Written by Dr. Tam Maiuri
Edited by Dr. Kaitlyn Deschamps
Uninterrupted: Dr. Chris Kay on Somatic Expansion, an Unusual Brain Bank, and the Next Chapter of HD Genetics
Thirty feet from Dr. Chris Kay’s desk is a room where brains are dissected, in the same way, every single time, without exception. When a donated brain arrives in that room at the Centre for Brain Research at the University of Auckland, straight from Auckland City Hospital across the road, this brain bank goes to work. Each block of tissue is logged with precise spatial coordinates — not just which brain structure it came from, but exactly where within that structure, every time.
This is not how most brain banks operate. Most brain banks approximate the location of the samples and have protocols that shift depending on who was working at the time. This contrast in operational standards begins to explain why Chris eventually moved to New Zealand, home to the University of Auckland.
The Persistence of a Question
Chris grew up in the United States and completed his undergraduate degree in Florida, where he joined an Alzheimer’s disease genetics lab. What captivated him wasn’t any particular protein being studied, but the deeper idea that a single genetic change could trigger a cascade of events that could reshape a person’s brain anatomy and their personality.
After graduating, Chris moved to Vancouver for personal reasons: friends and a love of the Pacific Northwest. Once there, he searched “Vancouver genetics brain disease,” and one name surfaced immediately: Dr. Michael Hayden at the University of British Columbia. What followed was a fairly relentless campaign to join the Hayden lab. Chris wrote letters that went unanswered (applications from prominent institutions were normal, so a state university in Florida didn’t stand out). He applied for a technician position, but didn’t get it. When the same posting appeared a year later, he applied again, pointing out in the cover letter that he recognized it. This time, he got an interview and immediately clicked with his interviewer. Before being hired, Chris was asked to volunteer for two unpaid weeks, something he suspects was an informal test of motivation. He accepted and passed without complaint.
Once inside the lab, Chris found his niche in Huntington’s disease (HD) haplotypes: the patterns of genetic variation surrounding the disease-causing mutation across populations. At the time, most of the field was focused on the huntingtin protein itself, specifically on what goes wrong once the mutation is expressed as a protein. Haplotypes posed a different question entirely: one of genetics.
The Chapter No One Expected
HD genetics has been declared “finished” more than once: first after the gene was identified in 1993, then again after genome-wide association studies mapped genetic modifiers of disease onset. Each time, the story grew more complex. Chris finds that this expansion is energizing rather than discouraging.
The current frontier is somatic expansion. The CAG repeat that causes HD isn’t a fixed length in every cell of the body. In certain neurons, the repeat continues to lengthen over a person’s lifetime, and remarkably, those neurons are the ones that die in the disease. Chris is fairly convinced that this expansion is causal, though he is careful in how he holds that view. “It would be a heck of a coincidence,” he says, while acknowledging that a definitive mechanism has yet to be proven.
Without Interruption
The HDSA Berman-Topper Family HD Career Development Fellowship provided Chris with three years of protected research time and supported two primary lines of inquiry. “Without interruption” carries a double meaning Chris didn’t plan but can’t ignore: the fellowship gave him uninterrupted time, and the science he pursued centers on a literal missing interruption in the genetic code.
In most people, the CAG repeat in the HD gene follows a consistent pattern: a long stretch of CAG, followed by a single CAA, and then one final CAG. That CAA acts as a sort of genetic speed bump. In a small subset of patients, it’s missing; the sequence runs straight through without interruption. These cases are known as “loss of interruption” (LOI for short), and they seem to cause symptoms to develop earlier and with more severity.
Chris’s first question was whether the missing speed bump is associated with increased somatic expansion in the neurons most vulnerable in HD. A recent bioRxiv preprint he co-authored with Jessica Dawson, Michael Hayden, and colleagues, suggests that it is. In LOI patients, the proportion of cells most affected in HD (medium spiny neurons) shows a roughly fivefold increase in large somatic CAG expansion compared with non-LOI patients with similar inherited repeat lengths. Neuron counts in the caudate are also lower, meaning fewer neurons survive in that region. Whether this expansion directly kills those cells isn’t yet determined, but the association is hard to ignore.
His second line of inquiry asked whether unusual proteins produced by the uninterrupted CAG repeat might explain the severity of LOI cases. Those results were mostly negative. Chris views that outcome as informative rather than disappointing: ruling something out as a possibility is a large part of how science advances.
A Brain Bank Unlike Any Other
Most brain banks hold tissue that could be best described as diffuse: yes, a sample of caudate, but from where exactly? The Auckland brain bank is different. It tracks spatial coordinates, relies on standardized dissection protocols, and has decades of consistent practice behind it. That kind of resource can’t be created overnight. You can adopt the same methods today, doing it the Auckland way, but it would take decades to achieve something comparable.
Chris’s specific question, how somatic expansion varies within brain regions, not merely between them, requires this level of precision. Here, spatial detail isn’t a luxury; it’s what makes the question answerable.
Perpetual Giving
Last month, Chris watched a brain dissection, an experience that stayed with him. The technicians performing these procedures are extremely precise: the gyri (the brain’s characteristic folds and ridges) aren’t random, they correspond to specific functions, and each cut is placed so that every sample lands exactly where it should. The pieces of tissue Chris worked with during his fellowship were about the size of two grains of rice. And yet even fragments that small can support numerous studies across multiple labs, including projects that rely on technology that may not even exist when the tissue was donated. Chris calls himself and his colleagues “custodians” of these samples. It’s a word he uses carefully, because the people managing the collection at the Auckland bank take this responsibility seriously. The institute monitors tissue use carefully, fields requests, and makes sure nothing is depleted carelessly. The goal is for each donation to continue giving — across decades and across questions that no one has yet thought to ask.
Looking Ahead
Clinical trials targeting somatic expansion are now underway, and Chris watches their progress with a mix of excitement and nerves. His concern isn’t failure itself, but misinterpretation. A negative trial result might lead the field to abandon a valid target when the real issue could have been timing: treatment introduced too late or applied in the wrong way. A negative trial and a wrong target aren’t the same thing.
Looking ahead, Chris plans to build on a resource the Auckland bank has been quietly assembling: genetic profiles, drawn from complete genome sequencing, for roughly half of its donors. He will use these to examine how modifier variants affect somatic expansion in brain tissue — including variants in the mismatch repair genes that current clinical trials are targeting. Some of these variants are common enough to appear across a meaningful share of the population, which means they could shape how trial results look from patient to patient. When that data arrives, his goal is simple: make sure the science isn’t interrupted by the wrong conclusion.
