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Brett Winborn


brtwinborn@aol.com
Mentor: Henry Paulson, M.D./Ph.D.
The Paulson lab studies the molecular mechanisms of neurodegenerative diseases. There are nine neurodegenerative diseases caused by a trinucleotide CAG expansion encoding an elongated polyglutamine region, with each disease affecting a different protein. My focus is on Spinocerebellar Ataxia Type III (SCA3), in which the protein Ataxin-3 is affected. The expanded polyglutamine region causes protein misfolding and aggregation, although the exact mechanism of cell death is not well understood. Preliminary evidence suggests that Ataxin-3 is involved in the ubiquitin-proteosome pathway (UPP). My goal is to elucidate the function of wildtype Ataxin-3 and any deleterious effects of the expanded protein. My current research involves the study of Ataxin-3 as a deubiquitinating enzyme with a role in the UPP. More extensive knowledge of the function of Ataxin-3 could lead to therapies for SCA3 and possibly other polyglutamine diseases.



Todi SV, Winborn BJ, Scaglione KM, Blount JR, Travis SM, Paulson HL. Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin-3. EMBO J. 2009 Feb 18;28(4):372-82. Epub 2009 Jan 15. PubMed PMID:19153604; PubMed Central PMCID: PMC2646149.

Winborn BJ, Travis SM, Todi SV, Scaglione KM, Xu P, Williams AJ, Cohen RE, Peng J, Paulson HL. The deubiquitinating enzyme ataxin-3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains. J Biol Chem. 2008 Sep 26;283(39):26436-43. Epub 2008 Jul 3. PubMed PMID: 18599482; PubMed Central PMCID: PMC2546540.

Todi SV, Laco MN, Winborn BJ, Travis SM, Wen HM, Paulson HL. Cellular turnover of the polyglutamine disease protein ataxin-3 is regulated by its catalytic activity. J Biol Chem. 2007 Oct 5;282(40):29348-58. Epub 2007 Aug 10. PubMed PMID: 17693639.

Abstracts:

Winborn, B.J., Travis, S.M., Todi, S.V., Xu, P. Peng, J., Cohen, R.E. and Paulson, H.L. The deubiquitinating enzyme ataxin-3 edits K63-linkages in mixed linkage ubiquitin chains. Platform presentation and poster at American Society of Biochemistry and Molecular Biology Annual Meeting, San Diego, CA, April 5-9 2008

Todi, S.V., Winborn, B.J., Williams, A.J., and Paulson, H.L. Ubiquitination of the polyglutamine disease protein ataxin 3 enhances its activity as a deubiquitinating enzyme. Poster at American Society for Biochemistry and Molecular Biology Annual Meeting, San Diego, CA, April 5-9 2008.

Winborn, B.J., Travis, S.M., Todi, S.V., Xu, P. Peng, J., Cohen, R.E. and Paulson, H.L. The deubiquitinating enzyme ataxin-3 edits K63-linkages in mixed linkage ubiquitin chains. Platform presentation and poster at Graduate Student Symposium at St. Jude Children’s Hospital, Memphis, TN, March 25-29 2008

Winborn, B.J., Travis, S.M., Todi, S.V., Cohen, R.E. and Paulson, H.L. Ubiquitin chain editing by the neurodegenerative disease protein Ataxin-3. Platform presentation at Midwest Stress Response at Northwestern University, Evanston, IL, January 19, 2008

Winborn, B.J., Travis, S.M., Todi, S.V., Cohen, R.E. and Paulson, H.L. Ataxin-3, a polyglutamine disease protein, edits K63-linked and mixed linkage ubiquitin chains. Platform presentation at The Ubiquitin Family meeting at Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, April 25-29 2007

Winborn, B.J., Travis, S.M., Todi, S.V. and Paulson, H.L. Ataxin-3, a polyglutamine disease protein, has K63-linked ubiquitin editing activity. Poster at Carver College of Medicine Research Week, April 2007

Travis, S.M., Winborn, B.J., Paulson, H.L. Ataxin-3, a deubiquitinating enzyme with tandem UIMs: interactions with K48- and K63-linked polyUb chains. Poster at Keystone Symposium on Ubiquitin and Signaling, Big Sky, MT, February 2007

Winborn, B.J., Travis, S.M., Todi, S.V. and Paulson, H.L. Ataxin-3, a polyglutamine disease protein, has K63-linked ubiquitin editing activity. Poster at American Society for Cell Biology Annual Meeting, San Diego, CA, December 2006

Todi, S.V., Winborn, B.J., and Paulson, H.L. The ubiquitin chain-type specific protease ataxin-3 auto-regulates its own levels and affects the stability of other proteins in cells. Platform presentation at Society for Neuroscience Annual Meeting, October 2006



Honors and Awards

  • April 2007, Outstanding Poster Presentation, Carver College of Medicine Research Week