Greg Martin
BS, Biology, 2010. Iowa State University. Ames, IA, USA.
PhD, Biochemistry, 2018. Oregon Health & Science University. Portland, OR, USA.
Main research areas: Malaria vaccine design; malaria antibodies; cryo-electron microscopy; structural biology; computational biology; antimalarial resistance; membrane transporters.
Malaria has been a plague on humanity for thousands of years and is still today one of the deadliest infectious diseases, each year causing hundreds of million infections that result in hundreds of thousands of deaths worldwide. The malaria parasite, Plasmodium spp, has a remarkable ability to evolve resistance to drugs and to evade the human immune system. Thus, the world urgently needs better vaccines and antimalarials.
My lab is interested in both basic and applied aspects of malaria and malaria therapeutics, and is focused on two main projects: 1) how does the immune system respond to the malaria parasite, and how we can use these data to develop better vaccines? 2) how do membrane transporters contribute to antimalarial resistance?
We are structural biologists, meaning we aim to understand the 3D organization of biological macromolecules, like proteins and nucleic acids, in order to understand their function. Our primary tool is cryo-electron microscopy (cryo-EM), which allows us to generate atomic models of the 3-dimensional structure of our protein of interest. We use these data to understand, for instance, how a human antibody neutralizes Plasmodium and prevents infection, or how a mutation in a parasite transporter confers resistance to an antimalarial compound.
We then apply the principles of computational biology to rationally engineer protein-based malaria vaccines and test these in animal models for vaccine efficacy, with the long-term goal of testing improved malaria vaccine designs in humans in malaria-endemic regions, like sub-Saharan Africa and South America.
We also work with clinicians to apply our structural biology approach to ongoing clinical trials of malaria vaccines to provide a more complete picture of the variation in vaccine efficacy observed among trial participants, what are the key mediators of vaccine-mediated protection from malaria infection.
1. Martin GM, Patton BL, Shyng SL (2023). KATP channels in focus: progress toward a structural understanding of ligand regulation. Current Opinion in Structural Biology 79:102541. https://doi.org/10.1016/j.sbi.2023.102541
2. Martin GM, Torres JL, Pholcharee T, Oyen D, Flores-Garcia Y, Gibson G, Moskovitz R, Beutler N, Jung DD, Copps J, Lee WH, Gonzalez-Paez G, Emerling D, MacGill RS, Locke E, King CR, Zavala F,Wilson IA, Ward AB. Affinity-matured homotypic interactions induce spectrum of PfCSP-antibody structures that influence protection from malaria infection (2023). Nat Commun 14(1):4546. https://doi.org/10.1038/s41467-023-40151-x
3. Martin GM, Fernández-Quintero ML, Lee WH, Pholcharee T, Eshun-Wilson L, Liedl KR, Pancera M, Seder RA, Wilson IA, Ward AB (2023). Structural basis of epitope selectivity and potent protection from malaria by PfCSP antibody L9. Nat Commun 14(1):2815. https://doi.org/10.1038/s41467-023-38509-2
4. Martin GM*, Russell RA*, Mundsperger P, Harris S, Jovanoska L, Trajano LF, Schiffner T, Fabian K, Tolazzi M, Scarlatti G, McFarlane L, Cheeseman H, Aldon Y, Breemen M, Sliepen K, Katinger D, Kunert R, Sanders RW, Shattock R, Ward AB, Sattentau QJ. Profound structural conservation of chemically cross-linked HIV-1 envelope glycoprotein experimental vaccine antigens (2023). NPJ Vaccines 8(1):101. https://doi.org/10.1038/s41541-023-00696-w
5. Pholcharee T, Oyen D, Torres JL, Flores-Garcia Y, Martin GM, Gonzalez-Paez G, Emerling D, Volkmuth W, Locke E, King CR, Zavala F, Ward AB, Wilson IA. Diverse antibody responses to conserved structural motifs in Plasmodium falciparum circumsporozoite protein. J Mol Biol 432, 1048-1063 (2020). https://doi.org/10.1016/j.jmb.2019.12.029
6. Martin GM, Sung MW, Shyng SL. Pharmacological chaperones of ATP-sensitive potassium channels: Mechanistic insight from cryoEM structures (2020). Mol Cell Endocrinol 502, 110667 https://doi.org/10.1016/j.mce.2019.110667
7. Martin GM*, Sung MW*, Yang Z, Innes LM, Kandasamy B, Yoshioka C, Shyng SL (2019).
Mechanism of pharmacochaperoning in a mammalian KATP channel revealed by cryo-EM. eLife 8. https://doi.org/10.7554/eLife.46417
8. Martin GM, Kandasamy B, DiMaio F, Yoshioka C, Shyng SL. (2017). Anti-diabetic drug binding site in a mammalian KATP channel revealed by cryo-EM. eLife. October 24; 6. https://doi.org/10.7554/eLife.31054
9. Martin GM, Yoshioka C, Rex EA, Fay JF, Xie Q, Whorton MR, Chen JZ, Shyng SL. (2017). Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating. eLife. Jan 16; 6. https://doi.org/10.7554/eLife.24149
10. Martin GM*, Rex EA*, Devaraneni PK, Denton JS, Boodhansingh KE, DeLeon DD, Stanley CA, Shyng SL. (2016). Pharmacological correction of trafficking defects in ATP-sensitive potassium channels caused by sulfonylurea receptor 1 mutations. J Biol Chem. 291:21971-21983. https://doi.org/10.1074/jbc.M116.749366
11. Devaraneni PK, Martin GM, Olson EM, Zhou Q, Shyng SL. (2015). Structurally distinct ligands rescue biogenesis defects of the KATP channel complex via a converging mechanism. J Biol Chem. 290:7980-91. https://doi.org/10.1074/jbc.M114.634576
12. Saint-Martin C, Zhou Q, Martin GM, Vaury C, Leory G, Arnoux JB, de Lonlay P, Shyng SL, Bellanne-Chantelot C. (2015). Monoallelic ABCC8 mutations are a common cause of diazoxide-unresponsive diffuse form of congenital hyperinsulinism. Clin Genet. 87:448-454. https://doi.org/10.1111/cge.12428
13. Zhou Q, Chen PC, Devaraneni PK, Martin GM, Olson EM, Shyng SL. (2014). Carbamazepine inhibits ATP-sensitive potassium channel activity disrupting channel response to MgADP. Channels. 8:376-382. https://doi.org/10.4161/chan.29117
14. Martin GM, Chen PC, Devaraneni PK, Shyng SL. (2013). Pharmacological rescue of trafficking impaired ATP-sensitive potassium channels. Front Physiol. 4:386. https://doi.org/10.3389/fphys.2013.00386
* = authors contributed equally