Research Interests:

Biotechmology and Protein Engineering

Cell and Tissue Engineering

Protein Folding

Neurodegenerative Diseases

Education:

Postdoctoral Research Associate (2005-2007), The Scripps Research Institute

Ph.D. in Chemical Engineering (2005), University of Texas at Austin

Laurea in Biotechnology (2000), University of Bologna, Italy

The flexibility of the polypeptide backbone, combined with the multitude of non-covalent interactions established by amino acid side chains, allows a protein to assume a variety of three-dimensional conformations. Failures of the folding mechanisms to assist in the formation of native protein conformations results in the accumulation of dysfunctional or unstable protein structures; trace amounts of aggregates may also occur spontaneously especially during aging. Therefore, a delicate balance between two main protective strategies –- the repair of damaged proteins and their selective degradation - has evolved in all organisms. Complex interactions among molecular effectors of the chaperone and degradation systems maintain this homeostatic equilibrium in eukaryotic cells.  These are commonly referred to as protein quality control processes (QC). QC is developed to assist the folding of newly synthesized proteins and refold or degrade polypeptides that fail to attain or maintain a native structure. Its proper function is crucial in preventing the deposition of aggregation-prone, misfolded polypeptides associated with degenerative disorders, such as Alzheimer's and Parkinson diseases.

The intra- or extracellular accumulation of aggregated proteins –- whose identity determines the specific clinical manifestations –- and the formation of highly ordered fibrils have recurrently been associated to neurodegeneration and amyloid diseases. The molecular determinants that cause a protein state to be predisposed to aggregation have not been completely determined. However, evidence exists for an underlying link between impairment of protein folding and the formation of dysfunctional, aggregation prone proteins. In physiologic conditions, such cellular malfunctions are rescued by protective cellular systems, namely chaperones and degradation systems. It is therefore proposed that mutations that cause accumulation of misfolded proteins, or age related collapse of QC, alter the delicate balance between the cellular chaperones and the degradation systems.

My research interests focus on the relationship between protein folding and disease, the molecular determinants of cellular protein folding, and on the development of protein engineering strategies to enhance cellular chaperone and/or degradation systems.  Our goals are to obtain a broader understanding of the molecular mechanisms involved in cellular protein folding, and to develop methods for manipulating eukaryotic cells, which can be used for therapeutic applications.

CHEMICAL & BIOMOLECULAR ENGINEERING DEPT. MS-362
Rice University PO Box 1892 Houston, Texas 77251-1892	E-mail: chbe@rice.edu	Phone: (713) 348-4902 FAX:(713) 348-5478