Our program in Translational Research comprises a mix of basic and clinical scientists who apply their combined skills to do bench-to-bedside-to-bench research. This research paradigm has the greatest probability of generating new therapeutic approaches in the treatment of cancer. Research efforts include investigator-initiated clinical trials.

Our mission is to share knowledge, agents and resources to facilitate ongoing research projects, to facilitate community outreach and education, and to provide an interdisciplinary working group to formulate new approaches to diagnosis and treatment of solid tumors.

• The translational research group investigators are working with an array of solid tumor model systems to understand the molecular events that drive, and are critical for tumor progression and metastasis, and resistance to therapy. Organ cites under investigation are neoplasms of the: bladder, breast, head and neck, kidney, lung, ovary, pancreas and prostate.
• The basic science studies focus on identifying signal transduction targets, critical molecular pathways that are distinct in various tumor types.
• Preclinical and clinical studies focus on developing therapeutic interventions, and diagnostic markers to distinguish indolent vs. aggressive disease.

The long-term goals of this group are to identify novel targets that are critical for solid tumor progression and metastasis.

The underlying hypothesis that the group is collectively testing is that despite distinct origins, there are common targets among various solid tumor malignancies that could be explored to prevent tumor progression, tumor metastasis and therapeutic resistance.

The Protein Synthesis and Cancer group explores the role of translation in regulating tumor progression. This group studies the mechanism and regulation of protein synthesis in eukaryotic cells, with particular emphasis on how dysregulation of protein synthesis can lead to malignant transformation and progression to more aggressive forms of cell growth and invasion.

Members of this group are investigating the structure and function of translational machinery that might contribute to the cancer development and progression, such as:

1. Translation initiation (eIF4E) and elongation factors involved in selection of specific mRNA for translation
2. mRNA structures (cap, poly(A)) regulating stability of specific mRNAs
3. Non-classical secretion of aminoacyl-tRNA synthetases and their role in cancer
4. Signal transduction pathways that control the availability of eIF4E, especially those involving mTOR The goal of this focus group is to better understand how cancer cells become active and how to interfere with that process, which will lead to more specific treatment modalities.

Our program in Tumor Virology seeks to increase understanding of the roles played by oncogenic viruses in tumor development, thus stimulating novel approaches to prevention, diagnosis, treatment and cures for cancer.

This program that is funded in part by a large programmatic federal grant includes both basic and physician scientists. The group studies herpes viruses such as cytomegalovirus and the Epstein Barr Virus, which is causally associated with lymphomas, gastric carcinomas, and head and neck cancers, as well as small DNA tumor viruses such as polyoma and human papilloma viruses, which are responsible for cervical and anogenital cancers and head and neck cancers.

The common thread of this group is their conviction that chromatin - with its dynamic regulation and virtually limitless epigenetic complexity - significantly impacts gene transcription and DNA repair in cancer cells, thereby promoting cellular proliferation, invasiveness and metastasis characteristic of the malignant state.

In this regard, researchers are seeking to understand how human tumor viruses (Epstein Barr virus and papillomaviruses) induce epigenetic alterations to their own genomes as well as those of host cells. Such epigenetic modifications may regulate the expression of genes central to the viral lifecycle and ultimately, to the oncogenic state of the infected cells.

Additional researchers are investigating the role of chromatin in the regulation of transcription, with particular focus on the Cyp19A1 gene that encodes the protein aromatase that directly contributes to the malignancy of the majority of breast cancers. This research is conducted on a eukaryotic model of HSF1-regulated genes whose counterpart in human cancers is driven by a trascriptional program distinct from heat shock to support the highly malignant state. In addition, research about the way gene activation occurs in silent heterochromatin may provide insight into strategies for reactivation of tumor suppressor genes inappropriately silenced by heterochromatin.

Finally, our researchers are studying the role of chromatin and epigenetic modification in regulating the repair of double-stranded DNA breaks. One lab uses a novel episomal system in mammalian cells that permits purification of minichromosomes undergoing double-strand DNA repair for detailed chemical bioanalysis. The other lab studies double-stranded DNA breaks in human mitochondrial DNA whose chromatin structure and epigenetic character are very poorly understood.