Allan M. Gurtan
Massachusetts Institute of Technology
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Publication
Featured researches published by Allan M. Gurtan.
Journal of Molecular Biology | 2013
Allan M. Gurtan; Phillip A. Sharp
MicroRNAs (miRNAs) are key regulators of gene expression. They are conserved across species, expressed across cell types, and active against a large proportion of the transcriptome. The sequence-complementary mechanism of miRNA activity exploits combinatorial diversity, a property conducive to network-wide regulation of gene expression, and functional evidence supporting this hypothesized systems-level role has steadily begun to accumulate. The emerging models are exciting and will yield deep insight into the regulatory architecture of biology. However, because of the technical challenges facing the network-based study of miRNAs, many gaps remain. Here, we review mammalian miRNAs by describing recent advances in understanding their molecular activity and network-wide function.
Cancer Cell | 2012
Arvind Ravi; Allan M. Gurtan; Madhu S. Kumar; Arjun Bhutkar; Christine Chin; Victoria Lu; Jacqueline A. Lees; Tyler Jacks; Phillip A. Sharp
MicroRNAs are a class of short ~22 nucleotide RNAs predicted to regulate nearly half of all protein coding genes, including many involved in basal cellular processes and organismal development. Although a global reduction in miRNAs is commonly observed in various human tumors, complete loss has not been documented, suggesting an essential function for miRNAs in tumorigenesis. Here we present the finding that transformed or immortalized Dicer1 null somatic cells can be isolated readily in vitro, maintain the characteristics of DICER1-expressing controls and remain stably proliferative. Furthermore, Dicer1 null cells from a sarcoma cell line, though depleted of miRNAs, are competent for tumor formation. Hence, miRNA levels in cancer may be maintained in vivo by a complex stabilizing selection in the intratumoral environment.
Genes & Development | 2013
Allan M. Gurtan; Arvind Ravi; Peter B. Rahl; Andrew D. Bosson; Courtney K. JnBaptiste; Arjun Bhutkar; Charles A. Whittaker; Richard A. Young; Phillip A. Sharp
MicroRNAs (miRNAs) are critical to proliferation, differentiation, and development. Here, we characterize gene expression in murine Dicer-null adult mesenchymal stem cell lines, a fibroblast cell type. Loss of Dicer leads to derepression of let-7 targets at levels that exceed 10-fold to 100-fold with increases in transcription. Direct and indirect targets of this miRNA belong to a mid-gestation embryonic program that encompasses known oncofetal genes as well as oncogenes not previously associated with an embryonic state. Surprisingly, this mid-gestation program represents a distinct period that occurs between the pluripotent state of the inner cell mass at embryonic day 3.5 (E3.5) and the induction of let-7 upon differentiation at E10.5. Within this mid-gestation program, we characterize the let-7 target Nr6a1, an embryonic transcriptional repressor that regulates gene expression in adult fibroblasts following miRNA loss. In total, let-7 is required for the continual suppression of embryonic gene expression in adult cells, a mechanism that may underlie its tumor-suppressive function.
Genes & Development | 2017
Courtney K. JnBaptiste; Allan M. Gurtan; Kevin K. Thai; Victoria Lu; Arjun Bhutkar; Mei-Ju Su; Asaf Rotem; Tyler Jacks; Phillip A. Sharp
MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression critical for organismal viability. Changes in miRNA activity are common in cancer, but how these changes relate to subsequent alterations in transcription and the process of tumorigenesis is not well understood. Here, we report a deep transcriptional, oncogenic network regulated by miRNAs. We present analysis of the gene expression and phenotypic changes associated with global miRNA restoration in miRNA-deficient fibroblasts. This analysis uncovers a miRNA-repressed network containing oncofetal genes Imp1, Imp2, and Imp3 (Imp1-3) that is up-regulated primarily transcriptionally >100-fold upon Dicer loss and is resistant to resilencing by complete restoration of miRNA activity. This Dicer-resistant epigenetic switch confers tumorigenicity to these cells. Let-7 targets Imp1-3 are required for this tumorigenicity and feed back to reinforce and sustain expression of the oncogenic network. Together, these Dicer-resistant genes constitute an mRNA expression signature that is present in numerous human cancers and is associated with poor survival.
RNA | 2012
Allan M. Gurtan; Victoria Lu; Arjun Bhutkar; Phillip A. Sharp
Cell Reports | 2016
Sara J. C. Gosline; Allan M. Gurtan; Courtney K. JnBaptiste; Andrew D. Bosson; Pamela Milani; Simona Dalin; Bryan J. Matthews; Yoon Sing Yap; Phillip A. Sharp; Ernest Fraenkel
The FASEB Journal | 2015
Courtney K. JnBaptiste; Allan M. Gurtan; Victoria Lu; Arjun Bhutkar; Phillip A. Sharp
Elsevier | 2015
Allan M. Gurtan; Courtney K. JnBaptiste; Andrew D. Bosson; Pamela Milani; Bryan J. Matthews; Yoon Sing Yap; Phillip A. Sharp; Ernest Fraenkel; Sara Jane Calafell Gosline; Simona Dalin
Cancer Research | 2015
Sara J. C. Gosline; Allan M. Gurtan; Courtney K. JnBaptiste; Andrew D. Bosson; Pamela Milani; Simona Dalin; Bryan J. Matthews; Yoon Sing Yap; Phillip A. Sharp; Ernest Fraenkel
Elsevier | 2012
Arvind Ravi; Allan M. Gurtan; Madhu S. Kumar; Christine Chin; Victoria Lu; Phillip A. Sharp; Arjun Bhutkar; Jacqueline A. Lees; Tyler Jacks