Postdoc Highlight: Kirstan Gimse – Combining computation and gene therapy for Alzheimer’s treatments

By Leo Barolo

Spending most of her life in the Midwest, Dr. Kirstan Gimse received her bachelor’s degree from UW-Parkside. She later completed her PhD in Cellular and Molecular Pathology at UW-Madison, investigating gene therapy approaches to the treatment of neurodegenerative disorders.

Dr. Gimse has taken her passion for investigating neurodegenerative diseases and pushed it into a new area by working as a Genomic Sciences Training Program (GSTP) Postdoctoral trainee with Drs. Sushmita Roy and Krishanu Saha. Her work is investigating the molecular mechanisms driving pathology in Alzheimer’s Disease (AD) in a way that incorporates a significant amount of computational analysis, including gene regulatory network inference.  By combining genomics, computational biology, and gene therapy, Dr. Gimse hopes to advance gene-therapy-based therapeutics for the disease.

Dr. Kirstan Gimse

Please give us an overview of your research project(s).

The etiology (cause) of sporadic AD is still very poorly understood. There are a number of genetic and environmental factors that we know increase the risk of developing this disease, but it’s still not clear how the scales are tipped toward pathogenesis. Even the role of amyloid plaques, one of the primary characteristics of AD, isn’t entirely clear, as many individuals who develop these plaques never show any symptoms of AD, and plaque-clearing therapeutics have shown little efficacy in AD treatment. So, if we are able to identify regulators involved in shifting cells from healthy or intermediate disease states toward the dysregulation we see in disease, we may be able to identify novel targets for therapeutic intervention.

My research has two primary goals: The first is to characterize the impact of a potentially therapeutic CRISPR/Cas9 gene edit for AD on gene expression and regulatory network organization, and the second is to use this data to better understand the molecular mechanisms of pathogenesis in sporadic AD.

This project relies heavily on computational analyses. I’m using network inference algorithms, network rewiring analyses, and multitask learning to identify cell-type specific gene regulatory networks, understand how these networks change with disease and with gene editing, and to jointly identify networks across multiple cell types. This is an entirely new area for me; before I joined the GSTP, I had very little experience with computational analyses. I’m really excited about the opportunity this program has provided to expand my skills and knowledge into this new area, which I believe will be key to precision medicine and unraveling disease etiology.

What is the single person, event, or experience that most influenced your trajectory to where you are today? 

I don’t think it would be possible to identify a single person or event that influenced my trajectory. As a child, I had multiple teachers, as well as my older brother, who sparked a fire of curiosity in me. My mom used to give us math workbooks and logic puzzles as rewards for good behavior, which I’m sure contributed to my love of learning, and I have been so lucky to have had several amazing mentors throughout my undergrad, grad, and postdoctoral careers that have been instrumental to my success. But even outside these traditionally influential roles, many individuals have encouraged me and helped me find my path, including friends, co-workers, and even a customer in a restaurant where I worked.

What are some of your interests outside research?

I am somewhat obsessed with the Great Lakes. It’s a goal of mine to swim in each of them; I’ve got Michigan and Superior so far. I’m really just a big fan of fresh bodies of water in general — lakes, rivers, waterfalls — but I could swim out to the middle of Lake Michigan and just float there all day. It’s my favorite place to be.

What advice would you give a young person interested in graduate school or research? 

I would say follow your passion, be ready to work hard and fight for what you want in life, but at the same time, it’s important to keep an identity outside of your research and grad school. It’s important to have hobbies and purpose outside of grad school and to keep those even when the pressures of research might want to take over. Inevitably, things will fail in your research- that’s just the nature of the job. When working on a graduate degree, it can be easy to make your research your whole identity, and when things fail, it can feel very personal – as if you yourself have failed. It’s important to remember that failure is part of the process and that you’re a whole person outside of the lab- you are not your experiments.

 

Dr. Gimse is still considering her next steps but is particularly interested in translational research and teaching.