Description of Other Expertise

Dr. Sgourakis’ earned his PhD in Biology from Rensselaer Polytechnic Institute with Angel Garcia in 2009, focusing on blending simulation and experimental approaches to study intrinsically disordered proteins. Under mentorship from Nobel Laureate David Baker, he focused on modeling the structures of protein complexes using sparse data, and Adriaan Bax at the NIH, he explored uses of biomolecular NMR spectroscopy for understanding viral immune evasion mechanisms. These experiences laid the foundation for his independent research program focusing on deciphering and targeting the MHC-I antigen progressing and presentation pathway.
During his 5-year tenure at the University of Pennsylvania and Children’s Hospital of Philadelphia, Dr. Sgourakis has steered his work toward immunotherapy applications against pediatric solid tumors, ensuring that his discoveries have real-world therapeutic impact. Dr. Sgourakis’ Lab is part of two international Teams that were selected by the international Cancer Grand Challenges consortium in 2022, and 2025 aiming to develop T cell-based therapeutics. His lab blends structural biology, with computational and protein engineering approaches aiming to restore immune surveillance of intracellular driver oncoproteins.

Description of Research Expertise

The Sgourakis laboratory blends structural approaches, protein engineering, immunoassays and computational biology to elucidate the mechanisms by which tumors process intracellular antigens and present a panel of cell-surface biomarkers that can be targeted for personalized cancer therapy.


Our research centers on understanding the structure and function of the human Major Histocompatibility Complex (MHC), with a goal of facilitating cancer immunotherapy and tuning immune responses to address a variety of diseases. The MHC includes a concentrated group of diverse genes that affect vulnerability to numerous health conditions such as autoimmune disorders, infections, and varied illnesses ranging from cancer to schizophrenia. The MHC’s primary components are Class I and Class II molecules. These molecules are crucial in triggering immune responses by presenting antigenic peptide fragments to T cell receptors, thus signaling an aberrant cellular state. A significant portion of our work focuses on understanding how these molecules are assembled intracellularly, and what functions they serve on the cell surface.


MHC-I proteins are extremely polymorphic (>15,000 known allotypes) in the human population. Each allotype displays a unique repertoire of peptide antigens, ensuring species adaptability to emerging pathogens. However, this complexity challenges the development of robust therapeutic approaches that can cover patients of diverse ethnic backgrounds. A long-term research goal of our laboratory is to gain a detailed atomic-level description of the MHC-I antigen loading process, through our structural and biochemical studies of the chaperones Tapasin and TAPBPR. We have developed two orthogonal approaches employing i) Engineered molecular chaperones or ii) conformationally stabilized “open” MHC-I proteins, that can be readily applied to enable peptide exchange in vitro. The molecular tools generated by the new approaches are significantly advancing our understanding of MHC-I antigen repertoires in different disease settings.

To address existing barriers to clinical translation, we are developing approaches employing engineered MHC-I chaperones to enhance the immunogenicity of classically cold (low T cell infiltration) tumors, such as pediatric neuroblastoma. In a parallel direction, we are designing novel, peptide-focused binding modules targeting tumor-associated pMHC-I antigens for enabling personalized therapeutics using CAR-Ts or Bispecific T cell Engagers (BiTEs).