Green, Patrick

Patrick L. Green, PhD
Professor
Department of Veterinary Biosciences
The Ohio State University
327 Goss Laboratory
1925 Coffey Rd.
Columbus, Ohio 43210
Ph: (614) 688-4899
Fx: (614) 292-6473

Professional Training and Experience
- PhD, University of Wisconsin - McArdle Laboratory for Cancer Research
- Post-doctoral, University of California Los Angeles
- Assistant Research Biologist, University of California, Los Angeles
- Assistant Professor, Vanderbilt University
- Associate Professor, The Ohio State University
- Professor, The Ohio State University
- Director, Center for Retrovirus Research, The Ohio State University
- Codirector, Comprehensive Cancer Center Viral Oncogenesis Program

Research Interests
- Molecular Pathogenesis of Human T-cell Leukemia Virus (HTLV)
- Molecular Biology of Retrovirus Replication
- T-cell Activation/Transformation

Research Projects
The laboratory of Patrick Green is internationally recognized for their contributions to the understanding of the molecular basis of T-lymphocyte transformation and induction of leukemia/lymphoma and neurological disease by the human T-cell leukemia viruses (HTLVs). The Green lab has three areas of research focus investigating viral and cellular regulators of HTLV gene expression/replication, cellular transformation, and virus survival or persistence in the infected host.

Focus/Project 1
One aim of our laboratory is to understand mechanism(s) of post-transcriptional control of viral replication which is critical for HTLV persistence in the infected host. We have focused our studies on the HTLV regulatory protein Rex which is a critical on/off switch for viral replication and has been implicated in the transition from early-to-late phase of HTLV gene expression and potentially influences viral latency and long term survival in the infected host. We have discovered and are characterizing a novel carboxy terminal inhibitory domain of Rex that upon phosphorylation positively regulates Rex function. Mutational analysis and proteomic approaches are currently underway to precisely map key phosphorylated amino acid residues and to identify the cellular kinase/phoshatase involved. More recently we have discovered that one of the HTLV accessory proteins, HTLV-1 p30 and the related HTLV-2 p28, functions to repress viral replication by a novel post-transcriptional mechanism. These proteins specifically bind and retain the mRNA of key positive viral regulators in the nucleus leading to reduced protein expression and virion production.

Focus/Project 2
A second emphasis of our laboratory is to understand the mechanism(s) by which the HTLV Tax oncoprotein induces cellular transformation. These studies emphasize the use of full-length infectious molecular clones of HTLV-1 and the related less pathogenic HTLV-2, primary human T lymphocytes, and a rabbit animal model. Most recently we discovered that a PDZ binding motif in Tax plays an important role in micronuclei induction, primary T lymphocyte proliferation, and virus survival in the host. Along with collaborators, we showed that Tax via this motif binds the tumor suppressor protein hDLG and disrupts its natural function. We further showed that DLG knockdown by RNA interference increased the ability of Tax to transform a mouse T-cell line (CTLL-2) as measured by interleukin (IL)-2-independent growth directly confirming the role of the Tax-DLG interaction in the cellular transformation process.

Focus/Project 3
A third focus area of our laboratory is to understand the mechanism of action and biological role of a unique HTLV-1 accessory gene, termed Hbz. It is the only gene transcribed from the antisense strand of the viral genome and is expressed in almost all adult T-cell leukemia (ATL) cells, whereas tax oncogene expression is typically undetectable. We have discovered that HBZ is dispensable in cell culture, but is required to enhance virus replication and survival in the infected host. More recently utilizing a Hbz shRNA knockdown approach and NOD/SCID?c-/- (NOG) mice we discovered that Hbz expression enhances the proliferative capacity of HTLV-1 infected cells in culture and plays a critical role in infected cell survival and ultimately HTLV-1 tumorigenesis.

Publications (partial listing, 2006 - present)
Hernandez JM, Placek N, Floyd DH, Weilbaecher KN, Green PL, Boris-Lawrie K. Dr. Jekyll or Mr. Hyde in the AP-1 Family: Control mechanisms of JUND, a bipolar modulator of cell growth and maturation. Oncogene. In Press.

Matsuoka M, Watanabe T, Kannagi M, Bangham C, Grassmann R, Marriott SJ, Green PL, Jeang KT. Meeting report on the 13th International Conference on Human Retrovirology:Human T-cell leukemia virus research 30 years after adult T-cell leukemia. Cancer Research, 67:10638-10641, 2007.
 
Bolinger C, Hartman T, Yilmaz A, Kovacic M, Fernandez S, Ye J, Forget M, Green PL, Boris-Lawrie K: RNA helicase A is necessary for HTLV-1 replication and interacts with the 5'UTR of divergent lymphotropic retroviruses to facilitate Gag production. Nucleic Acid Res 35:2629-2642, 2007.

Li M, Green PL: Detection and Quantitation of HTLV-1 and HTLV-2 mRNA Species by Real-time RT-PCR. J Vir Meth, 142:159-168, 2007.

Twizere J-C, Spingael J-Y, Boxus M, Burny A, Dequiedt F, Dewulf J-F, Duchateau J, Portetelle D, Urbain P, Van Lint C, Green PL, Mahieux R, Parmentier M, Willems L,Kettmann L. Human T-cell leukemia virus type-1 Tax oncoprotein regulates G protein signalling, Blood 109: 1051-1060, 2007.

Ishioka K, Higuchi M, Takahashi M, Oie M, Tanaka Y, Takahashi S, Xie L, Green PL, Fujii M. Inactivation of tumor suppressor Dlg1 augments transformation of a T-cell line induced by human T-cell leukemia virus type 1 Tax protein. Retrovirology 3:71, 2006.

Arnold J, Younis I, Yamamoto B, Phipps AJ, Lairmore MD, Green PL: Enhancement of infectivity and persistence in vivo by HBZ, a natural antisense coded protein of HTLV-1 Blood 107:3976-3982, 2006.

Hiraragi H, Kim S-J,Phipps A, Silic-Benussi M, Ciminale V, Ratner L, Green PL, Lairmore MD: Human T-lymphotropic Virus Type 1 Mitochondria Localizing Protein p13II is Required for Viral Infectivity in vivo. J Virol 80:3469-3476, 2006.

Xie L, Yamamotto B, Haoudi A, Semmes OJ, Green PL: The PDZ domain of HTLV-1 Tax promotes virus mediated T-cell proliferation in vitro and persistence in vivo. Blood 107:1980-1988, 2006.

Younis I, Boris-Lawrie K, Green PL. Human T-cell leukemia virus ORF II p28 encodes a post-transcriptional repressor that is recruited at the level of transcription. J Virol 80:181-191, 2006.