Ann W. Nguyen, PhD
Jack, Joseph & Morton Mandel School of Applied Sciences
Case Western Reserve University
Tell us about yourself and how you are involved with the Cleveland Alzheimer’s Disease Research Center (CADRC).
In 2021, I joined the faculty at Case Western Reserve University as an Assistant Professor. Having trained as an immunologist, I have long been fascinated by the ability of the immune system to protect our bodies from an array of never-before-seen insults and at the same time promoting tissue integrity and orchestrating wound healing. As a pre-doctoral student, I studied a microbial sensing pathway that acts in our gut to restrict the development of Crohn’s disease. I also found this microbial sensing pathway could be engaged in tissues distant from the gut to control the location and function of blood stem cells during periods of stress or infection. As a post-doctoral fellow, my interest in the nervous system blossomed and I became immersed in human and animal models of neurodegenerative disease such as Amyotrophic lateral sclerosis and Frontotemporal dementia. During that period, I made the surprising discovery that the gut microbiome promotes neural inflammation in mammals with the most common ALS genotype. Now I am leveraging funding from the CADRC to uncover which components of the gut microbiome tip the balance between a healthy brain and a brain engulfed by inflammation.
What are your main activities and goals as they relate to brain health?
One of the greatest mysteries in our society is why some people develop neurodegenerative diseases such as Alzheimer’s (AD) and others do not. It is clear that genetics play a role; we have identified genes whose mutation causes AD and other genetic variants that increase a person’s risk of the disease. However, most cases of AD cannot be linked to a single gene mutation suggesting that other aspects of our lifestyle such as diet, exercise, emotional wellbeing and microbial exposure play a role. Moreover, it is increasingly appreciated that inflammation happens within the brain during the early stages of AD. The main goal of my laboratory is to identify factors from our environment that affect immune cell support of neuronal health. My hope is that this knowledge will ultimately lead to new immunological and microbial therapeutic targets and help to direct people at risk of dementia towards clinical trials with the greatest chance of personal benefit.
What is the focus of your research currently, and where do you see your work going in the next two-five years?
My group is currently pursuing two interlocking approaches to understand how environmental factors affect immune cell support of brain health. In the first approach, we use cell and animal models to determine which bacteria within the gut can promote neural inflammation. The knowledge gained will inform strategies to reduce bad actors in our gut and to identify molecules produced by immune cells and bacteria that sensitize neurons to degeneration. In the second approach, we use the power of induced pluripotent stem cells to generate and study the neurons and glia that degenerate in disease. Human iPS derived cells enable us to ask how our genotype influences microglia to support neuronal function under inflammatory conditions and to explore cellular compartments that are engaged by diverse environmental risk factors. In the future, we will incorporate human gut microbiota from dementia and pre-dementia patients into our model systems to enable personalized screening of candidate therapies.
How do you see research in brain health/Alzheimer’s Disease/dementia evolving in the next 2-5 years?
Techniques to study gene expression at the single cell level have rapidly advanced and have already begun to transform our understanding of neurodegenerative diseases including AD and Multiple sclerosis. These studies have led to the discovery of conserved pathways that are engaged in response to neuronal degeneration—such as myelin metabolism—and have highlighted a fascinating level of molecular heterogeneity across neurodegenerative disorders and between individuals with the same diagnosis. I envision a future where we integrate omics data from our microbiome, immune system, nervous system and genome to classify patients into treatment groups at the earliest stages of neurodegenerative disease.
Do you have any suggestion or recommendations for students or young researchers who wish to get more involved in brain health research?
Start young, be open to new challenges and give it your all. Even if you have no prior experience, showing a faculty member that you have read about their research and are enthusiastic about learning more can be a great way to earn a position in their lab. In addition, do not be afraid to try something outside your comfort zone. Basic science research looks great on medical school applications and training in a clinical setting can give a unique perspective to explore brain biology on the bench.