Bernard W Futscher

Bernard W Futscher

Assistant Research Scientist, Cancer Center Division
Associate Professor, BIO5 Institute
Investigator, Center for Toxicology
Professor, Pharmacology and Toxicology
Professor, Cancer Biology - GIDP
Primary Department
Department Affiliations
Contact
(520) 626-4646

Work Summary

Work Summary
Bernard Futscher's lab is studying the molecular origins of human cancer. Understanding epigenetic dysfunction in human cancer has been Dr. Futscher's primary research focus since establishing his own independent laboratory. This epigenetic research has moved into the area of noncoding RNAs and their potential role in cancer cell immortality.

Research Interest

Research Interest
Bernard Futscher, PhD, and his lab focus on the molecular origins of human cancer. More specifically, the lab group has 3 inter-related research objectives based on the underlying concept that developing an in-depth understanding of epigenetic mechanismsresponsible for governing cell fate will allow for the development of more effective strategies for the prevention, treatment, and cure of cancer. First, they wish to identify which epigenetic mechanisms participate in the transcriptional control of genes important to growth and differentiation. Second, they seek to determine how these epigenetic mechanisms, and therefore epigenetic homeostasis, become compromised during oncogenesis. Third, using a new and more complete understanding of epigenetic control of the genome, Dr. Futscher and his team are developing rational new therapeutic strategies that seek to repair these defects in the cancer cell and transcriptionally reprogram the malignant cancer cell to a benign state. To reach their objectives, a variety of in vitro models of cancer have been developed to address emerging hypotheses that are inferred from the literature in basic and clinical science as well as our own data. Results from these in vitro studies are then translated to the clinical situation to determine their meaning in the actual clinical face of the disease. Similarly, they attempt to take information obtained from the genome-wide assessment of clinical specimens in order to help guide our thinking and develop new hypotheses that can be tested experimentally in our in vitro models.

Publications

Jeixun, L. i., Hua, S. u., Chen, H., & Futscher, B. W. (2007). Optimal search-based gene subset selection for gene array cancer classification. IEEE Transactions on Information Technology in Biomedicine, 11(4), 398-405.
BIO5 Collaborators
Hsinchun Chen, Bernard W Futscher

PMID: 17674622;Abstract:

High dimensionality has been a major problem for gene array-based cancer classification. It is critical to identify marker genes for cancer diagnoses. We developed a framework of gene selection methods based on previous studies. This paper focuses on optimal search-based subset selection methods because they evaluate the group performance of genes and help to pinpoint global optimal set of marker genes. Notably, this paper is the first to introduce tabu search (TS) to gene selection from high-dimensional gene array data. Our comparative study of gene selection methods demonstrated the effectiveness of optimal search-based gene subset selection to identify cancer marker genes. TS was shown to be a promising tool for gene subset selection. © 2007 IEEE.

Futscher, B., Vrba, L., Jensen, T. J., Garbe, J. C., Heimark, R. L., Cress, A. E., Dickinson, S., Stampfer, M. R., & Futscher, B. W. (2010). Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. PloS one, 5(1).

The microRNA-200 family participates in the maintenance of an epithelial phenotype and loss of its expression can result in epithelial to mesenchymal transition (EMT). Furthermore, the loss of expression of miR-200 family members is linked to an aggressive cancer phenotype. Regulation of the miR-200 family expression in normal and cancer cells is not fully understood.

Fitzgerald, M., Oshiro, M., Holtan, N., Krager, K., Cullen, J. J., Futscher, B. W., & Domann, F. E. (2003). Human Pancreatic Carcinoma Cells Activate Maspin Expression Through Loss of Epigenetic Control. Neoplasia, 5(5), 427-436.

PMID: 14670180;PMCID: PMC1502613;Abstract:

The maspin gene is not expressed in normal human pancreas, but its expression is acquired during human pancreatic carcinogenesis. In other normal human cells and their malignant counterparts, maspin expression is controlled through the epigenetic state of its promoter. In studies presented herein, we used bisulfite genomic sequencing and chromatin immunoprecipitation studies to show that maspin-negative pancreas cells have a methylated maspin promoter, and that the associated H3 and H4 histones are hypoacetylated. In contrast to normal pancreas, four of six human pancreatic carcinoma cell lines investigated displayed activation of maspin expression. This activation of maspin expression in pancreatic carcinoma cells was linked to demethylated promoters and hyperacetylation of the associated H3 and H4 histones. In addition, 5-aza-2′-deoxycytidine treatments activated maspin expression in the two maspin-negative pancreatic carcinoma cell lines, suggesting a causal role for cytosine methylation in the maintenance of a transcriptionally silent maspin gene. Thus, human pancreatic carcinoma cells acquire maspin expression through epigenetic derepression of the maspin locus, and in so doing appear to co-opt a normal cellular mechanism for the regulation of this gene.

Pieper, R. O., Costello, J. F., Kroes, R. A., Futscher, B. W., Marathi, U., & Erickson, L. C. (1991). Direct correlation between methylation status and expression of the human O-6-methylguanine DNA methyltransferase gene. Cancer Communications, 3(8), 241-253.
Futscher, B. W., & Vrba, L. (2018). A suite of DNA methylation markers that can detect most common human cancers. Epigenetics.