Dr. Paola C. Rosas
TAMHSC Graduate student
Phone: 254-743-1215
Fax: 254-743-0247
Email: prosas@medicine.tamhsc.edu

Education
1995 - Pharmacy and Biochemistry from Universidad Catolica Santa Maria, Peru
2000 - M.D. (equivalent) from Universidad Nacional de San Agustin, Peru

Summary of Research Interests
My project is focused on understanding the role of heat shock proteins in type 2 diabetes mellitus (T2DM). More than 220 million people worldwide have diabetes and T2DM comprises 90% of people with diabetes around the world. Despite dramatic advances in the generation of new drugs to treat insulin deficiency and insulin resistance; there remain a big gap in preventing and halting β-cell mass deficiency as a result of misfolded islet amyloid polypeptide hormone (amylin) which forms toxic aggregates that destroy pancreatic β-cells. Our primary goal is to explore the mechanisms of amylin toxicity and design new strategies of treatment using heat shock proteins as molecular chaperones.

It has been previously demonstrated that amylin oligomers are more toxic to pancreatic β-cells and precede the deposition of islet amyloid that is present at autopsy in 96% of patients with T2DM. The presence of hydrophobic residues increases the susceptibility of amylin to aggregation when unfolded or partially folded. We investigate the role of heat shock proteins (HSP), especially important are seventy- and ninety-kilo Dalton heat shock protein (Hsp72) and (Hsp90), respectively, in chaperoning amylin and preventing its toxic aggregation.

We have demonstrated that thermal stress significantly upregulates the expression of Hsp72 and Hsp90 in pancreatic β-cells and therefore prevents proteotoxicity due to amylin oligomerization by 10 to 25%. Taken together, these studies suggest that harnessing the heat shock response to offset the detrimental effects of amylin deposition and to prevent β-cell death is a worthwhile approach in the management of T2DM. To explore how amylin causes intracellular toxicity, we are generating a transgenic Caenorhabditis elegans that will express human amylin in different systems. We will evaluate the outcomes and phenotypes and will demonstrate the role of heat shock proteins in attenuating and/or preventing the toxic oligomerization of amylin.

Collaborations
We are currently generating the human amylin transgenic C. elegans model in collaboration with Dr. L.R. Garcia from the Department of Molecular and Cellular Medicine, Texas A&M.