In order to properly conduct the studies of primary tumors as described in our proposal we will utilize our pathology facilities directed by Phillip Ruiz M.D./Ph.D. and the Hemato-pathology lab directed by Gerald Byrne, M.D.. The University of Miami Jackson Memorial medical center cares for a very large and diverse patient population. Our Pathology service has established NCI funded tissue banks in a variety of areas including breast cancer and HIV related malignancies. We have streamlined the processes for preserving residual tumor specimens and have IRB approved consents in place for the collection and storage of these valuable specimens. The success of our projects is dependent upon the availability of primary unmanipulated tumors that will be available for isolation, purification and analysis of RNA, protein and DNA Our tissue core will provide a central repository of neoplastic specimens (Adult T cell leukemia/ lymphoma) for use as outlined in the research component of our proposal. Our core leaders will provide expert histopathology review and molecular characterization of primary tumors that will be used in our proposal including a) viability studies on primary tumors b) special stains c) viral bio-marker studies d) specific flow cytometry assays and e) highly sensitive clonality assays. A principal function of the tissue core will be to supervise distribution of residual biopsy materials for the sole use of the investigators in this proposal. In order to verify initial data and plan future tissue based studies it will be necessary to maintain a bank of backup frozen specimens for designated use in these projects. As newer reagents and assays for molecular analysis become available through the Molecular Diagnostic and Characterization Core (MDCC), we will incorporate them into our portfolio where warranted. We will also work closely with the project leaders of the different components of this proposal as well as the MDCC to develop new technical approaches for the diagnosis and characterization of viral associated malignancies.

Public Health Relevance

The collection of tumor specimens related to this project is essential to ensure that the investigators are able to complete their proposed studies related to understanding mechanisms of viral-associated malignant disease. Such studies may enable the new design of diagnostics as well as treatments to combat cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA128115-05
Application #
8546188
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$83,217
Indirect Cost
$27,259
Name
University of Miami School of Medicine
Department
Type
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Bayraktar, Ulas Darda; Diaz, Luis A; Ashlock, Brittany et al. (2014) Zidovudine-based lytic-inducing chemotherapy for Epstein-Barr virus-related lymphomas. Leuk Lymphoma 55:786-94
Charoenthongtrakul, Soratree; Gao, Linlin; Parvatiyar, Kislay et al. (2013) RING finger protein 11 targets TBK1/IKKi kinases to inhibit antiviral signaling. PLoS One 8:e53717
Gao, Linlin; Harhaj, Edward William (2013) HSP90 protects the human T-cell leukemia virus type 1 (HTLV-1) tax oncoprotein from proteasomal degradation to support NF-*B activation and HTLV-1 replication. J Virol 87:13640-54
Lavorgna, Alfonso; Harhaj, Edward W (2013) Is there a role for ubiquitin or SUMO in human T-cell leukemia virus type 2 Tax-induced NF-*B activation? Future Virol 8:223-227
Shembade, Noula; Harhaj, Edward W (2012) Regulation of NF-?B signaling by the A20 deubiquitinase. Cell Mol Immunol 9:123-30
Harhaj, Edward W; Dixit, Vishva M (2012) Regulation of NF-*B by deubiquitinases. Immunol Rev 246:107-24
Lavorgna, Alfonso; Harhaj, Edward W (2012) EBV LMP1: New and shared pathways to NF-ýýB activation. Proc Natl Acad Sci U S A 109:2188-9
Ramos, Juan Carlos; Lossos, Izidore S (2011) Newly emerging therapies targeting viral-related lymphomas. Curr Oncol Rep 13:416-26
Charoenthongtrakul, Soratree; Zhou, Qinjie; Shembade, Noula et al. (2011) Human T cell leukemia virus type 1 Tax inhibits innate antiviral signaling via NF-kappaB-dependent induction of SOCS1. J Virol 85:6955-62
Harhaj, Edward W; Dixit, Vishva M (2011) Deubiquitinases in the regulation of NF-?B signaling. Cell Res 21:22-39

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