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The Pishesha Lab

As a team, we aspire to expand our understanding of the immune system and harness its potential to combat pathogenic immunity and to produce novel vaccines that address complex infectious agents. We operate at the intersection of four key domains: basic immunology, protein biochemistry, chemical immunology, and engineering.

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Research

Nanobodies (abbreviated VHH, variable heavy domain of heavy chain) are single-chain proteins derived from camelid species that possess antibody-like ability to recognize three-dimensional targets while remaining simple to manufacture and modify. We actively conduct alpaca immunization campaigns and screening efforts to identify new nanobodies that exhibit precise, targeted biological functions. Applying various protein engineering methods, we are expanding the range of applications of these nanobodies as building blocks of therapeutic agents, immune engineering modulators, and as innovative tools for biochemistry and immune imaging. 

In particular, we are exploring the use of nanobody-based strategies to mute unwanted immune responses by fine-tuning where and when cells of the immune system receive anti-inflammatory cues. Our goal is to sustainably counteract the hyperactive immune niche present in various autoimmune diseases. To test the efficacy of our strategy, we use both preclinical mouse models of autoimmune diseases and samples derived from patients. As an immunological counterpoint, we are also investigating the use of our nanobodies as an efficacious vehicle for therapeutics and vaccines against viral and parasitic infections.

Key Publications

Induction of antigen-specific tolerance by nanobody-antigen adducts that target class-II major histocompatibility complexes.

Pishesha N, Harmand T, Smeding LY, Ma W, Ludwig LS, Janssen R, Islam A, Xie YJ, Fang T, McCaul N, Pinney W 3rd, Sugito HR, Rossotti MA, Gonzalez-Sapienza G, Ploegh HL. Nat Biomed Eng. 2021 Nov;5(11):1389-1401. doi: 10.1038/s41551-021-00738-5.

4 July

The first Pishesha Lab BBQ was hosted. Excited for more to come!

1 July

More exciting funding news! The lab has just been awarded the Innovative Research Award from the Rheumatology Research Foundation, which will support our ongoing works on engineering nanobodies to tackle rheumatoid arthritis.

24 June

We are so grateful to have our research supported by the Child Health Research Award from the Charles H. Hood Research Foundation.

18 June

Niklas joins the lab as a Master’s student. So excited to have you, Niklas =)

10 June

Warm welcomes to our newest member, Ayman! Ayman is joining as summer student from Kenyon College.

Recent News

We are thankful for the funding support from

National Multiple Sclerosis Society
Boston Children's Hospital
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If you would like to support our research efforts, please contact us via novalia.pishesha@childrens.harvard.edu

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