个人简介
B.A., Case Western Reserve University
Ph.D., Case Western Reserve University
Postdoctorate, Medical Research Council Human Genetics Unit
研究领域
Post-transcriptional control of gene expression
Our work attempts to dissect the myriad roles of RNA binding proteins in mammalian gene expression. RNA processing reactions such as pre-mRNA splicing, mRNA export, translation and mRNA decay are influenced by the interplay of trans-acting proteins with their cognate cis-acting RNA elements. We believe that by elucidating the cis-acting RNA elements recognized by specific RNA binding proteins it will be possible to gain a better understanding of both the physiological relevance and mechanisms of action for these critical regulators of gene expression.
The experiments conducted by our group explore post-transcriptional gene regulation in the context of human cell culture, developmental and cancer models. We are currently studying the serine and arginine-rich family of pre-mRNA splicing factors (SR proteins) as well as the insulin-like growth factor II mRNA binding protein 3 (IMP-3). The SR proteins, like IMP-3 are linked to cellular transformation and tumor metastasis. We believe that analysis of these proteins will provide important insights to human disease as well as our basic understanding of mechanisms of gene regulation.
The laboratory employs a powerful genomic approach to map protein-RNA interactions occurring in the context of living cells. This stringent approach relies on recent advances in the area of ultra high-throughput DNA sequencing technology to identify individual binding sites within a complex pool of RNA transcripts. Computational approaches are required to transform the raw sequences into the genomic landscape recognized by each RNA binding protein. Specific hypotheses are then tested using a variety of cell-based and biochemical assays.
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HNRNPA1 promotes recognition of splice site decoys by U2AF2 in vivo.
Howard JM, Lin H, Wallace AJ, Kim G, Draper JM, Haeussler M, Katzman S, Toloue M, Liu Y, Sanford JR.
Genome Res. 2018 May;28(5):689-698. doi: 10.1101/gr.229062.117. Epub 2018 Apr 12.
The 3' end of the story: deciphering combinatorial interactions that control mRNA fate.
Sanford JR, Penalva LOF.
Genome Biol. 2017 Nov 29;18(1):227. doi: 10.1186/s13059-017-1360-6.
From mechanisms to therapy: RNA processing's impact on human genetics.
Penalva LO, Sanford JR.
Hum Genet. 2017 Sep;136(9):1013-1014. doi: 10.1007/s00439-017-1841-4. No abstract available.
Improved genome assembly of American alligator genome reveals conserved architecture of estrogen signaling.
Rice ES, Kohno S, John JS, Pham S, Howard J, Lareau LF, O'Connell BL, Hickey G, Armstrong J, Deran A, Fiddes I, Platt RN 2nd, Gresham C, McCarthy F, Kern C, Haan D, Phan T, Schmidt C, Sanford JR, Ray DA, Paten B, Guillette LJ Jr, Green RE.
Genome Res. 2017 May;27(5):686-696. doi: 10.1101/gr.213595.116. Epub 2017 Jan 30.
Modulation of nonsense mediated decay by rapamycin.
Martinez-Nunez RT, Wallace A, Coyne D, Jansson L, Rush M, Ennajdaoui H, Katzman S, Bailey J, Deinhardt K, Sanchez-Elsner T, Sanford JR.
Nucleic Acids Res. 2017 Apr 7;45(6):3448-3459. doi: 10.1093/nar/gkw1109.
Evaluation of Phosphorus Filter Media for an Inline Subsurface Drainage Treatment System.
Sanford JR, Larson RA.
J Environ Qual. 2016 Nov;45(6):1919-1925. doi: 10.2134/jeq2016.01.0038.
IGF2BP3 Modulates the Interaction of Invasion-Associated Transcripts with RISC.
Ennajdaoui H, Howard JM, Sterne-Weiler T, Jahanbani F, Coyne DJ, Uren PJ, Dargyte M, Katzman S, Draper JM, Wallace A, Cazarez O, Burns SC, Qiao M, Hinck L, Smith AD, Toloue MM, Blencowe BJ, Penalva LO, Sanford JR.
Cell Rep. 2016 May 31;15(9):1876-83. doi: 10.1016/j.celrep.2016.04.083. Epub 2016 May 19.
RNA-binding protein IGF2BP3 targeting of oncogenic transcripts promotes hematopoietic progenitor proliferation.
Palanichamy JK, Tran TM, Howard JM, Contreras JR, Fernando TR, Sterne-Weiler T, Katzman S, Toloue M, Yan W, Basso G, Pigazzi M, Sanford JR, Rao DS.
J Clin Invest. 2016 Apr 1;126(4):1495-511. doi: 10.1172/JCI80046. Epub 2016 Mar 14.