Profile
Manuel Fierro Calisto
Genetics and Biochemistry
Assistant Professor
864-656-4696
Life Sciences Building 60B [Lab]
Educational Background
Post Doctorate, Molecular Parasitology, Iowa State University, 2020-2024
Ph.D., Cell Biology, University of Georgia, 2020
B.S., Cell Biology, University of Georgia, 2014
Profile/About Me
I was born in Quito, Ecuador and moved to Georgia at a young age. I grew an interest in cells and their fascinating biology during high school and went to the University of Georgia where I received a Bachelor's in Cell Biology. During my studies, I took an interest in protozoan parasites and decided to pursue a PhD at the University of Georgia to study the process of host-cell egress in the deadliest of the malaria-causing parasites, Plasmodium falciparum. I continued my postdoctoral training at Iowa State University to understand the process of protein export and host-cell subversion in Plasmodium. I joined the Department of Genetics and Biochemistry and the Eukaryotic Pathogens Innovation Center in 2024 as an assistant professor.
Research Interests
My lab is interested in studying the biology of Plasmodium to identify novel points of attack that can lead to novel antimalarial or vaccine development. As such, we use a wide range of functional and reverse genetic approaches and employ novel molecular tool development to accomplish these goals. Specifically, I am interested in understanding the host-pathogen interactions present during blood-stage infection of Plasmodium falciparum by characterizing the essential process of host-cell remodeling.
In order to survive within red blood cells (RBCs), P. falciparum relies on an intricate system of protein export and secretion that remodels its host for survival. During invasion, Plasmodium parasites invaginate the host membrane and form a vacuolar niche called the Parasitophorous Vacuole (PV) which becomes the main interphase of host-pathogen interactions. Upon formation, the membrane of the PV (PVM) forms a physical barrier and requires a mechanism to mediate exchange of nutrients and translocation of proteins into the RBC. Solute permeation across the PVM is mediated by a nutrient-permeable channel formed by a pore-forming protein called EXP2. In malaria parasites, this nutrient pore has been additionally functionalized by the AAA+ chaperone HSP101 and flange-like adaptor PTEX150 to form the Plasmodium Translocon of EXported proteins (PTEX). My lab seeks to understand the mechanism used to insert EXP2 into the PV membrane in order to carry out both protein export and solute/nutrient exchange.
As protein export is required for parasite survival within the vertebrate host, my lab also seeks to characterize the exportome of malaria parasites using proximity labeling and quantitative mass spectrometry. This will help identify new candidates that can be used for novel vaccine development against this deadly parasite.
Selected Publications
Anaguano D, Adewale-Fasoro O, Vick GW, Yanik S, Blauwkamp J, Fierro MA, Absalon S, Srinivasan P, Muralidharan V. Plasmodium RON11 triggers biogenesis of the merozoite rhoptry pair and is essential for erythrocyte invasion. PLoS Biol. 2024 Sep;22(9):e3002801. doi: 10.1371/journal.pbio.3002801. eCollection 2024 Sep. PubMed PMID: 39292724; PubMed Central PMCID: PMC11441699.
Fierro MA, Muheljic A, Sha J, Wohlschlegel J, Beck JR.2024.PEXEL is a proteolytic maturation site for both exported and non-exported Plasmodium proteins. mSphere9:e00393-23.https://doi.org/10.1128/msphere.00393-23
Fierro MA, Hussain T, Campin LJ, Beck JR. Knock-sideways by inducible ER retrieval enables a unique approach for studying Plasmodium-secreted proteins. Proc Natl Acad Sci U S A. 2023 Aug 15;120(33):e2308676120. doi: 10.1073/pnas.2308676120. Epub 2023 Aug 8. Erratum in: Proc Natl Acad Sci U S A. 2024 Aug 6;121(32):e2413670121. doi: 10.1073/pnas.2413670121.
Hussain T, Linera-Gonzalez J, Beck JM, Fierro MA, Mair GR, Smith RC, Beck JR,2022.The PTEX Pore Component EXP2 Is Important for Intrahepatic Development during the Plasmodium Liver Stage. mBio13:e03096-22.https://doi.org/10.1128/mbio.03096-22
Fierro MA, Asady B, Brooks CF, Cobb DW, Villegas A, Moreno SNJ, Muralidharan V. An Endoplasmic Reticulum CREC Family Protein Regulates the Egress Proteolytic Cascade in Malaria Parasites. mBio. 2020 Feb 25;11(1). doi: 10.1128/mBio.03078-19. PubMed PMID: 32098818; PubMed Central PMCID: PMC7042697.
Kudyba HM, Cobb DW, Fierro MA, Florentin A, Ljolje D, Singh B, Lucchi NW, Muralidharan V. The endoplasmic reticulum chaperone PfGRP170 is essential for asexual development and is linked to stress response in malaria parasites. Cell Microbiol. 2019 Sep;21(9):e13042. doi: 10.1111/cmi.13042. Epub 2019 Jun 6. PubMed PMID: 31087747; PubMed Central PMCID: PMC6699899.
Florentin A, Cobb DW, Fishburn JD, Cipriano MJ, Kim PS, Fierro MA, Striepen B, Muralidharan V. PfClpC Is an Essential Clp Chaperone Required for Plastid Integrity and Clp Protease Stability in Plasmodium falciparum. Cell Rep. 2017 Nov 14;21(7):1746-1756. doi: 10.1016/j.celrep.2017.10.081. PubMed PMID: 29141210; PubMed Central PMCID: PMC5726808.
Cobb DW, Florentin A, Fierro MA, Krakowiak M, Moore JM, Muralidharan V. The Exported Chaperone PfHsp70x Is Dispensable for the Plasmodium falciparum Intraerythrocytic Life Cycle. mSphere. 2017 Sep-Oct;2(5). doi: 10.1128/mSphere.00363-17. eCollection 2017 Sep-Oct. PubMed PMID: 28959740; PubMed Central PMCID: PMC5615134.
