Education

B.S., Industrial Biotechnology, University of Puerto Rico, Mayagüez, P.R., 2000
Ph.D., Biochemistry and Molecular Biology, Mayo Graduate School, Rochester, MN, 2008
2nd year FIRST Postdoctoral Fellow, 2008 - present

Research Statement

I work with a yeast protein of unknown cellular function called Pin3 (protein that induces the appearance of prion when over-expressed). Prions are proteins that induce various neurodegenerative diseases. These proteins are prone to aggregation, are considered infectious agents and they can be passed on to cellular offspring. Diseases in humans that are related to protein aggregation include Mad Cow disease, Parkinson’s disease, Huntington’s disease, and Alzheimer’s disease among several others. The yeast Saccharomyces cerevisiae contains several prion and prion-inducing proteins. Therefore, we can use yeast as a model system to facilitate the characterization of proteins involved in prion formation, processing and degradation.

The cellular role of the yeast protein Pin3 is not well understood. However, we know some details of its behavior. For example, overproduction of Pin3 induces the formation of the [Psi+] prion, it binds a key protein in the formation of the actin cytoskeleton, and it binds ubiquitin. Pin3 has an N-terminal SH3 domain, a C-terminal polyglutamine rich region (polyQ) and it is ubiquitinated.

The link between prion-inducing proteins and the ubiquitin proteasome system (UPS) is not well defined. The ubiquitin proteasome system is a major “recycling center” for cellular proteins. I believe that Pin3 is a good candidate to study if there is a link between prion-inducing proteins and the UPS. Further, I want to determine a mechanism of degradation for Pin3, and understand the relevance of ubiquitin binding. 

Publications

Moffatt, N.S., Bruinsma, E., Uhl, C., Obermann, W.M., Toft, D. (2008) Role of the cochaperone Tpr2 in Hsp90 chaperoning. Biochemistry. 47(31):8203-13

*Cintron, N.S., Toft, D. (2006) Defining the requirements for Hsp40 and Hsp70 in the Hsp90 chaperoning pathway. J Biol Chem.  281:26235-44.

Bennett, P.V., *Cintron, N.S., Gros, L., Laval, J., Sutherland, B.M. (2004) Are endogenous clustered DNA damages induced in human cells? Free RadicBiol Med.  37:488-99.

Sutherland, B.M., Bennett, P.V., *Cintron, N.S., Guida, P., Laval, J. (2003) Low levels of endogenous oxidative damage cluster levels in unirradiated viral and human DNAs. Free RadicBiol Med. 35:495-503.

Sutherland, B.M., Bennett, P.V., *Cintron-Torres, N., Hada, M., Trunk, J., Monteleone, D. (2002) Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation. J Radiat Res (Tokyo). 43 Suppl:S149-52.

* Maiden name

Emory University School of Medicine
Department of Biochemistry
Rollins Research Center, Room 4070
Atlanta, GA 30322
Tel: 404.727.0412
Email: nmoffat@emory.edu