Derbyshire Lab

The Derbyshire Lab uses both chemical tools and biological methods to uncover novel aspects of malaria parasite biology with the ultimate aim of identifying druggable targets. Projects range from developing assays for phenotypic and target-based screens to exploring biological pathways and identifying small molecules with potential therapeutic value. Their interdisciplinary collaborative program integrates chemical biology, molecular biology and biochemistry to globally interrogate parasite biology.

• Schroeder, Erin A., Maria Toro-Moreno, Rene Raphemot, Kayla Sylvester, Isabel C. Colón, and Emily R. Derbyshire. “Toxoplasma and Plasmodium associate with host Arfs during infection.” MSphere, February 2024, e0077023. https://doi.org/10.1128/msphere.00770-23.

• Ong, Han Wee, Chandi de Silva, Krisha Avalani, Frank Kwarcinski, Christopher R. Mansfield, Michael Chirgwin, Anna Truong, Emily R. Derbyshire, Reena Zutshi, and David H. Drewry. “Characterization of 2,4-Dianilinopyrimidines Against Five P. falciparum Kinases PfARK1, PfARK3, PfNEK3, PfPK9, and PfPKB.” ACS Medicinal Chemistry Letters 14, no. 12 (December 2023): 1774–84. https://doi.org/10.1021/acsmedchemlett.3c00354.

• D’Ambrosio, Hannah K., Aaron M. Keeler, and Emily R. Derbyshire. “Examination of Secondary Metabolite Biosynthesis in Apicomplexa.” Chembiochem : A European Journal of Chemical Biology 24, no. 17 (September 2023): e202300263. https://doi.org/10.1002/cbic.202300263.

• Keeler, Aaron M., Porter E. Petruzziello, Elizabeth G. Boger, Hannah K. D’Ambrosio, and Emily R. Derbyshire. “Exploring the Chain Release Mechanism from an Atypical Apicomplexan Polyketide Synthase.” Biochemistry 62, no. 17 (September 2023): 2677–88. https://doi.org/10.1021/acs.biochem.3c00272.

• Mansfield, Christopher R., Michael E. Chirgwin, and Emily R. Derbyshire. “Labeling strategies to track protozoan parasite proteome dynamics.” Current Opinion in Chemical Biology 75 (August 2023): 102316. https://doi.org/10.1016/j.cbpa.2023.102316.

• Viswanathan, Neil K., Michael E. Chirgwin, Julia Gibbs, Brianna N. Kalaj, Sierra Durham, Jennifer Tran, Maximillian Gomez, et al. “Synthesis and activity of β-carboline antimalarials targeting the Plasmodium falciparum heat shock 90 protein.” Bioorganic & Medicinal Chemistry Letters 92 (August 2023): 129410. https://doi.org/10.1016/j.bmcl.2023.129410.

• Keeler, Aaron M., Hannah K. D’Ambrosio, Jack G. Ganley, and Emily R. Derbyshire. “Characterization of Unexpected Self-Acylation Activity of Acyl Carrier Proteins in a Modular Type I Apicomplexan Polyketide Synthase.” ACS Chemical Biology 18, no. 4 (April 2023): 785–93. https://doi.org/10.1021/acschembio.2c00783.

• Ong, Han Wee, Anna Truong, Frank Kwarcinski, Chandi de Silva, Krisha Avalani, Tammy M. Havener, Michael Chirgwin, et al. “Discovery of potent Plasmodium falciparum protein kinase 6 (PfPK6) inhibitors with a type II inhibitor pharmacophore.” European Journal of Medicinal Chemistry 249 (March 2023): 115043. https://doi.org/10.1016/j.ejmech.2022.115043.

• Galal, Kareem A., Anna Truong, Frank Kwarcinski, Chandi de Silva, Krisha Avalani, Tammy M. Havener, Michael E. Chirgwin, et al. “Identification of Novel 2,4,5-Trisubstituted Pyrimidines as Potent Dual Inhibitors of Plasmodial PfGSK3/PfPK6 with Activity against Blood Stage Parasites In Vitro.” Journal of Medicinal Chemistry 65, no. 19 (October 2022): 13172–97. https://doi.org/10.1021/acs.jmedchem.2c00996.

• Chirgwin, Michael E., Erin A. Schroeder, and Emily R. Derbyshire. “Cut it out! A CRISPR-Cas9 screen identifies host regulators of the Plasmodium liver stage.” Cell Chemical Biology 29, no. 9 (September 2022): 1365–67. https://doi.org/10.1016/j.chembiol.2022.08.005.

• Mughal, Haseeb, Elise C. Bell, Khadija Mughal, Emily R. Derbyshire, and Joel S. Freundlich. “Random Forest Model Predictions Afford Dual-Stage Antimalarial Agents.” ACS Infectious Diseases 8, no. 8 (August 2022): 1553–62. https://doi.org/10.1021/acsinfecdis.2c00189.

• Tye, Mark A., N Connor Payne, Catrine Johansson, Kritika Singh, Sofia A. Santos, Lọla Fagbami, Akansha Pant, et al. “Elucidating the path to Plasmodium prolyl-tRNA synthetase inhibitors that overcome halofuginone resistance.” Nature Communications 13, no. 1 (August 2022): 4976. https://doi.org/10.1038/s41467-022-32630-4.

• Schroeder, Erin A., Michael E. Chirgwin, and Emily R. Derbyshire. “Plasmodium's fight for survival: escaping elimination while acquiring nutrients.” Trends in Parasitology 38, no. 7 (July 2022): 544–57. https://doi.org/10.1016/j.pt.2022.04.004.

• D’Ambrosio, Hannah K., Jack G. Ganley, Aaron M. Keeler, and Emily R. Derbyshire. “Erratum: A single amino acid residue controls acyltransferase activity in a polyketide synthase from Toxoplasma gondii.” IScience 25, no. 7 (July 2022): 104608. https://doi.org/10.1016/j.isci.2022.104608.

• D’Ambrosio, Hannah K., Jack G. Ganley, Aaron M. Keeler, and Emily R. Derbyshire. “A single amino acid residue controls acyltransferase activity in a polyketide synthase from Toxoplasma gondii.” IScience 25, no. 6 (June 2022): 104443. https://doi.org/10.1016/j.isci.2022.104443.

• Lu, Kuan-Yi, Christopher R. Mansfield, Michael C. Fitzgerald, and Emily R. Derbyshire. “Chemoproteomics for Plasmodium Parasite Drug Target Discovery.” Chembiochem : A European Journal of Chemical Biology 22, no. 16 (August 2021): 2591–99. https://doi.org/10.1002/cbic.202100155.

• Bang, Sangsu, Christopher R. Donnelly, Xin Luo, Maria Toro-Moreno, Xueshu Tao, Zilong Wang, Sharat Chandra, Andrey V. Bortsov, Emily R. Derbyshire, and Ru-Rong Ji. “Activation of GPR37 in macrophages confers protection against infection-induced sepsis and pain-like behaviour in mice.” Nat Commun 12, no. 1 (March 17, 2021): 1704. https://doi.org/10.1038/s41467-021-21940-8.

• Sylvester, Kayla, Steven P. Maher, Dora Posfai, Michael K. Tran, McKenna C. Crawford, Amélie Vantaux, Benoît Witkowski, Dennis E. Kyle, and Emily R. Derbyshire. “Characterization of the Tubovesicular Network in Plasmodium vivax Liver Stage Hypnozoites and Schizonts.” Frontiers in Cellular and Infection Microbiology 11 (January 2021): 687019. https://doi.org/10.3389/fcimb.2021.687019.

• Lu, Kuan-Yi, Charisse Flerida A. Pasaje, Tamanna Srivastava, David R. Loiselle, Jacquin C. Niles, and Emily Derbyshire. “Phosphatidylinositol 3-phosphate and Hsp70 protect Plasmodium falciparum from heat-induced cell death.” ELife 9 (September 2020): e56773. https://doi.org/10.7554/elife.56773.

• Ganley, Jack G., Ashmita Pandey, Kayla Sylvester, Kuan-Yi Lu, Maria Toro-Moreno, Sina Rütschlin, James M. Bradford, et al. “A Systematic Analysis of Mosquito-Microbiome Biosynthetic Gene Clusters Reveals Antimalarial Siderophores that Reduce Mosquito Reproduction Capacity.” Cell Chemical Biology 27, no. 7 (July 2020): 817-826.e5. https://doi.org/10.1016/j.chembiol.2020.06.004.

• Posfai, Dora, Steven P. Maher, Camille Roesch, Amélie Vantaux, Kayla Sylvester, Julie Péneau, Jean Popovici, Dennis E. Kyle, Benoît Witkowski, and Emily R. Derbyshire. “Plasmodium vivax Liver and Blood Stages Recruit the Druggable Host Membrane Channel Aquaporin-3.” Cell Chemical Biology 27, no. 6 (June 2020): 719-727.e5. https://doi.org/10.1016/j.chembiol.2020.03.009.

• Ganley, Jack G., Hannah K. D’Ambrosio, Meg Shieh, and Emily R. Derbyshire. “Coculturing of Mosquito-Microbiome Bacteria Promotes Heme Degradation in Elizabethkingia anophelis.” Chembiochem : A European Journal of Chemical Biology 21, no. 9 (May 2020): 1279–84. https://doi.org/10.1002/cbic.201900675.

• Lu, Kuan-Yi, and Emily R. Derbyshire. “Tafenoquine: A Step toward Malaria Elimination.” Biochemistry 59, no. 8 (March 2020): 911–20. https://doi.org/10.1021/acs.biochem.9b01105.

• Lu, Kuan-Yi, Baiyi Quan, Kayla Sylvester, Tamanna Srivastava, Michael C. Fitzgerald, and Emily R. Derbyshire. “Plasmodium chaperonin TRiC/CCT identified as a target of the antihistamine clemastine using parallel chemoproteomic strategy.” Proceedings of the National Academy of Sciences of the United States of America 117, no. 11 (March 2020): 5810–17. https://doi.org/10.1073/pnas.1913525117.

• Toro-Moreno, Maria, Kayla Sylvester, Tamanna Srivastava, Dora Posfai, and Emily R. Derbyshire. “RNA-Seq Analysis Illuminates the Early Stages of Plasmodium Liver Infection.” MBio 11, no. 1 (February 2020): e03234–e03219. https://doi.org/10.1128/mbio.03234-19.

• Toro-Moreno, Maria, and Emily R. Derbyshire. “It's about Time: Insights into the Modes of Action of Antimalarials.” Cell Chemical Biology 27, no. 2 (February 2020): 139–41. https://doi.org/10.1016/j.chembiol.2020.01.013.

• D’Ambrosio, Hannah K., and Emily R. Derbyshire. “Investigating the Role of Class I Adenylate-Forming Enzymes in Natural Product Biosynthesis.” ACS Chemical Biology 15, no. 1 (January 2020): 17–27. https://doi.org/10.1021/acschembio.9b00865.

• Ganley, Jack G., and Emily R. Derbyshire. “Linking Genes to Molecules in Eukaryotic Sources: An Endeavor to Expand Our Biosynthetic Repertoire.” Molecules (Basel, Switzerland) 25, no. 3 (January 2020): E625. https://doi.org/10.3390/molecules25030625.

• Raphemot, Rene, Maria Toro-Moreno, Kuan-Yi Lu, Dora Posfai, and Emily Rose Derbyshire. “Discovery of Druggable Host Factors Critical to Plasmodium Liver-Stage Infection.” Cell Chemical Biology 26, no. 9 (September 2019): 1253-1262.e5. https://doi.org/10.1016/j.chembiol.2019.05.011.