Hirosha Geekiyanage
geekiyan(at)msu.edu
PI:
Christina Chan
Lab:
517-432-1003
Michigan State University
2125 Engineering Building
East Lansing, MI 48824
Hometown:
Colombo, Sri Lanka
Undergraduate Institution:
University of Colombo, Sri Lanka
Staffordshire University, UK
Project title:
The Role of Diet Induced Ceramide in the Progression of Alzheimer's Disease
Project Description:
Alzheimer's disease (AD) is the most common cause of dementia with over 100,000 deaths every year in the United States alone. With a worldwide afflicted population of 24 million, a number that is expected to increase to 100 million in 40 years, AD is a genetically complex, heterogeneous, progressive neurodegenerative disorder characterized by amyloid beta (A?) plaques and neurofibrillary tangles. The contribution of high dietary fat intake to the etiology of AD has been widely discussed. However, dietary contribution to the progression of AD still needs to be addressed. Increased levels of the sphingolipid ceramide, has been attributed to high dietary fat intake and to AD like pathology in cell culture. Therefore, it is hypothesized that high fat diet induced ceramide may play a role in the etiology/progression of Alzheimer's disease. In understanding the role of ceramide, understanding the regulation of Serine palmitoyltransferase (SPT), the primary enzyme responsible for the de novo synthesis of ceramide, is of significant importance. While researchers have studied SPT in context to its inhibition, the regulation of SPT still remains obscure. This research intends to address the post-transcriptional regulation of SPT through microRNAs (miRNA). While, understanding the effects of high fat diet on the progression of AD is the primary goal of this research, the specific aims include 1) understanding the regulation of SPT, 2) investigating the involvement of ceramide in the progression of AD with respect to diet and 3) understanding the relationship between the expression of miRNA and the progression of AD in relation to a high fat diet. The preliminary results suggested that 1) SPT is post-transcriptionally regulated through three miRNAs, 2) A? plaque load, hyperphosphorylation of Tau, neuronal cell death and ceramide levels increased with high fat diet, in a transgenic mouse model of AD and 3) the miRNAs involved in the regulation of SPT are down regulated in mice fed with a high fat diet. Finally, this research intends to suggest a potential drug target to regulate SPT in order to improve the progression of Alzheimer's disease.
Research Interests:
Alzheimer's disease, miRNA, somatic cell nuclear transfer (SCNT)