KUMC L. Yarbrough Research

Research Interests of L. Yarbrough

Microtubules are protein structures found in all eukaryotic cells. They are involved in many aspects of cell structure and function including segregation of the chromosomes at mitosis, maintenance of normal cell structure, motility, and cell transport. Microtubules are composed primarily of two genetically related proteins of about 50 kDa termed alpha and beta tubulin which form the protomer, an alpha-beta dimer. To better understand structure/function relationships we have developed systems for expression of recombinant alpha and beta tubulins. We are defining the mechanisms involved in formation of the tubulin dimer and how chaperones participate in this process. A colleague, Mark Fisher (link to Mark), who has extensive experience with chaperonins is participating in these studies. The methods used include molecular biology, expression of cloned genes, and analysis of protein structure and function by physical techniques such as circular dichroism, fluorescence, and absorption spectroscopy.

Another area of research involves molecular biology studies of the phosphatidylinositol (PtdIns) transfer proteins . These are small, approximately 32 kDa proteins which bind PtdIns and are involved in cell signaling and secretion. We have cloned and sequenced cDNAs encoding both the human and rat proteins and find that the amino acid sequence is extremely conserved, even more so than tubulins. We are using molecular genetic and biophysical approaches to define structure/function relationships in the protein. The cloned genes have been expressed to high levels in bacteria and physical studies of protein structure are now underway. (link to gmh)

A third area involves studies of cardiac responses to stress and aging. A number of studies in our lab and others have shown that stress can produce changes in the heart which are similar to those found during aging. Using a rat model system we have been defining the change in gene expression which occurs during stress or aging. Many of the heat shock proteins have been found to be chaperones, proteins which interact with other proteins during folding and/or assembly. We are examining the expression of a number of heat shock proteins such as HSP70, HSC70, HSP60, and ubiquitin in response to cardiac stress and aging. We hope to determine whether observed structural changes in the heart are associated with altered protein folding or degradation.