Harvard Catalyst Profiles

The Pishesha Lab at the Division of Immunology, Boston Children’s Hospital, aims to deepen our understanding of the immune system and harness its potential to combat immune-mediated diseases. Our work lies at the intersection of four key fields: basic immunology, protein biochemistry, chemical immunology, and engineering. A central tool in our research is nanobodies (abbreviated VHH, or variable heavy domain of heavy chain), single-chain proteins derived from camelids. These nanobodies possess antibody-like abilities to recognize three-dimensional targets, while being simple to manufacture and modify. We conduct alpaca immunization campaigns and screening efforts to identify new nanobodies with precise, targeted biological functions. Through various protein engineering methods, we expand the applications of these nanobodies as therapeutic agents, immune engineering modulators, and innovative tools for biochemistry and non-invasive positron emission tomography (PET)-based immune imaging. In particular, we are exploring nanobody-based immunotherapy strategies to modulate unwanted immune responses by controlling where and when immune cells receive anti-inflammatory cues. Our goal is to sustainably counteract hyperactive immune niches in autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and allergies. To assess the effectiveness of our approach, we use preclinical mouse models of autoimmune diseases and patient-derived samples. Additionally, we are investigating the use of nanobodies as vehicles for therapeutics and vaccines against viral and parasitic infections. Students will gain hands-on experience in designing novel immunotherapies, generating engineered constructs, and testing them in both animal and human disease models.