Choukri Ben Mamoun, PhD
Professor of Medicine (Infectious Diseases) and of Microbial Pathogenesis; Affiliated Faculty, Yale Institute for Global Health
Research & Publications
Biography
News
Research Summary
Basic Research
Current research topics in the lab include:
- Identifying the molecular determinants of virulence of Babesia duncani and Babesia microti. We use mouse crosses, controlled infection and whole genome sequencing to identify specific host factors that play critical roles in Babesia virulence and pathogenesis.
- Understanding how Babesia parasites residing within human red blood cells deliver their secreted proteins to the mammalian host and how these proteins interact with the immune system of the host. Our lab discovered two main mechanisms by which Babesia parasites secrete their proteins: vesicular and non-vesicular mediated protein secretion. Our current efforts aim to identify the molecular signatures and machineries employed by these parasites to achieve successful delivery of their antigens into the host.
- Developing molecular tools for large scale functional analysis of parasite genomes.
- Using yeast as a model system to study the function and druggabality of pathogen targets.
Translational Medicine Program
Our translational medicine program builds upon the findings of our basic research efforts. Current investigations include:
- Antigen discovery and vaccine development with a specific focus on the human pathogens Babesia microti and Babesia duncani.
- Development of novel classes of antibabesial, antimalarial and antifungal drugs that target unique metabolic pathways essential for pathogen survival and virulence.
- Development of diagnostic assays for detection of active parasite infections.
Coauthors
Research Interests
Antifungal Agents; Babesiosis; Malaria; Opportunistic Infections; Protozoan Infections; Diagnostic Techniques and Procedures; Infectious Disease Medicine; Drug Discovery; Translational Research, Biomedical
Research Image
Malaria parasite in a human red blood cell
The image shows the final developmental stage (schizont) of the human malaria parasite Plasmodium falciparum during its intra-erythrocytic life cycle in human red blood cells.
Selected Publications
- Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microtiChand M, Choi J, Pal A, Singh P, Kumari V, Thekkiniath J, Gagnon J, Timalsina S, Gaur G, Williams S, Ledizet M, Mamoun C. Epitope profiling of monoclonal antibodies to the immunodominant antigen BmGPI12 of the human pathogen Babesia microti Frontiers In Cellular And Infection Microbiology 2022, 12: 1039197. PMID: 36506011, PMCID: PMC9732259, DOI: 10.3389/fcimb.2022.1039197.
- Babesia duncani in Culture and in Mouse (ICIM) Model for the Advancement of Babesia Biology, Pathogenesis, and Therapy.Kumari V, Pal A, Singh P, Mamoun C. Babesia duncani in Culture and in Mouse (ICIM) Model for the Advancement of Babesia Biology, Pathogenesis, and Therapy. Bio-protocol 2022, 12 PMID: 36620533, PMCID: PMC9795036, DOI: 10.21769/bioprotoc.4549.
- High-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal developmentGihaz S, Gareiss P, Choi JY, Renard I, Pal AC, Surovsteva Y, Chiu JE, Thekkiniath J, Plummer M, Hungerford W, Montgomery ML, Hosford A, Adams EM, Lightfoot JD, Fox D, Ojo KK, Staker BL, Fuller K, Ben Mamoun C. High-resolution crystal structure and chemical screening reveal pantothenate kinase as a new target for antifungal development Structure 2022, 30: 1494-1507.e6. PMID: 36167065, PMCID: PMC10042587, DOI: 10.1016/j.str.2022.09.001.
- Specific and Sensitive Diagnosis of Babesia microti Active Infection Using Monoclonal Antibodies to the Immunodominant Antigen BmGPI12Gagnon J, Timalsina S, Choi JY, Chand M, Singh P, Lamba P, Gaur G, Pal AC, Mootien S, Marcos LA, Mamoun C, Ledizet M. Specific and Sensitive Diagnosis of Babesia microti Active Infection Using Monoclonal Antibodies to the Immunodominant Antigen BmGPI12 Journal Of Clinical Microbiology 2022, 60: e00925-22. PMID: 36040206, PMCID: PMC9491189, DOI: 10.1128/jcm.00925-22.
- An Alternative Culture Medium for Continuous In Vitro Propagation of the Human Pathogen Babesia duncani in Human ErythrocytesSingh P, Pal AC, Mamoun CB. An Alternative Culture Medium for Continuous In Vitro Propagation of the Human Pathogen Babesia duncani in Human Erythrocytes Pathogens 2022, 11: 599. PMID: 35631120, PMCID: PMC9146245, DOI: 10.3390/pathogens11050599.
- Babesia duncani as a Model Organism to Study the Development, Virulence, and Drug Susceptibility of Intraerythrocytic Parasites In Vitro and In Vivo.Pal AC, Renard I, Singh P, Vydyam P, Chiu JE, Pou S, Winter RW, Dodean R, Frueh L, Nilsen AC, Riscoe MK, Doggett JS, Ben Mamoun C. Babesia duncani as a Model Organism to Study the Development, Virulence, and Drug Susceptibility of Intraerythrocytic Parasites In Vitro and In Vivo. The Journal Of Infectious Diseases 2022, 226: 1267-1275. PMID: 35512141, DOI: 10.1093/infdis/jiac181.
- Redesigning therapies for pantothenate kinase–associated neurodegenerationMunshi MI, Yao SJ, Mamoun C. Redesigning therapies for pantothenate kinase–associated neurodegeneration Journal Of Biological Chemistry 2022, 298: 101577. PMID: 35041826, PMCID: PMC8861153, DOI: 10.1016/j.jbc.2022.101577.
- Treatment of Human Babesiosis: Then and Now.Renard I, Ben Mamoun C. Treatment of Human Babesiosis: Then and Now. Pathogens (Basel, Switzerland) 2021, 10 PMID: 34578153, PMCID: PMC8469882, DOI: 10.3390/pathogens10091120.
- Effective Therapy Targeting Cytochrome bc1 Prevents Babesia Erythrocytic Development and Protects from Lethal InfectionChiu JE, Renard I, Pal AC, Singh P, Vydyam P, Thekkiniath J, Kumar M, Gihaz S, Pou S, Winter RW, Dodean R, Frueh L, Nilsen AC, Riscoe MK, Doggett JS, Mamoun C. Effective Therapy Targeting Cytochrome bc1 Prevents Babesia Erythrocytic Development and Protects from Lethal Infection Antimicrobial Agents And Chemotherapy 2021, 65: e00662-21. PMID: 34152821, PMCID: PMC8370247, DOI: 10.1128/aac.00662-21.
- Cytochrome b Drug Resistance Mutation Decreases Babesia Fitness in the Tick Stages But Not the Mammalian Erythrocytic Cycle.Chiu JE, Renard I, George S, Pal A, Alday PH, Narasimhan S, Riscoe MK, Doggett JS, Ben Mamoun C. Cytochrome b Drug Resistance Mutation Decreases Babesia Fitness in the Tick Stages But Not the Mammalian Erythrocytic Cycle. The Journal Of Infectious Diseases 2021, 225: 135-145. PMID: 34139755, PMCID: PMC8730496, DOI: 10.1093/infdis/jiab321.
- Tick extracellular vesicles enable arthropod feeding and promote distinct outcomes of bacterial infectionOliva Chávez AS, Wang X, Marnin L, Archer NK, Hammond HL, Carroll EEM, Shaw DK, Tully BG, Buskirk AD, Ford SL, Butler LR, Shahi P, Morozova K, Clement CC, Lawres L, Neal A, Mamoun CB, Mason KL, Hobbs BE, Scoles GA, Barry EM, Sonenshine DE, Pal U, Valenzuela JG, Sztein MB, Pasetti MF, Levin ML, Kotsyfakis M, Jay SM, Huntley JF, Miller LS, Santambrogio L, Pedra JHF. Tick extracellular vesicles enable arthropod feeding and promote distinct outcomes of bacterial infection Nature Communications 2021, 12: 3696. PMID: 34140472, PMCID: PMC8211691, DOI: 10.1038/s41467-021-23900-8.
- Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria.Raj DK, Das Mohapatra A, Jnawali A, Zuromski J, Jha A, Cham-Kpu G, Sherman B, Rudlaff RM, Nixon CE, Hilton N, Oleinikov AV, Chesnokov O, Merritt J, Pond-Tor S, Burns L, Jolly G, Ben Mamoun C, Kabyemela E, Muehlenbachs A, Lambert L, Orr-Gonzalez S, Gnädig NF, Fidock DA, Park S, Dvorin JD, Pardi N, Weissman D, Mui BL, Tam YK, Friedman JF, Fried M, Duffy PE, Kurtis JD. Anti-PfGARP activates programmed cell death of parasites and reduces severe malaria. Nature 2020, 582: 104-108. PMID: 32427965, PMCID: PMC7372601, DOI: 10.1038/s41586-020-2220-1.
- An improved and highly selective fluorescence assay for measuring phosphatidylserine decarboxylase activity Fluorescence detection of PS decarboxylase activityChoi JY, Black R, Lee H, Di Giovanni J, Murphy RC, Ben Mamoun C, Voelker DR. An improved and highly selective fluorescence assay for measuring phosphatidylserine decarboxylase activity Fluorescence detection of PS decarboxylase activity Journal Of Biological Chemistry 2020, 295: 9211-9222. PMID: 32430397, PMCID: PMC7335775, DOI: 10.1074/jbc.ra120.013421.
- Palmitoylated Proteins in Plasmodium falciparum‐Infected Erythrocytes: Investigation with Click Chemistry and Metabolic LabelingKilian N, Zhang Y, LaMonica L, Hooker G, Toomre D, Mamoun CB, Ernst AM. Palmitoylated Proteins in Plasmodium falciparum‐Infected Erythrocytes: Investigation with Click Chemistry and Metabolic Labeling BioEssays 2020, 42: e1900145. PMID: 32342554, DOI: 10.1002/bies.201900145.
- Evidence for vesicle-mediated antigen export by the human pathogen Babesia microtiThekkiniath J, Kilian N, Lawres L, Gewirtz MA, Graham MM, Liu X, Ledizet M, Mamoun C. Evidence for vesicle-mediated antigen export by the human pathogen Babesia microti Life Science Alliance 2019, 2: e201900382. PMID: 31196872, PMCID: PMC6572159, DOI: 10.26508/lsa.201900382.
- Comparative 3D genome organization in apicomplexan parasitesBunnik EM, Venkat A, Shao J, McGovern KE, Batugedara G, Worth D, Prudhomme J, Lapp SA, Andolina C, Ross LS, Lawres L, Brady D, Sinnis P, Nosten F, Fidock DA, Wilson EH, Tewari R, Galinski MR, Ben Mamoun C, Ay F, Le Roch KG. Comparative 3D genome organization in apicomplexan parasites Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 3183-3192. PMID: 30723152, PMCID: PMC6386730, DOI: 10.1073/pnas.1810815116.
- Establishment of a continuous in vitro culture of Babesia duncani in human erythrocytes reveals unusually high tolerance to recommended therapiesAbraham A, Brasov I, Thekkiniath J, Kilian N, Lawres L, Gao R, DeBus K, He L, Yu X, Zhu G, Graham MM, Liu X, Molestina R, Ben Mamoun C. Establishment of a continuous in vitro culture of Babesia duncani in human erythrocytes reveals unusually high tolerance to recommended therapies Journal Of Biological Chemistry 2018, 293: 19974-19981. PMID: 30463941, PMCID: PMC6311517, DOI: 10.1074/jbc.ac118.005771.
- BmGPAC, an Antigen Capture Assay for Detection of Active Babesia microti InfectionThekkiniath J, Mootien S, Lawres L, Perrin BA, Gewirtz M, Krause PJ, Williams S, Doggett J, Ledizet M, Mamoun C. BmGPAC, an Antigen Capture Assay for Detection of Active Babesia microti Infection Journal Of Clinical Microbiology 2018, 56: e00067-18. PMID: 30093394, PMCID: PMC6156295, DOI: 10.1128/jcm.00067-18.
- Antimalarial Properties of Simplified Kalihinol AnaloguesDaub ME, Prudhomme J, Mamoun C, Le Roch KG, Vanderwal CD. Antimalarial Properties of Simplified Kalihinol Analogues ACS Medicinal Chemistry Letters 2017, 8: 355-360. PMID: 28337330, PMCID: PMC5346982, DOI: 10.1021/acsmedchemlett.7b00013.
- Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and BeyondVan Voorhis WC, Adams JH, Adelfio R, Ahyong V, Akabas MH, Alano P, Alday A, Resto Y, Alsibaee A, Alzualde A, Andrews KT, Avery SV, Avery VM, Ayong L, Baker M, Baker S, Mamoun C, Bhatia S, Bickle Q, Bounaadja L, Bowling T, Bosch J, Boucher LE, Boyom FF, Brea J, Brennan M, Burton A, Caffrey CR, Camarda G, Carrasquilla M, Carter D, Cassera M, Cheng K, Chindaudomsate W, Chubb A, Colon BL, Colón-López DD, Corbett Y, Crowther GJ, Cowan N, D’Alessandro S, Le Dang N, Delves M, DeRisi JL, Du AY, Duffy S, El-Sayed S, Ferdig MT, Robledo J, Fidock DA, Florent I, Fokou PV, Galstian A, Gamo FJ, Gokool S, Gold B, Golub T, Goldgof GM, Guha R, Guiguemde WA, Gural N, Guy RK, Hansen MA, Hanson KK, Hemphill A, van Huijsduijnen R, Horii T, Horrocks P, Hughes TB, Huston C, Igarashi I, Ingram-Sieber K, Itoe MA, Jadhav A, Jensen A, Jensen LT, Jiang RH, Kaiser A, Keiser J, Ketas T, Kicka S, Kim S, Kirk K, Kumar VP, Kyle DE, Lafuente MJ, Landfear S, Lee N, Lee S, Lehane AM, Li F, Little D, Liu L, Llinás M, Loza MI, Lubar A, Lucantoni L, Lucet I, Maes L, Mancama D, Mansour NR, March S, McGowan S, Vera I, Meister S, Mercer L, Mestres J, Mfopa AN, Misra RN, Moon S, Moore JP, da Costa F, Müller J, Muriana A, Hewitt S, Nare B, Nathan C, Narraidoo N, Nawaratna S, Ojo KK, Ortiz D, Panic G, Papadatos G, Parapini S, Patra K, Pham N, Prats S, Plouffe DM, Poulsen SA, Pradhan A, Quevedo C, Quinn RJ, Rice CA, Rizk M, Ruecker A, St. Onge R, Ferreira R, Samra J, Robinett NG, Schlecht U, Schmitt M, Villela F, Silvestrini F, Sinden R, Smith DA, Soldati T, Spitzmüller A, Stamm SM, Sullivan DJ, Sullivan W, Suresh S, Suzuki BM, Suzuki Y, Swamidass SJ, Taramelli D, Tchokouaha LR, Theron A, Thomas D, Tonissen KF, Townson S, Tripathi AK, Trofimov V, Udenze KO, Ullah I, Vallieres C, Vigil E, Vinetz JM, Vinh P, Vu H, Watanabe NA, Weatherby K, White PM, Wilks AF, Winzeler EA, Wojcik E, Wree M, Wu W, Yokoyama N, Zollo PH, Abla N, Blasco B, Burrows J, Laleu B, Leroy D, Spangenberg T, Wells T, Willis PA. Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond PLOS Pathogens 2016, 12: e1005763. PMID: 27467575, PMCID: PMC4965013, DOI: 10.1371/journal.ppat.1005763.
- Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquoneLawres LA, Garg A, Kumar V, Bruzual I, Forquer IP, Renard I, Virji AZ, Boulard P, Rodriguez EX, Allen AJ, Pou S, Wegmann KW, Winter RW, Nilsen A, Mao J, Preston DA, Belperron AA, Bockenstedt LK, Hinrichs DJ, Riscoe MK, Doggett JS, Mamoun C. Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone Journal Of Experimental Medicine 2016, 213: 1307-1318. PMID: 27270894, PMCID: PMC4925016, DOI: 10.1084/jem.20151519.
- Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmissionBobenchik AM, Witola WH, Augagneur Y, Lochlainn L, Garg A, Pachikara N, Choi JY, Zhao YO, Usmani-Brown S, Lee A, Adjalley SH, Samanta S, Fidock DA, Voelker DR, Fikrig E, Mamoun C. Plasmodium falciparum phosphoethanolamine methyltransferase is essential for malaria transmission Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 18262-18267. PMID: 24145416, PMCID: PMC3831454, DOI: 10.1073/pnas.1313965110.
- Sequencing of the smallest Apicomplexan genome from the human pathogen Babesia microtiCornillot E, Hadj-Kaddour K, Dassouli A, Noel B, Ranwez V, Vacherie B, Augagneur Y, Brès V, Duclos A, Randazzo S, Carcy B, Debierre-Grockiego F, Delbecq S, Moubri-Ménage K, Shams-Eldin H, Usmani-Brown S, Bringaud F, Wincker P, Vivarès CP, Schwarz RT, Schetters TP, Krause PJ, Gorenflot A, Berry V, Barbe V, Mamoun C. Sequencing of the smallest Apicomplexan genome from the human pathogen Babesia microti Nucleic Acids Research 2012, 40: 9102-9114. PMID: 22833609, PMCID: PMC3467087, DOI: 10.1093/nar/gks700.
- Phosphoethanolamine methyltransferases in phosphocholine biosynthesis: functions and potential for antiparasite therapyBobenchik AM, Augagneur Y, Hao B, Hoch JC, Mamoun C. Phosphoethanolamine methyltransferases in phosphocholine biosynthesis: functions and potential for antiparasite therapy FEMS Microbiology Reviews 2011, 35: 609-619. PMID: 21303393, PMCID: PMC4107886, DOI: 10.1111/j.1574-6976.2011.00267.x.
- Disruption of the Plasmodium falciparum PfPMT Gene Results in a Complete Loss of Phosphatidylcholine Biosynthesis via the Serine-Decarboxylase-Phosphoethanolamine-Methyltransferase Pathway and Severe Growth and Survival Defects*Witola WH, El Bissati K, Pessi G, Xie C, Roepe PD, Mamoun CB. Disruption of the Plasmodium falciparum PfPMT Gene Results in a Complete Loss of Phosphatidylcholine Biosynthesis via the Serine-Decarboxylase-Phosphoethanolamine-Methyltransferase Pathway and Severe Growth and Survival Defects* Journal Of Biological Chemistry 2008, 283: 27636-27643. PMID: 18694927, PMCID: PMC2562060, DOI: 10.1074/jbc.m804360200.
- Genetic evidence for the essential role of PfNT1 in the transport and utilization of xanthine, guanine, guanosine and adenine by Plasmodium falciparumBissati K, Downie MJ, Kim SK, Horowitz M, Carter N, Ullman B, Mamoun C. Genetic evidence for the essential role of PfNT1 in the transport and utilization of xanthine, guanine, guanosine and adenine by Plasmodium falciparum Molecular And Biochemical Parasitology 2008, 161: 130-139. PMID: 18639591, PMCID: PMC2612043, DOI: 10.1016/j.molbiopara.2008.06.012.
- The plasma membrane permease PfNT1 is essential for purine salvage in the human malaria parasite Plasmodium falciparumBissati K, Zufferey R, Witola WH, Carter NS, Ullman B, Mamoun C. The plasma membrane permease PfNT1 is essential for purine salvage in the human malaria parasite Plasmodium falciparum Proceedings Of The National Academy Of Sciences Of The United States Of America 2006, 103: 9286-9291. PMID: 16751273, PMCID: PMC1482602, DOI: 10.1073/pnas.0602590103.
- A pathway for phosphatidylcholine biosynthesis in Plasmodium falciparum involving phosphoethanolamine methylationPessi G, Kociubinski G, Mamoun CB. A pathway for phosphatidylcholine biosynthesis in Plasmodium falciparum involving phosphoethanolamine methylation Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 6206-6211. PMID: 15073329, PMCID: PMC395947, DOI: 10.1073/pnas.0307742101.
- A set of independent selectable markers for transfection of the human malaria parasite Plasmodium falciparumMamoun C, Gluzman I, Goyard S, Beverley S, Goldberg D. A set of independent selectable markers for transfection of the human malaria parasite Plasmodium falciparum Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8716-8720. PMID: 10411941, PMCID: PMC17582, DOI: 10.1073/pnas.96.15.8716.