Decoding Demyelination: A Look Inside Dr. Jeffrey Huang's Innovative Research on MS
- Naama Ben-Dor
- Oct 22
- 8 min read
Multiple Sclerosis (MS) is a chronic autoimmune disease that damages the nervous system. Patients can experience numerous symptoms, ranging from fatigue, impaired vision, and decreased motor coordination, to memory deficits and difficulties with bowel and bladder function. Despite being one of the most common autoimmune disorders in the world, with 2.9 million people estimated to suffer from the disease in 2023, there are currently no cures available for MS. Recent advances in the field, however, offer new hope for patients. One such example is the exciting work conducted by Dr. Jeffrey Huang, whose lab at Georgetown University holds a patent for a potential new MS drug. Based out of nation’s capital, Dr. Huang and his team at Georgetown University are targeting an amino acid transporter that they recently identified, with the goal of reducing disease severity for MS patients. In this exclusive interview, Dr. Huang shares the journey that led him to his breakthrough discovery, additional successes along the way, and the path that led him to his impactful research on MS.
Introduction
Dr. Jeffrey K. Huang is a Provost's Distinguished Associate Professor in the Department of Biology at Georgetown University. His lab investigates the mechanisms of remyelination—a crucial repair process in brain disorders like multiple sclerosis (MS). This work has made impactful contributions toward developing therapies for patients with neurodegenerative diseases. Having served on peer review panels for major funding agencies such as the National Institute of Health (NIH), the National MS Society, and the Congressionally Directed Medical Research Programs, Dr. Huang is a trusted and influential figure in the field of MS research.
Beyond his scientific and medical contributions, Dr. Huang’s story serves as a powerful example of how curiosity, dedication, and mentorship can guide an uncertain start towards an impactful and fulfilling career. In an interview with The Catalyst, he shares some of the pivotal moments that shaped his career trajectory, his lab’s exciting breakthroughs and discoveries, and his candid advice for students seeking a meaningful career in science.
Dr. Huang’s Research Evolution: Remyelination & Multiple Sclerosis
As one of the most common autoimmune diseases in the world, with no cures discovered to date, Multiple Sclerosis has been a subject of great interest in the scientific community for decades. While the initial pathological event driving MS progression involves the infiltration of immune cells into the brain and spinal cord, symptoms of the disease primarily result from a process called “demyelination,” in which immune cells destroy myelin, an important structure in the brain that coats neurons.
Myelin – Function
Similar to the insulation on an electrical wire, our brain relies on a special coating called myelin to transmit high-speed electrical signals from one neuron to the next. This structure is formed by a population of cells in the brain known as oligodendrocytes, which send out extensions of their membrane and wrap them around neurons, creating dozens of insulating layers. While brain activity is primarily mediated by neurons, which send electrical signals to one another in the form of ion currents, myelin plays a key role in the process. By preventing ions from leaking out along the neuronal membrane, this protective coating ensures smooth, lag-free conduction. Myelin enables the high-speed signaling that our brain requires to rapidly respond to information from our surroundings in real time.
Myelin – Formation
Myelin also provides physical protection for neurons which, in contrast to oligodendrocytes, are unable to regenerate. The brain contains a large reservoir of oligodendrocyte precursor cells, which remyelinate neurons in response to injury. In healthy brains, remyelination is important to re-establish normal signaling—but in certain pathological conditions, it fails over time. In MS, specifically, patients often experience cycles of demyelination and remyelination for several years. Eventually, however, they enter a progressive stage of the disease where this natural repair process fails.
Dr. Huang’s Research Journey: The Beginnings
When he began his PhD at Mount Sinai School of Medicine, Dr. Huang originally planned to study cancer biology. His interests took a sharp turn, however, while doing a rotation with Dr. David R. Colman, where he was first introduced to the beautiful spiral wrappings of myelin. When his mentor showed him an electron micrograph image of the structure, he was mesmerized.
“I was curious about how you get this beautiful structure without anyone turning it—it just forms in the brain. That's when science really hit me in the head… When I was in Dave's lab, I realized there were questions behind anything that you see, and that you could start asking questions and exploring the unknown – The challenge of not knowing the answer, but then developing a hypothesis and solving it, was exciting.”
Not only did that experience assure Dr. Huang that he wanted to pursue a career in academic research, it sparked his deep fascination in myelin that has shaped his studies ever since. Upon completion of his PhD, Dr. Huang joined a lab at the University of Cambridge to study the mechanisms of myelin regeneration, where he shifted toward translational research on demyelinating diseases such as MS.
“As an autoimmune process, you have to start learning and appreciating the complexity of the immune system… So our lab started to learn immunology, started to use immune demyelination models in mice as a way to get a bit closer to understanding disease pathology and pathogenesis in MS… I would say what sort of got us to where we are is, we found that there is this particular amino acid transporter that is involved in driving inflammation.”
A Pivotal Discovery
As he analyzed the lesion environment in MS—the localized areas of damage in the brain and spinal cord due to immune cell infiltration—Dr. Huang observed an upregulation of neutral amino acids in the region. As critical metabolites, amino acids are required for many aspects of cell growth.
In his studies on immunology, Dr. Huang had learned of dysregulated amino acid transporters in other pathological conditions that cause excessive activation of immune cells. Since neutral amino acids, like those he’d observed in MS lesions, require transporters for cellular uptake, Dr. Huang wondered if inhibiting certain transporters with a drug could effectively “starve” inflammatory cells and restore a healthy environment, suitable for remyelination.
“This led me to speculate–and this was purely speculation… I thought, ‘Why don't we get the drug [an inhibitor of the transporter] and add it to our model to see if it has an effect?’… And it turned out that by inhibiting this transporter, we were able to dampen inflammation and enhance repair.”
To further test their hypothesis, the Huang Lab genetically modified a mouse line to “knock out” its expression of the transporter. When compared to mice that did not undergo genetic modification, those lacking the transporter showed reduced inflammation during the remyelination process. Even more strikingly, the knock-out mice exhibited an accelerated repair process.
Having corroborated these findings through additional experiments, Dr. Huang and his team have shifted their focus to investigate this protein as a potential therapeutic target for MS. Their strong preclinical data, accumulated over several years of hard work, has led them to an exciting collaboration with a pharmaceutical company, and a patent for a potential drug for MS patients.
The Power of Questions: A Methodological Breakthrough
While the significance of the Huang Lab’s drug development work is apparent even to those unfamiliar with the field of MS research, their contributions to the study extend even further. One of the core impediments that Dr. Huang and his team faced when they began to investigate the lesion environment of MS, was an inability to identify the sites in intact tissues.
“When you create a focal lesion in the mouse spinal cord, or in the brain, you don't know where that lesion is unless you section the tissue. So I wanted to be able to identify it or be able to visualize it on an intact tissue using some sort of dye.”
A seemingly far-reaching goal, some lab members questioned whether it would really be possible to develop a new visualization strategy. “They were like, ‘you're just being crazy, as always,’” Dr. Huang said.
“But I had an undergrad… So this is why I love undergrads: They're willing to take chances because, they're not like, trying to get a PhD out of a project. So they could take risks, and they want to learn.”
With his undergraduate research assistant, David, on board, they researched numerous dyes to test on the lesions. One of the dyes they came across, called neutral red, had been used by other researchers to preferentially bind to highly acidic living cells, such as macrophages, which maintain a low pH due to their high lysosomal activity. “So I asked David to try this, and a few others,” Dr. Huang said.
Through trial and error, they discovered that by injecting the mice with the neutral red two hours before sacrificing them, they could visualize the lesions without sectioning and fixing them—a process that restricts the analyses they could perform on the tissue. Then Dr. Maryna Baydyuk, an Assistant Research Professor who just joined Dr. Huang’s lab, took the project further and began to characterize neutral red labeled lesions in mice.
“Once we sacrifice the mouse and take out the [spinal] cord, you can see this big red spot where we created that lesion… We can now dissect it out and then do single-cell RNA sequencing and mass spectrometry and proteomics on it… So this approach was a major, major finding in my lab that opened up so many doors because it allowed us to now characterize the lesion microenvironment and the molecular and cellular composition of lesions during remyelination.”
A Mindset for Discovery: The Freedom to Fail
Professor Huang’s professional journey attests not only to the rewarding success produced through hard work and dedication, but also to the power of curiosity and a growth mindset. By leaning into the wonder that first drew him to study myelin, and seeking out important questions to probe, Dr. Huang was able to direct his intellectual passions towards tangible, meaningful impact. His journey shows that embracing the unknown, learning from failure, and allowing oneself to be captivated by a question is not only part of the process of science, but a fundamental component.
“When you're doing research, you can learn from your mistakes. That's how you get better. You have to not be afraid to do things. You have to just be ready to fail. And I say this, that for anyone who joins my lab. I always say, you're gonna fail, and you have to be okay with it. You have to mentally prepare for that… Because you're gonna do it and you'll repeat your experiments and troubleshoot several times before it works out. But that's okay as long as you're willing to keep doing it. You know, I think that's the hardest thing about research—that sort of willingness to keep going.”
It is this approach that has enabled his lab’s remarkable influence on the field. Dr. Huang’s discovery of a potential new drug for MS, enabled by his willingness to explore a mere hypothesis about an amino acid transporter, and his innovative methodology for labeling MS lesions, developed through numerous trials, shows the importance of perseverance and an indifference to the prospect of failure. By pursuing abstract questions through relentless thought and experimentation, Dr. Huang is helping to spearhead progress in the field of MS research, to provide a better future for patients with neurodegenerative diseases worldwide.
Additional Information/Resources
Find more information about Dr. Huang’s research at https://www.huang-lab.com/
Also check out our past article featuring Dr. Huang!: How Cutting-Edge Research in Washington, D.C. is Reshaping Science and Medicine
