Department of biochemistry and Molecular biology
Daniel Fernandes, PhD, DSc
Biochemistry and Molecular Biology
1977-1980 Postdoctoral Research Fellow, U.S.P.H.S., (laboratory of J.R. Bertino, M.D.),
Dept of Pharmacology, Yale University School of Medicine
1990 D.Sc. (Honorary), University of Massachusetts, North Dartmouth, MA
1978 Ph.D. (Pharmacology), The George Washington University, Washington, D.C.
1970-1972 Georgeotwn University School of Dentistry, Washington, D.C.
1970 B.S. (Biology and Chemistry), Providence College, Providence, Rhode Island
The expression of amplified genes is associated with the initiation and progression of cancers as well as the development of tumor cell resistance to anticancer drugs. A major goal of my laboratory is to determine the biochemical mechanism involved in gene amplification. We are testing the hypothesis that alterations in the synthesis of DNA intermediates required for DNA replication are early biochemical events that lead to the amplification of the oncogenes and certain drug resistance genes. Future studies are aimed at developing new therapies that can prevent the emergence of malignant and drug resistance phenotypes by blocking gene amplification. Specifically, we are testing the ability of fludarabine, an inhibitor of DNA replication, to block the amplification of the Mdr-1 and Pgp genes and prevent the subsequent development of drug resistance in patients having acute myelogeneous leukemia. DNA topoisomerases are enzymes that regulate the degree of DNA supercoiling in the cell. In a second major project we are testing the hypotheses that topoisomerase I and topoisomerase II poisons irreversibly damage DNA by inducing double-strand breaks in replication forks on the nuclear matrix. The cleaved replication forks then detach from the nuclear matrix, which induces DNA disorganization and apoptosis. Subsequent studies are aimed at identifying the cellular events that signal apoptosis and DNA repair following drug-induced damage to replicating DNA.
Recent Publications | Additional Publications
Ishimaru D, Zuraw L, Ramalingam S, Sengupta TK, Bandyopadhyay S, Reuben A, Fernandes DJ, Spicer EK. Mechanism of regulation of Bcl-2 mRNA by nucleolin and A+U rich element binding factor 1 (AUF1). J Biol Chem. 2010 Jun 22. [Epub ahead of print] PubMed PMID: 20571027.
Ishimaru D, Ramalingam S, Sengupta TK, Bandyopadhyay S, Dellis S, Tholanikunnel BG, Fernandes DJ, Spicer EK. Regulation of Bcl-2 expression by HuR in HL60 leukemia cells and A431 carcinoma cells. Mol Cancer Res. 2009 Aug;7(8):1354-66. Epub 2009 Aug 11. PubMed PMID: 19671677.
Soundararajan S, Wang L, Sridharan V, Chen W, Courtenay-Luck N, Jones D, Spicer EK, Fernandes DJ. Plasma membrane nucleolin is a receptor for the anticancer aptamer AS1411 in MV4-11 leukemia cells. Mol Pharmacol. 2009 Nov;76(5):984-91. Epub 2009 Aug 5. PubMed PMID: 19657047; PubMed Central PMCID: PMC2774992.