Two challenges in drug discovery are (1) finding the targets that, when modulated, will treat or cure a disease and (2) finding the therapies that modulate those targets. We are a computational team that takes an integrative approach to target discovery while innovating the new modalities to drug those targets. A new modality of focus is RNA as a target; the exploitation of a weak link in the fate of an RNA for the treatment of a disease. To find the weak link we use statistical and advanced methods to bring together transcriptomics, proteomics, ribosome profiling, eCLIP, and other NGS or proprietary data. In doing so, we learn about which RNA-protein interactions, splicing changes, translation start sites, etc. can be modulated to effect the target. Partnership is key and we collaborate with experts across data science, chemistry, biophysics, genomics, high throughput screening, biology, chemoproteomics, and more.
SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice Palacino J, Swalley SE, Song C, Cheung AK, Shu L, Zhang X, Van Hoosear M, Shin Y, Chin DN, Keller CG, Beibel M, Renaud NA, Smith TM, Salcius M, Shi X, Hild M, Servais R, Jain M, Deng L, Bullock C, McLellan M, Schuierer S, Murphy L, Blommers MJ, Blaustein C, Berenshteyn F, Lacoste A, Thomas JR, Roma G, Michaud GA, Tseng BS, Porter JA, Myer VE, Tallarico JA, Hamann LG, Curtis D, Fishman MC, Dietrich WF, Dales NA, Sivasankaran R. Nat Chem Biol. 2015 Jul;11(7):511-7