Welcome to the Flowers Lab
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Working towards healthy aging by detecting and treating Alzheimer’s disease at the very early stages.
One of the main focuses of the Flowers lab is understanding the impact of the glycoprotein, APOE, on the early pathogenesis of Alzheimer’s disease (AD) and using this knowledge for the effective diagnosis and treatment of AD. We use human induced pluripotent cells (iPSCs) and advanced technologies including mass spectrometric (MS) and functional metabolism techniques to better understand the changes that occur between the different APOE genotypes as well as in AD.
Understanding APOE, the whole molecule
APOE is the most significant genetic risk factor for sporadic Alzheimer’s disease with the APOE4 genotype increasing risk, the APOE2 genotype reducing risk and APOE3 considered neutral risk. The Flowers lab are working to understand APOE as a whole molecule including its attached modifications. APOE has sugars attached, O-glycosylation, and it is critical to understand these large modifications and how this impacts its function. Most significantly we need to know how these modifications change over time with healthy aging and in AD. We are investigating how these changes may relate to AD pathogenesis (the very early processes that cause the onset of AD) and how they change with AD progression.
By understanding what starts the brain on the path toward Alzheimer’s disease we can stop progression to AD
Our work is critical because we can put it into ACTION. By detecting changes in the blood very early in the disease process, well before there are any symptoms, we have a greater chance of treatment success. This is important as it becomes more and more clear that treating AD as early as possible in the disease process may be essential for stopping it.
Investigating metabolism changes in Alzheimer’s disease.
It has long been known that Alzheimer’s disease sufferers have defects in brain glucose metabolism, and it is likely that APOE may play a role in these deficiencies. The Flowers lab is working to understand this important intersection and how these metabolism changes may be a critical target for intervention. We are also investigating how this alters carbohydrate post-translational modifications including glycosylation and advanced glycation end products.
The right tools for the job
We use a range of advanced techniques to answer these difficult questions. To understand glycosylation and other protein changes and modifications, such as advanced glycation end products, we use mass spectrometry. This is a precise and flexible tool that allows us to understand these sugars in detail as well as allowing quantification. To understand disease and the associated changes we use human induced pluripotent stem cells. These are cells taken from adults that are then reverted back to the stem state. These stem cells can then be differentiated into a range of different cell types which allows us to really understand how they contribute to the disease processes of AD. We use CRISPR/Cas9 to edit the genome of these cells to allow us to more accurately investigate the impact of APOE genotype on these AD disease processes.
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