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
(520) 626-4646
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
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.


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.

Vrba, L., Junk, D. J., Novak, P., & Futscher, B. W. (2008). p53 induces distinct epigenetic states at its direct target promoters. BMC Genomics, 9.

PMID: 18922183;PMCID: PMC2585595;Abstract:

Background: The tumor suppressor protein p53 is a transcription factor that is mutated in many cancers. Regulation of gene expression by binding of wild-type p53 to its target sites is accompanied by changes in epigenetic marks like histone acetylation. We studied DNA binding and epigenetic changes induced by wild-type and mutant p53 in non-malignant hTERT-immortalized human mammary epithelial cells overexpressing either wild-type p53 or one of four p53 mutants (R175H, R249S, R273H and R280K) on a wild-type p53 background. Results: Using chromatin immunoprecipitation coupled to a 13,000 human promoter microarray, we found that wild-type p53 bound 197 promoters on the microarray including known and novel p53 targets. Of these p53 targets only 20% showed a concomitant increase in histone acetylation, which was linked to increased gene expression, while 80% of targets showed no changes in histone acetylation. We did not observe any decreases in histone acetylation in genes directly bound by wild-type p53. DNA binding in samples expressing mutant p53 was reduced over 95% relative to wild-type p53 and very few changes in histone acetylation and no changes in DNA methylation were observed in mutant p53 expressing samples. Conclusion: We conclude that wild-type p53 induces transcription of target genes by binding to DNA and differential induction of histone acetylation at target promoters. Several new wild-type p53 target genes, including DGKZ, FBXO22 and GDF9, were found. DNA binding of wild-type p53 is highly compromised if mutant p53 is present due to interaction of both p53 forms resulting in no direct effect on epigenetic marks. © 2008 Vrba et al; licensee BioMed Central Ltd.

Severson, P. L., & Futscher, B. W. (2012). Epigenomic Actions of Environmental Arsenicals. Toxicology and Epigenetics, 129-148.
Watts, G. S., & Futscher, B. W. (1995). Detecting differences in 5-methylcytosine using restriction enzyme isoschizomers: An endogenous control for complete digestion. Nucleic Acids Research, 23(22), 4740-4741.

PMID: 8524671;PMCID: PMC307454;

Futscher, B. W., Foley, N. E., Gleason-Guzman, M. C., Meltzer, P. S., Sullivan, D. M., & Dalton, W. S. (1996). Verapamil suppresses the emergence of P-glycoprotein-mediated multi-drug resistance. International Journal of Cancer, 66(4), 520-525.

PMID: 8635868;Abstract:

Selection protocols were designed to determine whether non-cytotoxic chemomodifiers can influence the evolution of the drug-resistant phenotype. To this end, the human multiple myeloma cell line RPMI 8226 (8226/S) was selected with either doxorubicin, verapamil or doxorubicin plus verapamil. Using this approach low-level multi-drug-resistant (MDR) cell lines were obtained when 8226/S was selected with doxorubicin only or doxorubicin plus verapamil but not with verapamil only. The MDR phenotypes obtained were mechanistically distinct. In doxorubicin only-selected cells (8226/dox4), drug resistance was mediated by over-expression of the MDRI gene and its cognate protein P-glycoprotein. In contrast, the drug resistance seen in the doxorubicin plus verapamil-selected cells was mediated through decreases in topoisomerase II protein levels and catalytic activity and not by P-glycoprotein over-expression. Cells selected with verapamil alone did not become resistant to any of the drugs tested. None of the 3 selected cell lines showed any changes in MRP gene expression when compared with 8226/S. Our results indicate that the inclusion of verapamil during drug selection with doxorubicin influences the drug-resistant phenotype by preventing the selection of MDR I/P-glycoprotein-positive cells.