Connections. Spectraplakins sit at the interface of architecture and motion inside a cell. They do not merely hold structures together but coordinate how the cytoskeleton rearranges itself when neu…

VUS. The story begins with a patient in clinic. A young child with severe epilepsy, carrying a variant in SCN1A, the classic gene for Dravet Syndrome. But the variant is labeled a variant of uncertain significance (VUS). Dravet Syndrome is a clinical diagnosis, and the treatments we have today do not hinge on whether the variant is clearly pathogenic or not.

Singularity. A few months ago, Sam Altman, the CEO of OpenAI, published a short essay about the future of artificial intelligence. His central message was a gentle role for AI—a vision in which technology supports us quietly in the background rather than staging some dramatic takeover of human life. What caught my attention, however, was not the word “gentle” but the word “singularity.” For science fiction readers, this term carries weight.

ANE. A rare complication with hidden genetic clues. Imagine a healthy child who goes to bed with a fever and wakes up unable to recognize their parents, slipping rapidly into coma. This is the terrifying course of acute necrotizing encephalopathy (ANE), one of the most severe neurological complications of influenza. In a recent study, children with influenza who developed ANE showed an unexpected pattern: nearly half of those tested carried genetic variants that might predispose them to this devastating complication.

A paradox in the hippocampus. Immature dentate granule cells are often described as the “plasticity reserve” of the hippocampus. They provide a pool of neurons that integrate into existing circuits, supporting learning, memory, and repair. In neurological disease, these cells have been suggested to buffer against injury or degeneration. In a recent publication, researchers showed that the hippocampus continues to generate new neurons throughout life, but that the molecular instructions for doing so vary dramatically across species.

Neurodevelopment. Congenital heart disease (CHD) refers to a broad group of structural abnormalities of the heart that are present at birth and affect approximately 1% of all live births. Over the past two decades, advances in neonatal surgery and perioperative care have dramatically increased survival rates. Yet this success has revealed an important challenge, and focus has gradually shifted from the heart alone to the brain.

Rehoboth. It has been a while since I posted my annual post-beach-vacation thoughts about how my experiences at the shore made me think about science. I initially started these posts after a vacation in Marielyst, Denmark when I realized that my sandcastle building skills were not appreciated as much as I thought. This reminded me that similar things happen with our scientific achievements.

Fluency. When we think of stuttering, we might first think of speech therapy, of pauses and repetitions, and of the courage it takes to speak when words get stuck. But what if we could step back and see its genetic architecture laid out across the globe? A recent study looked at the genetics of stuttering at an unprecedented scale: over 1.1 million individuals, including almost 100,000 people who self-reported a history of stuttering.

The clock gene. Every cell in the human body keeps time. This intrinsic rhythm is roughly 24 hours long and driven by the molecular circadian clock: a transcriptional feedback loop that helps regulate sleep, metabolism, and hormone release. But what happens when these timekeepers stop working? In a recent study, we explored the role of BMAL1 (ARNTL), a core circadian regulator, in neurodevelopmental disorders.

Monastic. I am now roughly one month into the first real job of my life. I celebrated this transition by spending a week with my family in Kamp-Lintfort, Germany, a small town at the Western edge of the Ruhr area known for its coal mining heritage and Cistercian abbey. After two decades of training roles and academic positions that were either time-limited or contingent, I was tenured at the University of Pennsylvania in July 2025.

Paralogs. Every week in our variant review meetings, we encounter a familiar issue: understanding a missense variant of uncertain significance. Unless it matches a known disease-associated variant or is found to be de novo, our confidence often stalls. But what happens if we stopped looking at genes in isolation? In a recent publication, we had the opportunity to explore this idea by looking at paralogs and variants at identical sites across gene families, and we found evidence that was strong enough to be included in the official ACMG/AMP variant curation criteria.