Anonymous

The lab of Isaac Chiu, AB ’02, PhD ’09, a professor of immunology in the Blavatnik Institute at Harvard Medical School, is breaking new ground in the study of neurodegenerative illnesses, pain, and itch. This work is supported by a generous $1 million dollar gift from an anonymous donor.

Neurodegenerative disease

The PhD thesis of longtime Chiu Lab member Dylan Neel, AB ’15, PhD ’23, MD ’25, laid the groundwork for some of the lab’s most promising recent work on neurodegenerative illnesses. While studying amyotrophic lateral sclerosis (ALS), Neel found that the protein Gasdermin-E triggers an inflammatory cascade that opens pores in mitochondria, leading to axon degeneration and, eventually, neuron death. By reducing the expression of Gasdermin-E genes in a mouse model—thereby suppressing the protein’s production—researchers have managed to slow degeneration. This approach could potentially be applicable not only to ALS but also to Alzheimer’s, cortical diseases, dementia, and many other neurodegenerative disorders.

Pain

The Chiu Lab also demonstrated, in a 2023 paper, a strong connection between pain and microbial infection. “Bacteria facilitate their advance into the central nervous system,” Chiu explains, “by hijacking sensory neurons in the meninges”—the protective layers of tissue surrounding the brain and spinal cord. The lab is currently exploring whether microbes contribute to chronic pain and examining the nervous system’s response to painful stimuli beyond the meninges, particularly in the skin. Early work with mouse models is promising: When treated with antibiotics, mice experience less chronic pain. The lab is also investigating the mechanism underlying chronic pain in Lyme disease (caused by Borrelia burgdorferi) and how botulinum toxin (commonly known as Botox), which blocks the body's local response to nerve signals, might treat infections.

Itch

Another significant area of study involves the bacterial pathogen Staphylococcus aureus. The Chiu Lab demonstrated for the first time a direct connection between microbial infection and itch. Lab members found that S. aureus secretes a protease that directly activates sensory neurons, driving itch and causing skin damage. The bacterium is present in skin lesions in nearly all patients with the chronic condition atopic dermatitis.

“Until recently,” says Chiu, “we believed that the itch associated with atopic dermatitis and eczema arose from the accompanying inflammation of the skin.” Instead, the lab’s research revealed that S. aureus itself directly causes itch by instigating a molecular chain reaction that prompts sensory neurons to signal the urge to scratch. The paper announcing these findings, published in Cell in 2023, attracted significant media attention.

The lab continues to explore the link between bacterial infection and chronic itch. Lab members are examining whether the cascade might lead to downstream allergies; it’s possible that itch-causing bacteria also induce asthma or allergies via damage to the skin.

“We are extremely grateful for this gift,” says Chiu. “The donor’s generous support in this challenging funding landscape empowers us to make important discoveries and progress in science that would not otherwise be possible.”