A hidden endocrine state of the brain drives age-related neurodegeneration

Our vision is grounded in the profound impact that circulating factors, such as hormones, have on neural circuits. We seek to decode how these signals tune circuits to promote healthy brain function, and how this tuning goes awry in disease. By uncovering the rules of this body-brain communication, we aim to harness these potent, naturally evolved pathways as new strategies to protect brain health, preserve cognitive function, and treat neurological disease.

Daniel Hochbaum is an Assistant Professor at Harvard Medical School and a Principal Investigator at Beth Israel Deaconess Medical Center. A physicist-turned-neurobiologist, he earned his PhD at Harvard, pioneering tools to map bioelectric phenomena from bacteria to brains, and then led their translation as Chief Scientific Officer of Q-State (now Quiver) Biosciences. As a Junior Fellow in the Harvard Society of Fellows, he integrated molecular, circuit, and quantitative behavioral approaches to show how sensory experience and hormonal state reshape neural circuitry. His lab now investigates how circulating signals like hormones coordinate brain and body, why this coupling frays with aging and disease, and how restoring it can improve function.

The aging brain is vulnerable to memory loss, cognitive decline, and neurodegenerative conditions like Alzheimer’s disease. While most research focuses on misfolded proteins, inflammation, and synaptic damage, a critical but overlooked factor is how aging and disease reshape hormonal signals that support brain health.

Our project explores the hypothesis that thyroid hormone signaling can decline locally within the brain creating a hidden endocrine state, invisible to standard blood tests, that drives circuit dysfunction and neurodegeneration. We will determine how this state arises, how it disrupts neural circuits and behavior, and whether restoring thyroid levels locally in the brain can reverse synaptic pathology and cognitive deficits in models of neurodegeneration. By targeting this previously unrecognized mechanism, our work aims to pioneer new neuroendocrine therapies that preserve cognitive function, slow neurodegeneration, and improve quality of life as we age.

"To me, impact is discovering biological principles that deliver durable benefits to human health.”