Research

At the Sgourakis Lab, we develop methods to address the extreme diversity of intracellular antigens, which can be processed and displayed by the highly polymorphic proteins of the human Major Histocompatibility Complex (human leukocyte antigens, HLAs). Our overarching goal is to identify and target robust surface biomarkers for cancer immunotherapy that can be applied to patients from different ethnic groups.

Targeting tumor-associated antigens

Tumors can display mutated or overexpressed protein fragments on the cell surface via peptide/MHC complexes. To target these tumor-specific pMHC molecules, we are designing receptor-based therapeutics. Additionally, we are developing computational tools that predict and rationalize our experimental outcomes.

MHC protein design

We are pursuing protein design efforts focused on the MHC-I molecule to create ligand exchange platforms. This will enable us to screen and select antigenic peptides and to monitor antigen-specific T cells.

Antigen processing

Tapasin and TAPBPR are chaperones involved in the selection and optimization of the peptide repertoire for MHC molecules. We are focused on understanding the molecular mechanism behind this process to inform the creation of modified proteins useful for therapeutic development.

Our computational tools

HLA3DB: https://hla3db.research.chop.edu/

  • An automated, curated database of peptide/MHC-I structures

RepPred: https://zenodo.org/record/8372876

  • Structure prediction of peptide/HLA complexes

MAUS: https://maus.research.chop.edu/

  • Automated methyl assignment of NOESY data