Christina Coughlan

Assistant Professor, Department of Biological Sciences

Research Interests:

Alzheimer’s disease and Dementia in Diabetes

Alzheimer’s disease (AD) is a neurodegenerative disorder that leads to memory loss and death of all patients affected. Only 5% of AD cases are genetic leaving 95% of AD cases as having no fully understood cause (sporadic). Regardless of the origin, genetic or sporadic, all patients with AD have an increased production of amyloidogenic fragments in their brains. These fragments are formed from a protein known as Amyloid Precursor Protein (APP).

APP is a protein that is found in every cell in our body. Although its function as a full-length protein is poorly understood, we do know that fragments of APP play a central role in the development of AD. Abeta is a peptide fragment derived from APP that has many toxic functions any or all of which may lead to the death of brain cells that cause AD. Given the toxic role of this peptide much research has focused on trying to understand why and how Abeta peptide reaches such high levels in our cells and in our brains. We hypothesize that the removal of the activity of a hormone known as leptin is one of the factors that is to blame. Another is the loss of cell functions that normally remove toxic proteins and protect cells.

Leptin is a hormone released from fatty tissue which is involved in suppressing appetite and in modulating fat deposition and brain and nerve cell development. In the absence of leptin Abeta peptide deposition is favored and so more toxic peptide is found in brain cells. Interestingly, aging and obesity are risk factors for the development of AD and insensitivity to leptin is known to develop as we age or become obese. Thus by either aging or becoming obese, the effects of leptin are removed and the risk of AD increases. We hypothesize that these connections are more than just coincidence. We are thus interested in understanding the effect(s) of leptin deficiency and how it acts as a risk factor for the development of AD. We are also working on projects to help us understand the parts of the cell that are important for generating Abeta peptide and, in collaboration with Dr. Shaheen, designing therapeutic approaches to remove this toxic peptide once it is made.

• Spavero, L.J., Patz, S., Brodsky, J.L., and Coughlan, C.M. (2007) Proteomic analysis of the Amyloid Precursor Protein fragment C99: Expression in Yeast. Anal. Biochem. 370:162-170 (DOI: 10.1016/j.ab.2007.07.033)
• Coughlan, C.M., and Brodsky, J.L. (2005). Use of yeast as a model system to investigate protein conformational diseases. Mol. Biotechnol. 30(2):171-180. (invited publication) (DOI: 10.1385/MB:30:2:171)
• Coughlan, C.M, Walker, J., Cochran, J., Wittrup, D. and Brodsky, J.L. (2004) Degradation of mutated bovine pancreatic trypsin inhibitor (BPTI) in the yeast vacuole suggests post endoplasmic reticulum protein quality control. J. Biol. Chem. 279(15):15289-15297 (DOI: 10.1074/jbc.M309673200)
• Coughlan, C.M and Brodsky, J.L (2003) The use of yeast as a model system to investigate protein conformational diseases. Methods in Molecular Biol. 232:77-90
• Chalasani. S.H., Baribaud. F., Coughlan. C.M., Lee. V.M.Y., Doms, R.W. and Raper. J.A. (2003( The chemokine SDF promotes the survival of embryonic retinal ganglion cells. J. Neurosci. 23(11):4601-4612
• Puffer, B.A., Sharron, M.P., Coughlan, C.M., Baribaud, F., McManus, C.M., Lee. B., David. J., Price. K., Horuk, R., Tsang, M., and Doms, R.W. (2000). Expression and coreceptor function of APJ for primate immunodeficiency viruses. Virology 276(2):435-444 (DOI: 10.1006/viro.2000.0557)