The Pishesha Lab

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Nanobodies (abbreviated as VHH, variable heavy domain of heavy chain) are single-chain proteins derived from camelid species. They combine antibody-like precision in recognizing three-dimensional targets with simplicity of manufacturing and modification. At the Pishesha Lab, we actively conduct alpaca immunization campaigns and screening efforts to identify nanobodies with precise and targeted biological functions. Beyond developing nanobodies and their derivatives for our own research, we collaborate extensively within the Division of Immunology, across Boston Children’s Hospital and Harvard Medical School, with labs in the Greater Boston area, and worldwide.

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Using protein engineering, we modify nanobodies to create therapeutic agents, immune modulators, and innovative tools for biochemistry and immune imaging. Specifically, we focus on nanobody-based strategies to suppress unwanted immune responses by precisely controlling when and where immune cells receive anti-inflammatory cues. Our goal is to generate durable immune tolerance that sustainably counteract the hyperactive immune environments characteristic of various autoimmune diseases. To evaluate these strategies, we utilize preclinical mouse models and, where possible, patient-derived samples. As an immunological counterpoint, we also investigate nanobodies to enhance immune responses, not only in vaccine settings but also to address the suboptimal immune environments often associated with various cancers.