Andras Fiser, Ph.D.

The Mechanistic Basis of Molecular Recognition

Our laboratory investigates the fundamental principles governing how proteins specifically recognize their cognate ligands within the crowded cellular environment. Key objectives include deciphering the evolutionary trajectories of protein interfaces, identifying the structural and physico-chemical determinants that differentiate these interfaces from the rest of the protein surface, and pinpointing the exact residues that dictate binding specificity. Ultimately, we leverage these insights to rationally engineer protein and peptide interfaces with customized specificities and enhanced selectivities.

The Molecular Basis of Receptor-Ligand Recognition in the Immunological Synapse

Our long-term goal is to elucidate the structural and physical principles underlying molecular recognition and selectivity at the immunological synapse. This research focuses on the discovery of novel receptor-ligand interactions and the translation of these findings into engineered, surgically defined mutants. By selectively tailoring binding affinities and selectivities, we aim to develop a new class of targeted biologic therapeutics.

1. Ramos KE, Nandigrami P, Najafian A, Lai JR, Fiser A.
   Optimization of a sarbecovirus llama nanobody-antigen binding interface via a combined computational and phage display protein engineering approach.
   Proc Natl Acad Sci U S A. 2025 Jul 15;122(28)
2. Nandigrami P, Goldman ID, Fiser A. 
   Mechanistic insights into mutation in the proton-coupled folate transporter (SLC46A1) causing hereditary folate malabsorption.
   J Biol Chem. 2025 Mar;301(3):108280.
3. Grudman S, Fiser A. 
   Conservation of Human IgSF Proteins Throughout Eukaryotic Evolution.
   Genome Biol Evol. 2026 Jun 2;18(6)
4. Grudman S, Madrid-Aliste C, Fiser A.
   Overcoming research bias: The untapped potential of biomedically important but understudied proteins. 
   iScience. 2025 Aug 14;28(9):113210.
5. Nandigrami P, Fiser A
   Assessing the functional impact of protein binding site definition.. 
   Protein Sci. 2024 Jun;33(6):e5026.
6. Viswanathan R, Carroll M, Roffe A, Fajardo JE, Fiser A. 
   Computational prediction of multiple antigen epitopes.
   Bioinformatics. 2024 Oct 1;40(10)
7. Grudman S, Fajardo JE, Fiser A. 
   Optimal selection of suitable templates in protein interface prediction.
   Bioinformatics. 2023 Sep 2;39(9)
8. Grudman S, Fajardo JE, Fiser A.
   INTERCAAT: identifying interface residues between macromolecules. 
   Bioinformatics. 2022 Jan 3;38(2):554-555.
9. Gil N, Shrestha R, Fiser A
   Estimating the accuracy of pharmacophore-based detection of cognate receptor-ligand pairs in the immunoglobulin superfamily.
   Proteins (2021) 89(6) : 632-638
10. Shrestha R, Fajardo JE, Fiser A
    Residue-based pharmacophore approaches to study protein-protein interactions.
    Curr Opin Struct Biol (2021) 67, 205-211
11. Shrestha R, Garrett-Thomson S, Liu W, Almo SC, Fiser A. 
    Allosteric regulation of binding specificity of HVEM for CD160 and BTLA ligands upon G89F mutation.
    Curr Res Struct Biol. 2021 Nov 13;3:337-345.
12. Shrestha R, Garrett-Thomson SC, Liu W, Almo SC, Fiser A
    Redesigning HVEM Interface for Selective Binding to LIGHT, BTLA, and CD160.
    Structure (2020) 28(11) : 1197-1205.e2
13. Shrestha R, Garrett SC, Almo SC, Fiser A
    Computational Redesign of PD-1 Interface for PD-L1 Ligand Selectivity.
    Structure (2019) 27(5) : 829-836.e3
14. Viswanathan R, Fajardo E, Steinberg G, Haller M, Fiser A
    Protein-protein binding supersites.
    PLoS Comput Biol (2019) 15(1) : e1006704