Dr. Neilson is a trained developmental immunologist/mouse geneticist who has used the first portion of his postdoctoral fellowship in Phillip A. Sharp's lab at the the MIT Center for Cancer Research to gain a deeper understanding of short RNA biology, as well as to become facile with in vitro experimental approaches. Dr. Neilson's objective is to head an academic laboratory at a top research institution. During the mentored phase of the award period, Dr. Neilson aims to strengthen his exposure to the fields of biochemistry and bioinformatics. Training in the latter field in particular is increasingly important. During the mentored phase of the proposal, Dr. Neilson will generate mice with conditional alleles of the miR-92-1 locus. He will also initiate a biochemical characterization of the oncogenic miR-17-92 cluster as outlined in the proposal. Dr. Sharp's ability to mentor this mode of experimentation is unparalleled. Simultaneously, Dr. Neilson will take academic and non-academic courses to become fluent in programming and bioinformatic approaches, and teach an advanced undergraduate course in short RNAs and immunology. MIT and the Center for Cancer research have outstanding core facilities and academic resources relevant to these purposes. Once the mentored phase has been completed, Dr. Neilson and his trainees will continue the characterization of the mouse mutants proposed herein. Dr. Neilson's newly acquired biochemical and bioinformatic skill sets will be used in parallel with his existing knowledge of mammalian development and immunology to characterize the consequences of miR-92-1 disruption at the phenotypic, biochemical, and genomic levels. The consequences of miR-92-1 disruption in the context of the biochemical experiments performed during the mentored phase will be examined. The discovery of gene regulation by a new class of genes termed miRNAs has fundamentally changed the scientific view of how cells control gene expression. Several of these genes have been implicated in cancer. A detailed understanding how miRNAs work and how they themselves are controlled will allow a fuller comprehension of mammalian biology, at the same time enabling more effective exploitation of the pathway giving rise to these genes for therapeutic purposes (RNAi).

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Transition Award (R00)
Project #
5R00CA131474-05
Application #
8120353
Study Section
Subcommittee G - Education (NCI)
Program Officer
Strasburger, Jennifer
Project Start
2008-02-12
Project End
2013-02-28
Budget Start
2011-09-01
Budget End
2013-02-28
Support Year
5
Fiscal Year
2011
Total Cost
$241,531
Indirect Cost
Name
Baylor College of Medicine
Department
Physiology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Tan, Yuan-De; Deng, Jixin; Neilson, Joel R (2015) RAX2: a genome-wide detection method of condition-associated transcription variation. Nucleic Acids Res 43:e96
Tan, Yuan-De; Chandler, Anita M; Chaudhury, Arindam et al. (2015) A powerful statistical approach for large-scale differential transcription analysis. PLoS One 10:e0123658
Chaudhury, Arindam; Kongchan, Natee; Gengler, Jon P et al. (2014) A piggyBac-based reporter system for scalable in vitro and in vivo analysis of 3' untranslated region-mediated gene regulation. Nucleic Acids Res 42:e86
Zhao, P; Damerow, M S; Stern, P et al. (2013) CD44 promotes Kras-dependent lung adenocarcinoma. Oncogene 32:5186-90
Neilson, Joel R; Sandberg, Rickard (2010) Heterogeneity in mammalian RNA 3' end formation. Exp Cell Res 316:1357-64