Elaine Lim, PhD, is an assistant professor of Genomics & Computational Biology at UMass Chan Medical School. Her research focuses on developing genomic methods for driving precision medicine in neurological diseases, with a recent emphasis on viral infections in neurodegenerative diseases. She has been a Psomagen customer for many years, since before we branched off from our parent company, Macrogen.
We were delighted to sit down with her for a discussion ahead of Science Appreciation Day 2024. Take a look at the rest of the article for a dive into her research background, the implications of her neurodegenerative disease findings, and her thoughts for people interested in beginning a scientific career.
From Autism to Alzheimer’s Disease
Dr. Lim's initial research focused on identifying and understanding the genetics of autism spectrum disorders (ASD). “I was drawn into autism because I care about understanding social behavior in children,” said Dr. Lim. Her research publications included using bulk and single-cell RNA sequencing to investigate genetic drivers of ASD using human brain organoids. Additional research included the identification of postzygotic mosaic mutations (PZMs) in nearly 6,000 ASD trios and crucial information about these mutations’ frequency and distribution.
Toward the end of her postdoctoral training with Dr. George Church at Harvard Medical School, Dr. Lim received an exciting funding opportunity that changed the focus of her research. “Six years ago I was funded by a National Institute of Aging (NIA) grant that is a component of the Accelerating Medicines Partnership Program for Alzheimer's Disease (AMP-AD). AMP AD is a public-private partnership that brings together academic and industry scientists and operates under open science principles — and I’m very grateful to participate in this large-scale collaboration.”
Working with her collaborators Dr. Benjamin Readhead at Arizona State University and Dr. Rigel Chan at UMass Chan Medical School, Dr. Lim sought to develop and use high-throughput human in-vitro systems to understand neuroinflammation in Alzheimer’s disease (AD) due to common pathogens such as viruses. For her, this project required a shift from studying ASD to AD and beginning this research was an uphill climb. However, AMP-AD is very well-organized and has regular progress report meetings, several working group meetings and multi-consortia meetings. Dr. Lim was able to learn from the exciting cutting-edge results presented by numerous established AD researchers. “Our project began with methods and systems development. There were definitely lots of questions, ‘How do we do this? What works, what doesn’t work?’ and sort of just trying and failing and trying again.”
Prior research has shown that viral infections are correlated with an increase in a person’s risk of developing neurodegenerative diseases, including AD. However, causality of viruses in the development or progression of neurodegenerative disease remains debated. “Unfortunately,” said Dr. Lim, “it’s not easy to test [long-term consequences of viruses in the brain] on actual people or animal models in a short amount of time. So we use lab-based processes, such as growing human brain organoids and directly infecting them with viruses.”
Their first major breakthrough came with the development of a high-throughput screening platform using these human-derived, lab-grown brain organoids. This platform can test the molecular and cellular impact of viral infections on human brain cells. As Dr. Lim explained, “Initially, we infected brain organoid cells from a single person with herpes simplex virus 1 (HSV-1) and influenza A, and found that HSV-1 affected a lot of genes that were preferentially enriched for AD-associated genes, as well as several molecular signatures associated with AD. Now we are very keen to use our platform to screen for the effects of HSV-1 and other viruses on many different people’s brain organoids. We’ll like to understand, ‘are some people more susceptible, are some people more resilient?’ That can guide us towards biomarker and therapeutic development.” This technology is a powerful tool to help researchers identify “genetic variants in these people that can exacerbate or protect them against the effects of viruses in the brain.”
Bridging Research and Patient Intervention
With this NIA AMP-AD consortium came the opportunity to collaborate directly with other stakeholders involved in AD research. This has helped to bridge gaps between academic research, translational research, and patient care. In Dr. Lim’s opinion, this breadth of expertise is a major strength of the program.
When it comes to working with industry stakeholders, she said, “There are leadership representatives from pharmaceutical companies who are aware of our research findings from Day One, when we had nothing or a tiny set of results…. In some sense they help guide our research to be more informative for therapeutic development and eventually to help patients, so our research is not just about understanding something fundamental but will also have translational value beyond academia. I really appreciate that.”
She’s also seen a lot of value from working with “the viewpoint from non-academic people who have a vested interest in advancing therapeutics for AD. Part of that is also collaborating with the Alzheimer’s Association, which is one of the biggest advocacy groups for AD and other neurodegenerative diseases. They are also part of that NIA initiative so they would have the outreach to patients to explain what our results from our research findings mean to the layman.”
The Alzheimer’s research arm of AMP includes several other major stakeholders, including the NIA, FDA, FNIH, Eisai Inc., Gates Ventures, Takeda Pharmaceutical Company Limited, Alzheimer’s Association and GSK. Now in the second iteration of the AMP program, researchers are building upon past target discovery efforts with improved molecular characterization of AD in the brain.
Alzheimer’s Disease: Nearing the Finish Line
As research on Alzheimer’s disease comes closer to developing new therapeutics, Dr. Lim and her collaborators have experienced an increased sense of urgency in their work. As she said, “I feel like there’s a personal commitment as well to try to understand [Alzheimer’s disease], to try to work through therapeutics and early diagnoses. I am one of many researchers in the field. Collectively, everyone will advance the field.”
In her opinion, the work done by AMP-AD researchers and other researchers is nearing actionable results. “I think therapeutics for a lot of common neurodegenerative diseases are in sight within the next couple of years or so, so it’s really exciting.” As her team identifies compounds associated with viral infections in the brain, the question then becomes, how can those be combated?
Additional Applications: Understanding Long COVID
Dr. Lim’s research group began exploring viral impacts on neurodegenerative diseases before the pandemic. However, the implications of SARS-CoV-2 on neurodegenerative diseases is now an area of interest for her group. In 2022, nearly 7% of the adult US population had experienced long COVID, and over 3% were currently dealing with long COVID symptoms. Some studies report a prevalence as high as 14% in the US, with evidence that long COVID causes negative symptoms across multiple organ systems.
Recently in 2024, Dr. Lim and two other researchers (Dr. Rigel Chan and Dr. Fiachra Humphries) were awarded a grant to explore the impacts of long COVID on neurodegenerative diseases, thanks to generous support by the PolyBio Research Foundation. Using the same approach of infecting brain organoids with SARS-CoV-2, the team will search for molecular signatures of neurodegenerative diseases.
Inspiring the Future
For students and aspiring scientists, Dr. Lim’s advice is: “Go into a field that you may not know a lot about, but are excited about…. I think that when I was younger, I definitely felt a bit more shy. ‘Oh, but what if I’m not qualified, what if I can’t do this? It’s not exactly something that I’ve been doing.’ However, I will highly encourage everyone to take that leap and get into something that you’re excited about. And who cares if you know a lot or know very little about it, because I think that passion and enthusiasm can really drive and make a difference in a lot of things.”
Readers interested in Dr. Lim’s research can read their preprint detailing her lab’s brain organoid screening platform and initial results.
