Email Joshua Rosenthal
Phone: (508) 289-7253
Haverford College, B.A. Biology
Stanford University, Ph.D. Biology
Postdoctoral Scientist – Rosenthal Lab
Liscovitch-Brauer, N., Alon, S., Porath, H.T., Elstein, B., Unger, R., Ziv, T., Admon, A., Levanon, E.Y., Rosenthal, J.J.C.*, and Eisenberg, E.* (2017). Trade-off between transcriptome plasticity and genome evolution in cephalopods. Cell. (In press).
M.F. Montiel-Gonzalez, I.C. Vallecillo-Viejo, and J.J.C. Rosenthal (2016). An efficient system for selectively altering genetic information in mRNAs. NAR 44: e157.
S. Alon, S.C. Garrett, E.Y. Levanon, S. Olson, B.R. Graveley, J.J.C. Rosenthal, and E. Eisenberg (2015). The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing. eLife 4: 10.7554/eLife.05198.
M. Montiel-Gonzalez, I. Vallecillo, G. Yudowski, and J.J.C. Rosenthal (2013). Correction of mutations within the cystic fibrosis transmembrane conductance regulator by site-directed RNA editing. PNAS. 110: 18285-90.
J.J.C. Rosenthal and P.H. Seeburg (2012). A-to-I RNA Editing: Effects on Proteins Key to Neural Excitability. Neuron. 74:432-9.
S.C. Garrett and J.J.C. Rosenthal (2012). RNA editing underlies temperature adaptation in K+ channels from polar octopuses. Science. 335: 848-51.
In recent years, strategies to correct genetic mutations by modifying DNA and RNA molecules have received increasing attention. My project has been based on engineering a site-directed RNA editing strategy to use it as a tool to correct specific mistakes within mRNAs. RNA Editing is an enzymatic process that performs adenosine (A) to inosine (I) changes within RNAs. This process is catalyzed by Adenosine Deaminases that Act on RNA (ADARs). I is structurally similar to guanosine (G), and an A-to-I change is interpreted as an A-to-G change by ribosomes and other biological processes. As a result of this mechanism, protein function may be altered, particularly if editing occurs within mRNA coding regions. In the laboratory we have engineered an “editase” that can direct the editing process to a specific adenosine of our choosing (for a description of our strategy see R. Reenan New Engl J Med 370:172-174). Using this strategy, we have been able to correct a premature termination codon (PTC) mutation in an eGFP fluorescent reporter with a 70% of editing efficiency. At present, we are testing our strategy in several mutations that cause Cystic Fibrosis and can make corrections within cells at efficiencies ranging from 20% to 80%.
I am broadly interested in animal behavior, the underlying driving molecular mechanisms and their evolutionary context. The majority of my work has revolved around the tidal zone. During my MSc I studied the little known association between boxer crabs and the anemones they hold in their claws. This was a “classic” behavioral study, focused on host location, feeding habits and general natural history. Then during my PhD I focused on trying to understand tidal rhythmicity, using a limpet species as the model organism. I integrated both behavioral work in the field and lab, in conjuncture with a large transcriptomic project aimed at identifying potential tidal clock genes. At present I am a post-doc in the Rosenthal lab at MBL in Woods Hole. My work here focuses on the involvement of RNA editing in cephalopod rhythmicity and clock genes. Beside that I am fond of photography and cooking.
RNA editing is a universal process used by all metazoans to generate genetic diversity. In our lab, we study the most common form of editing mediated by the hydrolytic deamination of adenosines in RNAs. This process is catalysed by Adenosine Deaminases that Act on RNA (ADARs), a family of enzymes that convert Adenosines to Inosines in RNA. Inosine is a nucleoside that is structurally similar to guanosine and thus an A-to-I change is interpreted as an A-to-G change by the translational machinery. As a result of this mechanism, protein function may be altered as long as editing occurs in mRNA coding regions. From a therapeutic standpoint, RNA editing could be used as a tool in order to alter genetic information and change protein function. My project focuses on optimizing a strategy developed in our lab to manipulate the molecular machinery for RNA editing so that we can direct it to edit where we want. I am also interested in understanding the molecular basis for extensive editing in squid. Bioinformatics data has shown that squid RNA editing is robust, suggesting that there may be mechanistic differences underlying the editing process in this organism. I am currently studying the structure and function of squid RNA editing enzymes.