Investigating the Neuroscience of Aging

Rogan Grant is a Schmidt Science Fellow and Kimberly Querrey Fellow at Feinberg studying the intersection of mitochondrial dysfunction and neuroinflammation.

After completing his PhD in neuroscience as part of the Northwestern University Interdepartmental Neuroscience (NUIN) program, Grant signed on to stay at Northwestern, continuing his research in the laboratory of Navdeep Chandel, PhD, the David W. Cugell, MD, Professor of Medicine in the Division of Pulmonary and Critical Care.

Where is your hometown?

I was originally born in Crested Butte, CO (tiny, very beautiful ski town near Aspen), but I unfortunately can’t say I remember much of it. My hometown would more realistically be Pittsburgh, PA, where I spent most of my formative years.

What led you to Northwestern?

I originally came to Northwestern to pursue my PhD in 2017 in the NUIN program in the laboratory of Scott Budinger and Alexander Misharin. There, I studied the molecular and cellular mechanisms driving prolonged illness in COVID-19, relative to other severe pneumonias, as well as the potential impact of severe infection on the brain and cognition. Notably, elderly patients who develop pneumonia are at a substantially increased risk of long-term cognitive impairment, but very little is known as to why this is the case. In my postdoc, I therefore wanted to study how aging leads to inflammation in the brain. With support from the Kimberly Querrey Fellowship and Schmidt Science Fellowship, I was able to make a pivot from pulmonary biology to the neuroscience of aging in the laboratory of Navdeep S. Chandel.

What are you currently working on?

I apply data science approaches to “high content” techniques such as bulk, single-cell, and imaging spatial transcriptomics and metabolomics, as well as targeted, more causal methods, such as genetic perturbation. My goal is to better understand the mechanisms necessary and sufficient to drive age-related neuroinflammation. By profiling the brains of aging mice, as well as postmortem human brains in collaboration with the Mesulam Institute for Cognitive Neurology and Alzheimer's Disease here at Northwestern, we have found that microglia - a key immune cell in the brain - become increasingly inflamed in old age. Notably, this immune activation occurs without any known infection. We are currently exploring a hypothesis where these cells mistake their own DNA for a viral infection and mount an aberrant immune response that may damage the brain. Additionally, we are studying how changes to metabolism in these cells can alter their inflammatory activation through genome-scale CRISPR screens, as well as targeted perturbations to key metabolic pathways in mice.

How does your work support the research enterprise at Feinberg?

My work is increasingly intersectional, bringing together neuroscience, immunology, metabolism, and pulmonary biology across multiple departments and divisions. This work helps to support the vision of the Simpson Querrey Lung Institute for Translational Science (SQLIFTS), which aims to support collaboration across disciplines for the benefit of human health. My hope is that developing a better understanding of how “sterile” inflammation originates in the aging brain can lead us to better understand how severe illness can lead to lasting cognitive impairment. In the much longer term, I hope that this can inform the development of therapeutics to slow or even reverse these maladaptive processes.

Why do you enjoy working at Northwestern?

I love working at Northwestern because of the strong focus on the causal mechanisms driving neurodegenerative disease, as well as the culture of cross-discipline collaboration that benefits researchers with broad interests like me. I also appreciate Northwestern’s strong commitment to supporting trainees at each stage of their careers, which has immensely benefitted me and countless others. There’s also something to be said for being able to perform this research in a city as beautiful, culturally rich, and affordable as Chicago, which makes the experience here all the more enjoyable!