Gita Abhiraman is currently an MD/PhD candidate in the lab of Dr. Christopher Garcia, where she studies cytokine receptor structure, signaling, and engineering. She is a PhD Candidate in the Immunology Program at Stanford. Gita received her bachelor's degree in physics with a focus in biophysics from Harvard University in 2018. She previously studied tumor-immune dynamics and helped to engineer sortase, a bacterial enzyme, for in vivo labeling under the mentorship of Dr. Stephanie Dougan at the Dana-Farber Cancer Institute.
Honors & Awards
Hertz Fellow, The Fannie and John Hertz Foundation (2021)
Education & Certifications
Bachelor of Arts, Harvard University (2018)
A structural blueprint for interleukin-21 signal modulation.
2023; 42 (6): 112657
Interleukin-21 (IL-21) plays a critical role in generating immunological memory by promoting the germinal center reaction, yet clinical use of IL-21 remains challenging because of its pleiotropy and association with autoimmune disease. To better understand the structural basis of IL-21 signaling, we determine the structure of the IL-21-IL-21R-γc ternary signaling complex by X-ray crystallography and a structure of a dimer of trimeric complexes using cryo-electron microscopy. Guided by the structure, we design analogs of IL-21 by introducing substitutions to the IL-21-γc interface. These IL-21 analogs act as partial agonists that modulate downstream activation of pS6, pSTAT3, and pSTAT1. These analogs exhibit differential activity on T and B cell subsets and modulate antibody production in human tonsil organoids. These results clarify the structural basis of IL-21 signaling and offer a potential strategy for tunable manipulation of humoral immunity.
View details for DOI 10.1016/j.celrep.2023.112657
View details for PubMedID 37339051
Structure-based decoupling of the pro- and anti-inflammatory functions of interleukin-10.
Science (New York, N.Y.)
2021; 371 (6535)
Interleukin-10 (IL-10) is an immunoregulatory cytokine with both anti-inflammatory and immunostimulatory properties and is frequently dysregulated in disease. We used a structure-based approach to deconvolute IL-10 pleiotropy by determining the structure of the IL-10 receptor (IL-10R) complex by cryo-electron microscopy at a resolution of 3.5 angstroms. The hexameric structure shows how IL-10 and IL-10Ralpha form a composite surface to engage the shared signaling receptor IL-10Rbeta, enabling the design of partial agonists. IL-10 variants with a range of IL-10Rbeta binding strengths uncovered substantial differences in response thresholds across immune cell populations, providing a means of manipulating IL-10 cell type selectivity. Some variants displayed myeloid-biased activity by suppressing macrophage activation without stimulating inflammatory CD8+ T cells, thereby uncoupling the major opposing functions of IL-10. These results provide a mechanistic blueprint for tuning the pleiotropic actions of IL-10.
View details for DOI 10.1126/science.abc8433
View details for PubMedID 33737461
Generation of Ca2+-independent sortase A mutants with enhanced activity for protein and cell surface labeling
2017; 12 (12): e0189068
Sortase A, a calcium-dependent transpeptidase derived from Staphylococcus aureus, is used in a broad range of applications, such as the conjugation of fluorescent dyes and other moieties to proteins or to the surface of eukaryotic cells. In vivo and cell-based applications of sortase have been somewhat limited by the large range of calcium concentrations, as well as by the often transient nature of protein-protein interactions in living systems. In order to use sortase A for cell labeling applications, we generated a new sortase A variant by combining multiple mutations to yield an enzyme that was both calcium-independent and highly active. This variant has enhanced activity for both N- and C-terminal labeling, as well as for cell surface modification under physiological conditions.
View details for DOI 10.1371/journal.pone.0189068
View details for Web of Science ID 000417033200027
View details for PubMedID 29200433
View details for PubMedCentralID PMC5714338