Development of a New Model of Brain Vasculature in the Test Tube

Jerome Robert, PhD
University of British Columbia (Vancouver, British Columbia, Canada)

Mentors

Cheryl Wellington, BSc, PhD
University of British Columbia (British Columbia, Canada)
Year Awarded:
2015
Grant Duration:
January 1, 2016 to December 31, 2018
Disease:
Alzheimer's Disease
Award Amount:
$100,000
Grant Reference ID:
A2015324F
Award Type:
Postdoctoral Fellowship
Award Region:
International
Jerome Robert, PhD

Development of a Novel Tissue Engineered Model of the Cerebrovasculature

Summary

With every heartbeat, one quarter of all the blood in the body flows through the brain, and this activity is essential to keep neurons in the brain healthy throughout life. Scientists have long understood that keeping blood vessels in the brain healthy may offer new ways to treat brain disorders, including Alzheimer’s disease (AD). A big challenge, however, is that there are not many methods to study the brain’s blood vessels outside of an animal model, and animals models may not always mimic the human condition closely enough to provide answers that help to develop effective treatments for dementia. We have made considerable progress in being able to grow functional three dimensional human-derived blood vessels in the test tube using “tissue engineering” technology, and are now focused on adapting this technology to make brain blood vessels that mimic those in the human brain. Our technologies will be used to rapidly test several questions about how these vessels become damaged in AD and how to prevent or repair this damage.

Details

We are developing novel methods to analyze in the test tube the importance of the brain vessels in the development of AD.

Our first aim is to develop a model of the large blood brain vessels using different types of cells, namely astrocytes, smooth muscle and endothelial cells, in a process known as tissue engineering. Alzheimer's patients suffer from aggregated forms of amyloid beta protein (Aβ) within the brain, as well as in their brain vessels. In order to mimic this pathology, we will inject Aβ within our engineered vessel and analyze the function of the tissues. In the second aim we are developing a model of small blood vessels in the brain, named capillaries. To do this, we are using special cell culture devices (microfluidic chips) enabling the cell to growth in three-dimensional organization mimicking capillaries. Same as with the first aim, we plan to further analyze the effects of Aβ on these structures.

Numerous scientists have agreed that we need a better understanding the role of the brain vessels in the pathology of AD, and in recent years that’s been emphasized as a priority topic. However a critical roadblock to progress in this topic is the lack of appropriate models. Our proposal is a direct answer to this roadblock and is therefore particularly innovative. Our research will permit to better understand the role of the brain vessels in AD and therefore to develop specific treatments. 

About the Researcher

After completing a bachelor’s degree in general biology and a master’s degree in functional biology at the University of Neuchâtel (Switzerland), in 2009, I joined the Integrative molecular Medicine (ImMED) program at the University of Zurich (Switzerland) for my PhD studies.  My PhD training focused on the role of interleukins to regulate high-density lipoprotein (HDL, "good cholesterol") and its major protein (apoA-I) binding and transport through endothelial cells. In addition, I developed a tissue-engineered artery equivalent with which to investigate low-density lipoprotein (LDL, "bad cholesterol") uptake and the initiation of atherosclerosis. In September 2013, I joined the laboratory of Cheryl Wellington, PhD, at the University of British Columbia (Canada) as a postdoctoral fellow, where we use tissue engineering techniques to build a physiologically relevant model of the cerebrovasculature. 



"Since childhood, I have taken a strong interest in all living things in the world surrounding me, and it was a natural choice to study biology to better understand them. Over the years I specialized in human vascular biology, and I recently joined a group at the University of British Columbia to investigate the influence of the brain vasculature on the development of Alzheimer's disease.

Over the years of my so-far short scientific career, I have realized that in addition to great ideas, funding is one of, if not the, most important part of the research. With the help of generous donors, foundations such as BrightFocus help make research possible. Through their grants, especially those that go to support postdoctoral fellows, they advance the personal scientific careers of individuals, helping them to develop and flourish, and they also promote the exchange of ideas between universities.

Being awarded this BrightFocus grant represents a unique opportunity for me, and a chance to achieve my personal goal of becoming an independent researcher. I would like to warmly thank the BrightFocus Foundation, as well as all the anonymous donors, that made this funding possible."

Publications

Button EB, Gilmour M, Cheema HK, Martin EM, Agbay A, Robert J, Wellington CL. Vasoprotective Functions of High-Density Lipoproteins Relevant to Alzheimer's Disease Are Partially Conserved in Apolipoprotein B-Depleted Plasma. Int J Mol Sci. 2019 Jan 22;20(3). pii: E462. doi: 10.3390/ijms20030462. PubMed PMID: 30678190. PubMed Icon Google Scholar Icon

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