Apr 24; Complete Publication Listing   Grant Support NIH/NIAID: Herpes simplex virus capsid assembly and DNA packaging 2005-2010. Principal Investigator: F. L. Homa. Ph.D.   Other Links MGB Faculty Webpage University of Pittsburgh

Fred L. Homa, Ph.D. Office:  BSTWR - W1256 Lab:BSTWR - E1202 Phone:412-648-8788 Fax: 412-624-1401 flhoma@pitt.edu   Academic Affiliations Associate Professor Univ. of Pittsburgh School of Medicine Dept. of Microbiology and Molecular Genetics Member, Biochemistry and Molecular Genetics Graduate Program University of Pittsburgh 1988-2003 Research Scientist Pharmacia/Upjohn Company Kalamazoo, MI   Education 1975 B.A. Biology North Central College 1982 Ph.D. Biological Chemistry Univ. of Illinois Medical School Chicago, IL 1982-1988 Postdoctoral Fellow Department of Human Genetics University of Michigan Medical School 1985-1988 Senior Postdoctoral Scholar Department of Human Genetics University of Michigan Medical School   Lab Personnel Graduate Student: Shelley Cockrell Research Specialist: Jamie Huffman Lab Phone: 412/383-8637