My laboratory studies post-transcriptional responses in diseased and developing heart and brain using viral vectors, mouse models, human tissues, and cell culture systems. Our goal is to identify disease-related RNA-binding proteins (RBPs) and microRNAs (miRNAs) and determine their regulatory targets using computational and high-throughput biochemical means (HITS-CLIP, CLIP-seq). RBPs and miRNAs are key mediators of post-transcriptional responses, and modulation of their activities provides attractive means to manipulate gene expression for therapeutic benefit. Another major aspect of my laboratory’s research involves determining how human genetic variations contribute to disease by altering post-transcriptional regulatory mechanisms. This work aims to generate valuable resources (e.g. miRNA target interactomes in human tissues) to accelerate our understanding of miRNA and RBP functions in heart and brain and facilitate the translation of available and ongoing genetic studies towards novel or refined disease mechanisms and therapies.
In addition to this, we are also investigating the functions of several novel genes, including long non-coding RNAs, in heart and brain. These projects incorporate a breadth of techniques, including viral-based (AAV) overexpression and inhibition (RNAi) of genes in vivo, generation and characterization of CRISPR-derived knockout mice, and gene transfer and functional assays in human iPS-derived cells.
Overall, my research program is balanced in basic and translational studies, wet-lab and computational methods, and resource- and hypothesis-driven research. This framework promotes multi-disciplinary and collaborative science, offering an excellent environment to foster the growth of current and future trainees.
Assistant Research Scientist
The Next Best Thing in Cardiovascular Research: Highlights From the Basic Cardiovascular Sciences Scientific Sessions. Boudreau RL. J Am Heart Assoc. 2017 Sep 20;6(9). pii: e007245. doi: 10.1161/JAHA.117.007245.
Decreased KCNE2 Expression Participates in the Development of Cardiac Hypertrophy by Regulation of Calcineurin-NFAT (Nuclear Factor of Activated T Cells) and Mitogen-Activated Protein Kinase Pathways. Liu W, Deng J, Ding W, Wang G, Shen Y, Zheng J, Zhang X, Luo Y, Lv C, Wang Y, Chen L, Yan D, Boudreau RL, Song LS, Liu J. Circ Heart Fail. 2017 Jun;10(6). pii: e003960. doi: 10.1161/CIRCHEARTFAILURE.117.003960.
RNA Interference of Human α-Synuclein in Mouse. Kim YC, Miller A, Lins LC, Han SW, Keiser MS, Boudreau RL, Davidson BL, Narayanan NS. Front Neurol. 2017 Jan 31;8:13. doi: 10.3389/fneur.2017.00013. eCollection 2017.
Sirtuin 1 regulates cardiac electrical activity by deacetylating the cardiac sodium channel. Vikram A, Lewarchik CM, Yoon JY, Naqvi A, Kumar S, Morgan GM, Jacobs JS, Li Q, Kim YR, Kassan M, Liu J, Gabani M, Kumar A, Mehdi H, Zhu X, Guan X, Kutschke W, Zhang X, Boudreau RL, Dai S, Matasic DS, Jung SB, Margulies KB, Kumar V, Bachschmid MM, London B, Irani K. Nat Med. 2017 Mar;23(3):361-367. doi: 10.1038/nm.4284. Epub 2017 Feb 13.
Elucidation of transcriptome-wide microRNA binding sites in human cardiac tissues by Ago2 HITS-CLIP. Spengler RM, Zhang X, Cheng C, McLendon JM, Skeie JM, Johnson FL, Davidson BL, Boudreau RL. Nucleic Acids Res. 2016 Sep 6;44(15):7120-31. doi: 10.1093/nar/gkw640. Epub 2016 Jul 14.
β-Secretase 1's Targeting Reduces Hyperphosphorilated Tau, Implying Autophagy Actors in 3xTg-AD Mice. Piedrahita D, Castro-Alvarez JF, Boudreau RL, Villegas-Lanau A, Kosik KS, Gallego-Gomez JC, Cardona-Gómez GP. Front Cell Neurosci. 2016 Jan 8;9:498. doi: 10.3389/fncel.2015.00498. eCollection 2015.