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Scripps Research Joint Appointments

Faculty, Kellogg School of Science and Technology

Research Focus

The Disney laboratory develops rational methods to target RNA with small molecules.

Specific areas of interest are:

• Developing computational tools to target RNAs from sequence.
• Using multi-dimensional combinatorial screening (libraries vs libraries) to understand the chemical space (small molecule ligands) that is privileged for binding to RNA targets and the RNA structure space that is privileged for binding to small molecules.
• Rational design of small molecules targeting triplet repeating RNAs. Focus in this area is currently on targeting the RNAs that cause myotonic dystrophy types 1 and 2, which are type of muscular dystrophy that currently have no treatment.
• Structural biology of RNA: understanding the interplay of RNA structure and small molecule recognition of those structures.
• Rational design of novel antibacterials that target the bacterial ribosome and evade known modes of resistance.
• Synthetic organic chemistry: design and synthesis of small molecule libraries that are focused for binding RNA and in developing chemo-enzymatic routes to enable the synthesis of un-natural carbohydrates.

Education

Ph.D., Biophysical Chemistry, University of Rochester, 2003
B.S., Chemistry, University of Maryland, College Park, 1997
M.S., Chemistry, University of Rochester, 1999

Awards & Professional Activities

1995 – 1997- Howard Hughes Medical Institute Undergraduate Research Fellow; University of Maryland, College Park.
1997- Eric A. Batista Award; University of Maryland, College Park. Award for most outstanding undergraduate research.
1997 – 1999 - Sherman-Clark Memorial Fellow; University of Rochester.
2000 – 2001 - Elon Huntington Hooker Memorial Fellow; University of Rochester.
2001 – 2002 - Arnold Weissberger Memorial Fellow; University of Rochester.
June 2003 – May 2004 - Roche Foundation Post doctoral Fellowship; Swiss Federal Institute of Technology (ETH, Zürich).
June 2004 – January 2005 - Second Year Roche Foundation Post doctoral Fellowship; Swiss Federal Institute of Technology (ETH, Zürich).
September 2005 – August 2010 - Camille and Henry Dreyfus New Faculty Award.
July 2007 – June 2009 - NYSTAR JD Watson Young Investigator Award.
July 2008 – June 2010 - Research Corporation Cottrell Scholar Award.
May 2010 – April 2015 - Dreyfus Teacher-Scholar Award.
May 2010 - University at Buffalo, Excellent Scholar, Young Investigator Award.
2012 - David Gin Award in Carbohydrate Chemistry from the American Chemical Society in recognition of excellence in carbohydrate chemistry from a new investigator.
2013 - Eli Lilly Award in Biological Chemistry from American Chemical Society in recognition of outstanding research in biological chemistry of unusual merit and independence of thought and originality.

Selected References

A chemoenzymatic route to diversify aminoglycosides enables a microarray-based method to probe acetyltransferase activity (Cover article). Tsitovich PB, Pushechnikov A, French JM, Disney MD. Chembiochem 2010, 11:1656-1660.

Structure-activity relationships through sequencing (StARTS) defines optimal and suboptimal RNA motif targets for small molecules. Velagapudi SP, Seedhouse SJ, Disney MD. Angew Chem Int Ed Engl. , 2010, 49:3816-3818.

Controlling the specificity of modularly assembled small molecules for RNA via ligand module spacing: targeting the RNAs that cause myotonic muscular dystrophy. Lee MM, Childs-Disney JL, Pushechnikov A, French JM, Sobczak K, Thornton CA, Disney MD. J Am Chem Soc., 2009, 131: 17464-17472.

Rational design of ligands targeting triplet repeating transcripts that cause RNA dominant disease: application to myotonic muscular dystrophy type 1 and spinocerebellar ataxia type 3. Pushechnikov A, Lee MM, Childs-Disney JL, Sobczak K, French JM, Thornton CA, Disney MD. J Am Chem Soc. 2009 Jul 22:131(28):9767-79.

Links

Targeting RNA

Podcast on rational design of small molecules targeting RNAs that cause incurable disease

Rational design of small molecules targeting incruable disease II

Rational design of small molecules targeting incruable disease

Highlight of our work on targeting toxic RNAs III

Highlight of our work on targeting toxic RNAs II

Highlight of our work on targeting toxic RNAs

Highlight on our work to target RNA Defects in Huntington's and other diseases

Podcast on our work on developing drugs for Myotonic Muscular Dystrophy

Letting the Drugs Have Their Say

MMD Research: Blocking Harmful Interactions