Seraphine Kamayirese
Postdoctoral Scholar, Bioengineering
Bio
I am a protein and peptide biochemist with a focus on biophysical characterization, structural activity relationship (SAR)study, and design and optimization of peptides targeting disease-relevant proteins. My Ph.D. research focused on designing and optimizing ligands that target the 14-3-3ε protein to disrupt its interaction with the cell cycle regulator CDC25A, an interaction known to suppress apoptosis in squamous cell carcinoma. Inhibiting this pathway is expected to promote apoptosis in cutaneous squamous cell carcinoma. At Stanford University, I am expanding my research to study antimicrobial peptidoids and peptides such as LL-37 and their interactions with amyloid beta peptides, and the potential application of the resulting complexes as antiviral therapeutics. I bring strong experience in rational peptide design, structural activity relationship studies, molecular dynamics simulations, peptides and peptoids synthesis and purification, protein expression, and biophysical assays. My research has led to multiple peer-reviewed publications, presentations at national and international conferences, and awards, including the Young Investigator Poster Award at the American Peptide Symposium.
Professional Education
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Doctor of Philosophy, Creighton University (2024)
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Bachelor of Science, Arizona State University (2019)
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BS, Arizona State University, Biochemistry (2019)
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Ph.D., Creighton University, Biomedical Sciences (2024)
All Publications
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Ligand recognition by 14-3-3 proteins requires negative charges but not necessarily phosphorylation.
FEBS letters
2025; 599 (6): 838-847
Abstract
Protein-protein interactions involving 14-3-3 proteins regulate various cellular activities in normal and pathological conditions. These interactions have mostly been reported to be phosphorylation-dependent, but the 14-3-3 proteins also interact with unphosphorylated proteins. In this work, we investigated whether phosphorylation is required, or, alternatively, whether negative charges are sufficient for 14-3-3ε binding. We substituted the pThr residue of pT(502-510) peptide by residues with a varying number of negative charges and investigated the binding of the peptides to 14-3-3ε using MD simulations and biophysical methods. We demonstrated that at least one negative charge is required for the peptides to bind 14-3-3ε, although phosphorylation is not necessary, and that two negative charges are preferable for high affinity binding. This discovery opens up new approaches for designing peptide-based 14-3-3 protein inhibitors.
View details for DOI 10.1002/1873-3468.15077
View details for PubMedID 39757510
View details for PubMedCentralID PMC11931987
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The Development of CDC25A-Derived Phosphoseryl Peptides That Bind 14-3-3ε with High Affinities.
International journal of molecular sciences
2024; 25 (9)
Abstract
Overexpression of the 14-3-3ε protein is associated with suppression of apoptosis in cutaneous squamous cell carcinoma (cSCC). This antiapoptotic activity of 14-3-3ε is dependent on its binding to CDC25A; thus, inhibiting 14-3-3ε - CDC25A interaction is an attractive therapeutic approach to promote apoptosis in cSCC. In this regard, designing peptide inhibitors of 14-3-3ε - CDC25A interactions is of great interest. This work reports the rational design of peptide analogs of pS, a CDC25A-derived peptide that has been shown to inhibit 14-3-3ε-CDC25A interaction and promote apoptosis in cSCC with micromolar IC50. We designed new peptide analogs in silico by shortening the parent pS peptide from 14 to 9 amino acid residues; then, based on binding motifs of 14-3-3 proteins, we introduced modifications in the pS(174-182) peptide. We studied the binding of the peptides using conventional molecular dynamics (MD) and steered MD simulations, as well as biophysical methods. Our results showed that shortening the pS peptide from 14 to 9 amino acids reduced the affinity of the peptide. However, substituting Gln176 with either Phe or Tyr amino acids rescued the binding of the peptide. The optimized peptides obtained in this work can be candidates for inhibition of 14-3-3ε - CDC25A interactions in cSCC.
View details for DOI 10.3390/ijms25094918
View details for PubMedID 38732131
View details for PubMedCentralID PMC11084659
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Optimizing Phosphopeptide Structures That Target 14-3-3ε in Cutaneous Squamous Cell Carcinoma.
ACS omega
2024; 9 (2): 2719-2729
Abstract
14-3-3ε is involved in various types of malignancies by increasing cell proliferation, promoting cell invasion, or inhibiting apoptosis. In cutaneous squamous cell carcinoma (cSCC), 14-3-3ε is overexpressed and mislocalized from the nucleus to the cytoplasm where it interacts with the cell division cycle 25 A (CDC25A) and suppresses apoptosis. Hence, inhibition of the 14-3-3ε-CDC25A interaction is an attractive target for promoting apoptosis in cSCC. In this work, we optimized the structure of our previously designed inhibitor of the 14-3-3ε-CDC25A interaction, pT, a phosphopeptide fragment corresponding to one of the two binding regions of CDC25A to 14-3-3ε. Starting from pT, we developed peptide analogs that bind 14-3-3ε with nanomolar affinities. Peptide analogs were designed by shortening the pT peptide and introducing modifications at position 510 of the pT(502-510) analog. Both molecular dynamics (MD) simulations and biophysical methods were used to determine peptide binding to 14-3-3ε. Shortening the pT peptide from 14 to 9 amino acid residues resulted in a peptide (pT(502-510)) that binds 14-3-3ε with a KD value of 45.2 nM. Gly to Phe substitution in position 510 of pT(502-510) led to further improvement in affinity (KD: 22.0 nM) of the peptide for 14-3-3ε. Our results suggest that the designed peptide analogs are potential candidates for inhibiting 14-3-3ε-CDC25A interactions in cSCC cells and thus inducing their apoptosis.
View details for DOI 10.1021/acsomega.3c07740
View details for PubMedID 38250398
View details for PubMedCentralID PMC10795040