Ryan L. Boudreau, PhD

Portrait
Assistant Professor of Internal Medicine - Cardiovascular Medicine

Contact Information

Education

PhD, Molecular Physiology & Biophysics, The University of Iowa

Post Doctoral Fellow, The University of Iowa

Research Summary

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.

Publications

Spengler, R. M., Zhang, X., Cheng, C., McLendon, J. M., Skeie, J. M., Johnson, F. L., Davidson, B. L. & Boudreau, R. L. (2016). Elucidation of transcriptome-wide microRNA binding sites in human cardiac tissues by Ago2 HITS-CLIP. Nucleic acids research, 44(15), 7120-31. PMID: 27418678.

Piedrahita, D., Castro-Alvarez, J. F., Boudreau, R. L., Villegas-Lanau, A., Kosik, K. S., Gallego-Gomez, J. C. & Cardona-Gómez, G. P. (2015). ß-Secretase 1's Targeting Reduces Hyperphosphorilated Tau, Implying Autophagy Actors in 3xTg-AD Mice. Frontiers in cellular neuroscience, 9, 498. PMID: 26778963.

Madhavan, L., Daley, B. F., Davidson, B. L., Boudreau, R. L., Lipton, J. W., Cole-Strauss, A., Steece-Collier, K. & Collier, T. J. (2015). Sonic Hedgehog Controls the Phenotypic Fate and Therapeutic Efficacy of Grafted Neural Precursor Cells in a Model of Nigrostriatal Neurodegeneration. PloS one, 10(9), e0137136. PMID: 26340267.

Rasmussen, T. P., Wu, Y., Joiner, M. L., Koval, O. M., Wilson, N. R., Luczak, E. D., Wang, Q., Chen, B., Gao, Z., Zhu, Z., Wagner, B. A., Soto, J., McCormick, M. L., Kutschke, W., Weiss, R. M., Yu, L., Boudreau, R. L., Abel, E. D., Zhan, F., Spitz, D. R., Buettner, G. R., Song, L. S., Zingman, L. V. & Anderson, M. E. (2015). Inhibition of MCU forces extramitochondrial adaptations governing physiological and pathological stress responses in heart. Proceedings of the National Academy of Sciences of the United States of America, 112(29), 9129-34. PMID: 26153425.

Monteys, A. M., Wilson, M. J., Boudreau, R. L., Spengler, R. M. & Davidson, B. L. (2015). Artificial miRNAs Targeting Mutant Huntingtin Show Preferential Silencing In Vitro and In Vivo. Molecular therapy. Nucleic acids, 4, e234. PMID: 25849618.

Boudreau, R. L., Jiang, P., Gilmore, B. L., Spengler, R. M., Tirabassi, R., Nelson, J. A., Ross, C. A., Xing, Y. & Davidson, B. L. (2014). Transcriptome-wide discovery of microRNA binding sites in human brain. Neuron, 81(2), 294-305. PMID: 24389009.

Keiser, M. S., Boudreau, R. L. & Davidson, B. L. (2014). Broad therapeutic benefit after RNAi expression vector delivery to deep cerebellar nuclei: implications for spinocerebellar ataxia type 1 therapy. Molecular therapy : the journal of the American Society of Gene Therapy, 22(3), 588-95. PMID: 24419082.

Ramachandran, P. S., Boudreau, R. L., Schaefer, K. A., La Spada, A. R. & Davidson, B. L. (2014). Nonallele specific silencing of ataxin-7 improves disease phenotypes in a mouse model of SCA7. Molecular therapy : the journal of the American Society of Gene Therapy, 22(9), 1635-42. PMID: 24930601.

Gross, T. J., Powers, L. S., Boudreau, R. L., Brink, B., Reisetter, A., Goel, K., Gerke, A. K., Hassan, I. H. & Monick, M. M. (2014). A microRNA processing defect in smokers' macrophages is linked to SUMOylation of the endonuclease DICER. The Journal of biological chemistry, 289(18), 12823-34. PMID: 24668803.

Boudreau, R. L., Jiang, P., Gilmore, B. L., Spengler, R. M., Tirabassi, R., Nelson, J. A., Ross, C. A., Xing, Y. & Davidson, B. L. (2014). Transcriptome-wide discovery of miRNA binding sites in human brain. Neuron, 81(2), 294-301.

Ramachandran, P. S., Bhattarai, S., Singh, P., Boudreau, R. L., Thompson, S., Laspada, A. R., Drack, A. V. & Davidson, B. L. (2014). RNA interference-based therapy for spinocerebellar ataxia type 7 retinal degeneration. PloS one, 9(4), e95362. PMID: 24759684.

Lee, J. H., Sowada, M. J., Boudreau, R. L., Aerts, A. M., Thedens, D. R., Nopoulos, P. & Davidson, B. L. (2014). Rhes suppression enhances disease phenotypes in Huntington's disease mice. Journal of Huntington's disease, 3(1), 65-71. PMID: 25062765.

Boudreau, R. L., Spengler, R. M. & Davidson, B. L. (2013). siSPOTR: a tool for designing highly specific and potent siRNAs in human and mouse. Nucleic Acids Research, 41(1), e9.

Keiser, M. S., Geoghegan, J. C., Boudreau, R. L., Lennox, K. A. & Davidson, B. L. (2013). RNAi or overexpression: alternative therapies for Spinocerebellar Ataxia Type 1. Neurobiology of disease, 56, 6-13. PMID: 23583610.

Boudreau, R. L., Davidson, B. L. (2012). Generation of hairpin-based RNAi vectors for biological and therapeutic application. Methods in enzymology, 507, 275-96. PMID: 22365779.

López-Tobón, A., Castro-Álvarez, J. F., Piedrahita, D., Boudreau, R. L., Gallego-Gómez, J. C. & Cardona-Gómez, G. P. (2011). Silencing of CDK5 as potential therapy for Alzheimer's disease. Reviews in the neurosciences, 22(2), 143-52. PMID: 21476938.

Spencer, N. Y., Yan, Z., Boudreau, R. L., Zhang, Y., Luo, M., Li, Q., Tian, X., Shah, A. M., Davisson, R. L., Davidson, B., Banfi, B. & Engelhardt, J. F. (2011). Control of hepatic nuclear superoxide production by glucose 6-phosphate dehydrogenase and NADPH oxidase-4. The Journal of biological chemistry, 286(11), 8977-87. PMID: 21212270.

Boudreau, R. L., Rodríguez-Lebrón, E. & Davidson, B. L. (2011). RNAi medicine for the brain: progresses and challenges. Human molecular genetics, 20(R1), R21-7. PMID: 21459775.

McBride, J. L., Pitzer, M. R., Boudreau, R. L., Dufour, B., Hobbs, T., Ojeda, S. R. & Davidson, B. L. (2011). Preclinical safety of RNAi-mediated HTT suppression in the rhesus macaque as a potential therapy for Huntington's disease. Molecular therapy : the journal of the American Society of Gene Therapy, 19(12), 2152-62. PMID: 22031240.

Boudreau, R. L., Spengler, R. M. & Davidson, B. L. (2011). Rational design of therapeutic siRNAs: minimizing off-targeting potential to improve the safety of RNAi therapy for Huntington's disease. Molecular therapy : the journal of the American Society of Gene Therapy, 19(12), 2169-77. PMID: 21952166.

Piedrahita, D., Hernández, I., López-Tobón, A., Fedorov, D., Obara, B., Manjunath, B. S., Boudreau, R. L., Davidson, B., Laferla, F., Gallego-Gómez, J. C., Kosik, K. S. & Cardona-Gómez, G. P. (2010). Silencing of CDK5 reduces neurofibrillary tangles in transgenic alzheimer's mice. The Journal of neuroscience : the official journal of the Society for Neuroscience, 30(42), 13966-76. PMID: 20962218.

Boudreau, R. L., Davidson, B. L. (2010). RNAi therapeutics for CNS disorders. Brain research, 1338, 112-21. PMID: 20307511.

Boudreau, R. L., Martins, I. & Davidson, B. L. (2009). Artificial microRNAs as siRNA shuttles: improved safety as compared to shRNAs in vitro and in vivo. Molecular Therapy, 17(1), 169-175.

Boudreau, R. L., McBride, J. L., Martins, I., Shen, S., Xing, Y., Carter, B. J. & Davidson, B. L. (2009). Non-allele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington’s disease mice. Molecular Therapy, 17(6), 1053-1063.

Boudreau, R. L., McBride, J. L., Martins, I., Shen, S., Xing, Y., Carter, B. J. & Davidson, B. L. (2009). Nonallele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington's disease mice. Molecular therapy : the journal of the American Society of Gene Therapy, 17(6), 1053-63. PMID: 19240687.

Boudreau, R. L. (2008). Minimizing variables among hairpin-based RNAi vectors reveals improved potency of shRNAs. RNA, 14(9), 1834-1844.

McBride, J. L., Boudreau, R. L., Harper, S. Q., Staber, P. D., Monteys, A. M., Martins, I., Gilmore, B. L., Burstein, H., Peluso, R. W., Polisky, B., Carter, B. J. & Davidson, B. L. (2008). Artificial miRNAs mitigate shRNA-mediated toxicity in the brain: implications for the therapeutic development of RNAi. Proceedings of the National Academy of Sciences of the United States of America, 105(15), 5868-73. PMID: 18398004.

Davidson, B. L., Boudreau, R. L. (2007). RNA interference: a tool for querying nervous system function and an emerging therapy. Neuron, 53(6), 781-8. PMID: 17359914.

Boudreau, R. L., Davidson, B. L. (2006). RNAi therapy for neurodegenerative diseases. Current topics in developmental biology, 75, 73-92. PMID: 16984810.