Department of Microbiology, Biochemistry and Molecular Genetics
David Lukac, Ph.D.
B.S. 1990, Rutgers University, New Brunswick, NJ
Ph.D. 1997, University of Pennsylvania School of Medicine, Philadelphia, PA
Post-doc, 2000, University of California, San Francisco School of Medicine
Ph.D., 1997, University of Pennsylvania School of Medicine, Molecular Virology
|Guito, J.; Lukac, D.M. (2015) KSHV Reactivation and Novel Implications of Protein Isomerization on Lytic Switch Control. Viruses 7: 72-109. http://www.mdpi.com/1999-4915/7/1/72|
|Guito, J, A Gavina, D Palmeri, and DM Lukac (2014). The cellular peptidyl-prolyl cis/trans isomerase Pin1 regulates reactivation of Kaposi's sarcoma-associated herpesvirus from latency. J Virol 88:547- 558. http://jvi.asm.org/content/88/1/547.full|
|Shin, HJ, DeCotiis, J, Giron, M, Palmeri, D and DM Lukac. (2014), “Histone Deacetylase Classes I and II Regulate Kaposi’s Sarcoma-Associated Herpesvirus Reactivation.” J Virol 88:1281-1292. http://jvi.asm.org/content/88/2/1281.full|
|Guito, J, DM Lukac Kaposi’s sarcoma-associated herpesvirus Rta Promoter Specification and Viral Reactivation. (Invited Review) Frontiers in Microbiology 3:30. (2012).|
|Palmeri, D, Carroll, KD, Gonzalez-Lopez, O, and DM Lukac. Kaposi’s sarcoma-associated herpesvirus Rta tetramers make high affinity interactions with repetitive DNA elements in the Mta promoter to stimulate DNA binding of RBP-Jk/CSL. Journal of Virology 85: 11901-11915. (2011).|
|Spadavecchia, S., Gonzalez-Lopez, O., Carroll KD, Palmeri, D, and DM Lukac Convergence of Kaposi's Sarcoma- Associated Herpesvirus Reactivation with Epstein-Barr Virus Latency and Cellular Growth Mediated by the Notch Signaling Pathway in Coinfected Cells , Journal of Virology 84: 10488-10500. (2010).|
|Bu, W, D Palmeri, R Krishnan, R Marin, VM Aris, P Soteropoulos, and DM Lukac. Identification of Direct Transcriptional Targets of the Kaposi’s sarcoma-associated herpesvirus (KSHV) Rta Lytic Switch Protein by conditional nuclear localization of Rta. Journal of Virology 82: 10709-10723. (2008).|
|Carroll, KD, F Khadim, S Spadavecchia, D Palmeri, and DM Lukac. Direct interactions of Kaposi’s sarcoma- associated herpesvirus/Human herpesvirus-8 ORF50/Rta protein with the cellular protein Octamer-1 and DNA are critical for specifiying transactivation of a delayed-early promoter and viral reactivation. Journal of Virology 81 (16): 8451–8467. (2007).|
|Carroll, KD, W Bu, D Palmeri, S Spadavecchia, S J. Lynch, S A. E. Marras, S Tyagi, and DM Lukac. The Kaposi’s sarcoma-associated herpesvirus lytic switch protein stimulates DNA binding of RBP-Jk/CSL to activate the Notch pathway. Journal of Virology 80 (19) 9697-9709. (2006).|
|Liang, Y., S.J. Lynch, J. Chang, D.M. Lukac, and D. Ganem. The lytic switch protein of KSHV activates gene expression via functional interaction with RBP-Jk, the target of the Notch signaling pathway. Genes and Development 16: 1977-89. (2002) .|
Infection and Host Response is an intensive course in which much information must be communicated in a relatively short period of time. Attendance at all lectures is highly recommended. Students will receive basic information through lectures and small group case discussions. They will be expected to assimilate and use the information presented. On-line laboratories will emphasize the properties of infectious agents and histopathology of infectious disease. Students participate in two types of small group case discussions. POPS (Patient-Oriented Problem Solving) cases are group-led and students will receive a grade based on their participation. Small group infectious disease cases are led by 4th year medical students. Attendance will be taken at all these sessions and preparation and participation will be graded. The course is divided into three units. Each unit ends with a unit exam. At the end of the course, there is a comprehensive subject examination (Shelf).
Host-virus interactions in oncogenic herpesviral infection
Kaposi's Sarcoma-Associated Herpesvirus (KSHV; also known as Human herpesvirus-8) is a DNA tumor virus that is the etiologic agent of Kaposi's Sarcoma and other AIDS-related cancers. Epidemiologic studies have demonstrated that lytic reactivation of KSHV from latency is required for progression of these unique cancers. We are studying the critical host-virus interactions, at the molecular level, that govern reactivation of the virus, in order to gain a thorough understanding of the pathogenesis of KSHV infection.
We have previously demonstrated that a single viral protein, called Rta (for "replication and transcriptional activator"), functions as a molecular switch controlling the induction of the virus from latency. For these studies, we have developed a number of quantitative assays for measuring viral reactivation and replication in response to various proteins and stimuli. We have also determined that Rta's critical role in reactivation is to transcriptionally transactivate viral and cellular promoters in combination with other host and viral proteins. We have identified two of these cellular proteins, and we are characterizing the DNA/protein interactions that are critical for viral reactivation. We are also deciphering Rta's function by investigating its mechanisms of interaction with heterologous viral proteins. Finally, we are committed to determining the molecular regulation of progression of the viral lytic cycle in which many of the viral oncogenes are expressed.