Director Hari K Koul, PhD, FACN, FASN,
|FWCC Basic and Translational Research aims to make cancer a manageable chronic condition
“While complete cure may not be an immediate practical goal, in the near future, we must strive to make cancer a manageable chronic condition, where people can live almost full and productive lives, despite a diagnosis of cancer” Hari K Koul, PhD, Dec 2013
Basic and translational science programs contribute to comprehensive care at Feist-Weiller Cancer Center. The mission of the scientific programs in the Division of Basic and Translational Research is to increase our understanding of the mechanisms that regulate cancer formation and progression, and to develop novel techniques to detect and treat cancer. Four scientific programs facilitate patient care at Feist-Weiller Cancer Center. These are the Program in Translational Research, the Focus groups in Cancer Cell Biology, the Program in Tumor Virology, and the Innovative North Louisiana Experimental Therapeutics (INLET) Program.
Program in Translational Cancer Research
Director Hari K Koul, PhD, 318.675.5161
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. 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 mission of this group 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.
Cancer Biology Focus Groups:
1. Protein Synthesis and Cancer Focus Group
Leader Nadejda Korneeva, PhD, 318.865.6963
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.
2. Epigenetic Regulation of Gene Expression and DNA Repair in Cancer Focus Group
Leader David Gross, PhD, 318.675.5027
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, two labs (Bodily and Scott) 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. Two other labs (Pruitt and Gross) 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, two other labs (De Benedetti and Harrison) study 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.
Program in Tumor Virology
Leader Lindsey Hutt-Fletcher, PhD, 318.675.4948
The 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 herpesviruses 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.
Innovative North Louisiana Experimental Therapeutics (INLET)
Director James Cardelli, PhD, 318.675.5756
INLET is a multi-institutional program focused on the discovery and development of a wide range of drugs that affect multiple diseases in humans, including cancer, diabetes, fungal infection and neurological disorders. The long range goal is to commercialize drugs to treat human disease and increase economic development along the I-20 corridor. INLET members at different locations bring expertise about assay development, screening, drug design and delivery, a variety of in vitro and in vivo models of cancer, pharmacology and toxicology, as well as early clinical development strategies for the discovery of new small molecule therapies. The INLET screening center is equipped with liquid handlers, robotic screening devices and high content, real time screening/assay platforms (Cellomics and the Essen Bioscience Incucyte). Research performed at this screening center includes independent research, federally-supported research and company-sponsored research programs. INLET is developing partnerships with several academic institutions, business experts and pharmaceutical companies to aid in moving drugs from the discovery phase through commercialization.