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Research Projects

Centrin

Post-translational modification and calcium binding are key pre-requisites for centrosome duplication and separation. These processes are regulated in healthy tissues and are defective in disease states such as cancer. Abnormalities, such as amplified and multiple centrosomes, are often observed in human breast, colorectal, and other cancers.

Centrin is an EF-hand protein that plays both structural and regulatory roles in the centrosome. This calcium-binding protein interacts at low calcium levels with a novel 1242-amino acid protein known as Sfi1, which contains up to 23 centrin-binding sites. Coupled biophysical, structural, and dynamic analyses of the centrin/Sfi1 complex are essential to the understanding of its biological function

EGFR

The goal of this research project is to elucidate the role of a soluble isoform of epidermal growth factor receptor (110 kD-sEGFR), a serum biomarker for epithelial ovarian cancer, in modulating the interaction of epidermal growth factor (EGF), and transforming growth factor receptor (EGFR). Dimerization of epidermal growth factor receptor (EGFR) upon ligand binding is considered the key event that leads to receptor activation. We propose to define the protein-protein interactions of 110 kD-sEGFR, a naturally ocurring protein. This protein is generated by alternative splicing of the EGFR message. 110 kD-sEGFR is comprised of four subdomains of the extracellular domain of EGFR, contains 78 additional carboxy-terminal amino acids, and it is a putative GPI-anchored protein. We are also interested in performing a comparative analysis amongst the known EGFR ligands and EGFR with 110 kD-sEGFR by FT-IR spectroscopy.

Lung Surfactant

Replacement surfactant therapy containing phospholipids and 1% weight hydrophobic surfactant proteins (SP-B and SP-C) from animal source has been proven clinically to stabilize patients with respiratory distress syndrome (RDS) due to its ability to spread rapidly and lower surface tension to near zero values at rates required to prevent lung collapse. A new generation of synthetic lung surfactant is being developed based on peptide analogs and peptoids of SP-B and SP-C to address the cost of the treatment. For the effective design of this new synthetic surfactant a detailed study must be carried-out, to address, three essential properties whose mechanism is not well understood for these surfactants. First, the squeeze-out of unsaturated or unordered structures to prevent lung collapse. Secondly, re-uptake essential for stabilizing the lung after expiration (squeeze-out). Thirdly, is the role of the hydrophobic protein SP-C during squeeze-out and re-uptake. These experiments would naturally be followed by the evaluation of several synthetic peptides and peptoid mimics proposed for the design of the synthetic surfactant. The synthetic peptides and peptoids must have similar properties to that of SP-C found to be essential in natural exogenous surfactant preparations.

This interdisciplinary approach towards the study of this vital substance will provide a molecular level understanding of the dynamics that occur at or near the A/W interface and explore several synthetic peptides that may be used for the design of a new exogenous surfactant.