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Laboratory Research

PubMed Publications

Dermatology Research Laboratories
WIMR 1450, Room 7418
1111 Highland Ave.
Madison WI, 53705
608-263-4195
Fax: 608-263-5223
Email: Email to Vladimir Spiegelman

Vladimir Spiegelman, MD, PhD

Professor

Vladimir Spiegelman


Education
Medical School: Russian State Medical University, Moscow, Russia,1993
PhD: N.N.Blokhin Cancer Research Center, Moscow, Russia, 1995
Carcinogenesis, 1996-1997
Cancer Causation and Prevention, 1997-1998
PhD: N.N.Blokhin Cancer Research Center, Moscow, Russia, 1995

Our lab is focused on the understanding of molecular pathways and environmental factors that lead to development of human malignancies, and employment of newly acquired knowledge for eradication of cancer. Our research focuses on the mechanisms that govern the turnover of short-lived mRNAs that encode important regulators of cell proliferation, death and differentiation and the implications of this turnover for tumor development. The mechanisms regulating mRNA degradation, its alterations in human cancers and its potential ability of therapeutic modality are of primary interest.

In the series of recent manuscripts published in Nature (2006), and Oncogene (2008), Molecular Cell (2009), Cancer Research (2009), J. Biol. Chem. (2010), and Genes and Cancer (2010) our group established the role and mechanism of RNA-binding protein CRD-BP in the regulation of expression of several important regulators of tumorigenesis including βTrCP1, c-myc, Gli1, and MITF. CRD-BP is a novel transcriptional target gene of Wnt/β-catenin/Tcf and c-myc. CRD-BP protein is essential for induction of mRNA of βTrCP1, c-myc, Gli1, and MITF by β-catenin signaling in several human cancers. Furthermore, high levels of CRD-BP that are found in primary tumors exhibiting active β-catenin/Tcf signaling implicates CRD-BP induction in up-regulation of βTrCP1, activation of NF-kB suppression of apoptosis and resistance to chemotherapeutic agents in these diseases. Our lab continues to analyze the role that CRD-BP plays in the pathogenesis of variety of malignancies using in vitro and in vivo models. We also aim to identify novel mRNA targets of CRD-BP that are important for tumor progression, and look for the potential therapeutic ways of inhibiting the function of CRD-BP.

miRNAs are a class of genome-encoded small regulatory RNAs, that are largely known to base-pair with the 3’UTR of target mRNAs, down-regulating their stability and translation. Our group, however identified a functional miRNA-interacting motif within the coding region of human mRNA of βTrCP1. We were the first to comprehensively-characterize endogenous mRNA with functional mRNA-destabilizing miRNA-binding site in the coding region, shifting the current train of thought that 3’UTR is exclusively responsible for miRNA-dependent degradation of mRNAs. Our current work is aimed at analyzing the mechanisms of miRNA-dependent destabilization of mRNAs within coding regions.

 

 

 

From Molecular Cell Preview: Nielsen A.F., Gloggnitzer J. and Martinez J. MicroRNAs Cross the Line: The Battle for mRNA Stability Enters the Coding Sequence Molecular Cell Volume 35, Issue 2, 31 July 2009, Pages 139-140

 

 

 

 

Although miRNA-dependent modulation of the fate of mRNAs in cells emerged in recent years as a major mode of regulation of gene expression, little is known about positive and negative modulators of RISC. We have recently showed that CRD-BP protects mRNA of βTrCP1 and MITF from miRNA-directed degradation. Our current work is focused on the mechanisms by which CRD-BP protects mRNA from miRNA-directed degradation.


Last updated: September 16, 2014
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