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Timothy M. Rose, Ph.D.

My research interests lie in the identification and characterization of DNA herpesviruses implicated in cellular transformation and tumor induction, and in the study of host and viral proteins and cytokines which mediate these effects. In particular, we are studying the viral etiology of Kaposi's sarcoma (KS) and other AIDS-related malignancies with regards to the interactions between viruses (retroviruses and herpesviruses) and cytokines in virus activation and tumor induction. We have discovered and are characterizing two new herpesviruses which are homologs of Kaposi's sarcoma-associated herpesvirus (KSHV) in two macaque species. The macaque viruses are associated with a Kaposi's sarcoma-like malignancy, retroperitoneal fibromatosis (RF), which like AIDS-KS is also associated with a retrovirus infection, simian retrovirus 2. Ongoing projects include the cloning and sequence comparison of regions of the new human and macaque herpesviruses, the search for transformation- and latency-related genes and cytokine inducing genes in these viruses, and the development of the macaque system as an animal model for studying KS in humans. We have also been involved in the discovery and characterization of a human cytokine called oncostatin M (OSM) which plays a role in embryonic, hematopoietic and neuronal differentiation. We have cloned the OSM gene and have characterized its chromosomal locus, and are studying the expression of the OSM gene during normal development and in neoplastic diseases. OSM has been shown to be the major autocrine/paracrine growth factor for KS and cloning studies have shown that KSHV has captured an OSM/IL6-like gene which binds the same receptor as OSM. We are currently studying the involvement of OSM and other cytokines in fibroproliferative malignancies such as KS and RF. We have also developed a novel technique using consensus-degenerate hybrid oligonucleotide primers for the identification of distantly related genes. We have used this technique to discover the macaque herpesviruses described above, as well as to identify other novel retroviruses and herpesviruses. Finally, I have a strong interest in bioinformatics and have developed a “Biological Information Resource’ for the researchers at the University. For this resource, sequence analysis software has been developed and DNA and protein databases are maintained for bioinformatics research.