Hashim al-Hashimi

Al-Hashimi was born in Beirut, Lebanon, and grew up in Greece, Italy, Jordan, and the UK.  As a graduate student at Yale, Al-Hashimi helped develop residual dipolar coupling methodology for the study of protein structure and dynamics by NMR.  As a postdoctoral fellow at the Memorial Sloan Kettering Cancer Center, Al-Hashimi expanded the domain of applicability of these methods to nucleic acids.  As a principal investigator, Al-Hashimi and his trainees discovered many of the ubiquitous motional modes underlying the biological activities of nucleic acids, with important implications for drug discovery and for understanding the mechanisms that cause genome instability and cancer.  These motions include transitions between Watson-Crick and Hoogsteen base pairs, which shape the DNA protein recognition and damage landscapes; transitions between mismatch and tautomeric/anionic Watson-Crick base pairs, which are responsible for errors during replication, transcription, and translation; motions that determine proper folding of RNA; and transient changes in RNA secondary structure that underlie gene regulation and viral genomic replication by non-coding RNAs.  His group developed methods harnessing the predictive power of RNA dynamic ensembles to identify small molecule inhibitors of HIV-1 replication.  In 2009, Al-Hashimi co-founded Base4 Inc to enable RNA-targeted drug discovery using RNA dynamics.