Explore Research Innovation at the David Geffen School of Medicine
Manish Butte, MD, PhDAssociate Professor, Pediatrics and Microbiology/Immunology/Molecular Genetics, David Geffen School of Medicine at UCLA
A practicing immunologist, Dr. Butte uses advanced investigative techniques and next-generation diagnostic tools to move medical mysteries into treatable territory.
Dr. Butte runs the only lab in the world studying the influence of tissue mechanics on immune system function. By defining the mechanical forces driving disease and immune response, Dr. Butte hopes to change the way we treat and heal a panoply of human disorders.
Dr. Butte investigates the mechanisms of disease on a molecular level, tracking disorders from the mutation of one DNA nucleotide to the subsequent impairment of T and B cell functionality. He isolates the underpinning systemic causes of rare immune diseases, developing treatments for one-of-a-kind patients considered medical mysteries. He is even designing a process that uses humanized mice to make it faster to validate, and therefore treat, rare human genetic diseases.
Photo from the Butte Lab at UCLA.
Every case stimulates Dr. Butte’s heart and his intellect. He keeps patients’ pictures—and exomes—pinned to his walls.
“These cases are experiments of nature. If we can see how these diseases work, then we can see how nature works,” says Dr. Butte.
A drive to learn how nature—specifically the immune system—works drive Dr. Butte’s explorations in the budding field of mechanobiology.
Dr. Butte believes mechanobiology, the study of how mechanical forces influence cells and tissues, will contribute to an uncharted understanding of immune responses, including what makes a T cell act.
Using atomic force microscopy, the Butte Lab imaged T cells in motion and found they give antigen-presenting cells forceful "bear hugs" to extract information. Additionally, the lab's observations proved the molecular bear hug critical to information gathering; T cells require both force and contact to activate receptors and access antigen. Read more in T Cell Activation Requires Force Generation, published in the Journal of Cell Biology.
The researchers also found that tissue mechanics, specifically a tissue's stiffness or softness, control a T cell's ability to administer "molecular bear hugs" and collect information necessary to make a sound response decision.
The Butte Lab hypothesizes that tissue mechanics influence T cell responses in nearly all diseases, from cancer to autoimmune disorders. They suggest:
By studying tissue mechanics and learning how to modulate them, the Butte Lab hopes to inform fields trying to activate the immune system and fields trying to suppress it.
Recently, the team pinpointed an enzyme—cofilin—that controls cytoskeletal rigidity, a deciding factor in a T cell’s ability to engage with antigen presenting cells. Read more in Cytoskeletal Adaptivity Regulates T Cell Receptor Signaling, published in Science Signaling.
The Butte Lab aims to turn cofilin on and off, dialing the immune system up or down depending on the patient. This modulation of the mechanical forces driving immune response would help fight any disease and even boost vaccination success.
Such control would lead to infinite possibilities and infinite potential interventions,” says Dr. Butte.
Dr. Butte studies universals—the mechanisms driving immune function in all diseases. By understanding these mechanisms, he aims to develop treatments for a gamut of immunological issues. With each mutation, force, or enzyme uncovered, Dr. Butte is sketching an evidence-based blueprint for treating any patient.
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