Allan Jacobson, PhD
Professor and Chair, Department of Microbiology and Physiological Systems
Gerald L. & Zelda S. Haidak Distinguished Professor of Cell Biology
Allan Jacobson, Ph.D., is a founding member of the UMass Chan Medical School’s faculty, Chair of the Department of Microbiology and Physiological Systems, and the Gerald L. Haidak and Zelda S. Haidak Distinguished Professor of Cell Biology. He is also a member of the Medical School’s RNA Therapeutics Institute and the Li Weibo Institute for Rare Diseases Research.
Dr. Jacobson discovered, named, and has characterized in detail the crucial post-transcriptional regulatory mechanism known as NMD, or nonsense-mediated mRNA decay. Prior to his work it was assumed that the instability of mRNAs derived from genes harboring nonsense mutations reflected ribosome release at premature termination codons (PTCs) and subsequent targeting of presumably exposed regions of mRNA by non-specific ribonucleases. Jacobson’s research transformed this simplistic notion by demonstrating that the yeast UPF1 gene is the central regulator of a pathway (NMD) that specifically controls the stability of PTC-containing mRNAs. His lab has identified and characterized the interactions and functions of NMD’s factors, demonstrated NMD’s requirement for ongoing translation and PTC recognition by the ribosome, and defined a substantial set of endogenous NMD substrates, many of which entered the pathway as a consequence of translational errors. Identification of this diverse set of substrates led to the understanding that NMD is a probabilistic quality control pathway operating during the elongation phase of protein synthesis. Most importantly, Jacobson demonstrated that mechanistic differences between premature and normal translation termination were the basis for NMD and could be explained by the proximity of normal termination events to 3’-UTR-associated stimulatory factors. This breakthrough yielded a pioneering approach to treating genetic disorders when Jacobson and his collaborator, Stuart Peltz, co-founded PTC Therapeutics Inc. to develop a translation termination readthrough drug as therapy for genetic disorders caused by nonsense mutations. That drug (ataluren/Translarna) is a highly successful first-in-class treatment for nonsense mutation Duchenne Muscular Dystrophy patients in over 40 countries worldwide.
Dr. Jacobson is a recipient of the UMass Chan Faculty Achievement Award for Outstanding Teaching, the Dean’s Award for Outstanding Contribution to Graduate Education, and the Chancellor’s Medal for Distinguished Scholarship. He is also a recipient of an American Cancer Society Faculty Research Award and an NIH MERIT Award, and is an elected member of the American Academy of Arts and Sciences and the American Academy of Microbiology.
Meet AJ
AJ making sense out of nonsense, a "Voices of UMASSMED" podcast:
https://soundcloud.com/umasschan/jacobson-update
AJ on serendipity in science:
https://www.youtube.com/watch?v=MrEd_1Tky_E
AJ on genetic nonsense, from bench to bedside:
https://www.youtube.com/watch?v=45QmcZVSLdo