Jeffrey Dvorin
· Associate ProfessorVerifiedHarvard University · Strategy
Active 2001–2026
About
Jeffrey Dvorin completed his MD/PhD at the University of Pennsylvania and did his residency at Children's Hospital of Philadelphia. He then moved to Boston Children's Hospital at Harvard Medical School for his fellowship in Pediatric Infectious Diseases. After finishing his clinical fellowship, he completed a postdoctoral fellowship in the laboratory of Manoj Duraisingh in the Department of Immunology and Infectious Diseases at the Harvard School of Public Health, where he studied the molecular pathogenesis of the human malaria parasite Plasmodium falciparum. He joined the faculty at Boston Children's Hospital and Harvard Medical School in 2010 and started his independent laboratory in 2011. Since starting his laboratory, Jeffrey Dvorin has applied novel techniques to understand the critical cell biology of the Plasmodium falciparum parasite. In addition to his research, he remains clinically active in the Division of Infectious Diseases at Boston Children's Hospital.
Research topics
- Immunology
- Biology
- Virology
- Computer Science
- Genetics
- Anatomy
- Evolutionary biology
- Physics
- Veterinary medicine
- Medicine
- Optics
- Computational biology
- Pathology
- Cell biology
Selected publications
bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-08
articleOpen accessSenior authorCorrespondingAbstract The apical polar ring (APR) is a defining cytoskeletal structure in apicomplexan parasites, critical for parasite morphology and host cell invasion. However, its molecular composition and function remain elusive in Plasmodium falciparum . Here, we identify and characterize PfAPR1 as an APR-resident protein. Conditional knockout of PfAPR1 reveals its essential role in asexual replication. Using iterative ultrastructure expansion microscopy (iU-ExM), we show that PfAPR1 predominantly localizes to the basal APR ring. Loss of PfAPR1 causes defects in daughter cell segmentation and subpellicular microtubules organization, while IMC formation and apical polarity are largely preserved. PfAPR1-KO parasites contact host red blood cells but fail to form a tight junction, resulting in a complete block in invasion. Using PfAPR1 as molecular bait, we identify additional APR proteins and delineate APR biogenesis with U-ExM. These findings define the molecular architecture and function of the APR in P. falciparum, highlighting it as a promising antimalarial target.
Nature Communications · 2026-05-07
articleOpen accessArtemisinin combination therapies are central to malaria control, but their efficacy is threatened by the emergence of resistant Plasmodium falciparum strains. While the role of Pfkelch13 mutations is well established, mutations in Pfcoronin have also been implicated in treatment failure, revealing layers of resistance complexity. Here, we define the cellular mechanism of Pfcoronin‑mediated artemisinin resistance. PfCoronin interacts with PfActin and localizes to the parasite plasma membrane, the digestive vacuole membrane, and small vesicles containing host cell material. Mutations in PfCoronin disrupt its localization and perturb PfActin homeostasis, altering the distribution of ring‑stage morphologies, including a reduced proportion of parasites adopting the cup‑shaped architecture. These changes are associated with decreased uptake of host cell contents by ring‑stage P. falciparum. Consistent with prior work on Pfkelch13 mutants, reduced hemoglobin uptake emerges as a feature of Pfcoronin‑mediated resistance. Although PfKelch13 and PfCoronin reside in distinct compartments and show no evidence of direct interaction, both influence endocytic access to hemoglobin. We propose that reduced hemoglobin uptake in ring‑stage parasites limits heme‑dependent activation of artemisinin and thus reduces its cytocidal activity. Our findings demonstrate that Pfcoronin mutations reduce endocytosis and modulate artemisinin susceptibility-highlighting how non‑essential, temporally restricted proteins can shape drug response and resistance.
Science Advances · 2026-02-18
articleOpen accessSenior authorCorrespondingAsexual reproduction of malaria parasites requires the basal complex, the equivalent of a eukaryotic contractile ring. Despite its central role, basal complex biogenesis remains largely unknown. Here, we use expansion microscopy and DNA points accumulation for imaging in nanoscale topography to investigate three transmembrane basal complex proteins in Plasmodium falciparum —basal complex transmembrane protein 1 (BTP1), BTP2, and basolateral expansion boundary (BLEB). Parasites lacking BTP2 are still enveloped by membranes but fail to separate from each other, resulting in multiorganellar mutants. We isolate the defect to a specific step during basal complex development and demonstrate that the contractile ability remains intact. By revisiting BLEB, we identify a distinct plasma membrane region that is excluded from daughter cells and associated with the basal complex. Integrating these findings, we propose a three-step model for basal complex biogenesis that highlights the specific role of BTP2 and suggests a role for the BLEB-associated membrane. This study offers a mechanistic framework for how multiple daughter cells are formed simultaneously and highlights the importance of transmembrane proteins for cell division.
The apical polar ring is essential during the blood stage of Plasmodium falciparum
Nature Microbiology · 2026-05-14
articleOpen accessSenior authorThe apical polar ring (APR) is a defining cytoskeletal structure in apicomplexan parasites, critical for parasite morphology and host cell invasion. However, its molecular composition and function remain elusive in Plasmodium falciparum. Here we identify and characterize PfAPR3 as an APR-resident protein. Conditional knockout of PfAPR3 reveals its essential role in asexual replication. PfAPR3-knockout parasites contact host red blood cells but fail to form a tight junction, resulting in a complete block in invasion. Using PfAPR3 as bait, we identify three additional APR proteins (PfAPR4, PfCHAKRA and PfAPR5) and delineate APR biogenesis with ultrastructure expansion microscopy. Unlike PfAPR3, PfCHAKRA is critical for cytoskeletal network organization. Iterative ultrastructure expansion microscopy further shows PfCHAKRA at the basal APR until mid-schizogony, with PfAPR3 exhibiting dual apical-basal ring localization during schizogony. These findings define the molecular architecture and function of the APR in P. falciparum and have implications for understanding parasite host cell infection.
Communications Biology · 2025-02-07 · 7 citations
articleOpen accessSenior authorPlasmodium species replicate via schizogony, which involves asynchronous nuclear divisions followed by semi-synchronous segmentation and cytokinesis. Successful segmentation requires a double-membranous structure known as the inner membrane complex (IMC). Here we demonstrate that PfFBXO1 (PF3D7_0619700) is critical for both asexual segmentation and gametocyte maturation. In Toxoplasma gondii, the FBXO1 homolog, TgFBXO1, is essential for the development of the daughter cell scaffold and a component of the daughter cell IMC. We demonstrate PfFBXO1 forming a similar IMC initiation scaffold near the apical region of developing merozoites and unilaterally positioned in gametocytes of P. falciparum. While PfFBXO1 initially localizes to the apical region of dividing parasites, it displays an IMC-like localization as segmentation progresses. Similarly, PfFBXO1 localizes to the IMC region in gametocytes. Following inducible knockout of PfFBXO1, parasites undergo abnormal segmentation and karyokinesis, generating inviable daughters. PfFBXO1-deficient gametocytes are abnormally shaped and fail to fully mature. Proteomic analysis identified PfSKP1 as one of PfBXO1's stable interacting partners, while other major proteins included multiple IMC pellicle and membrane proteins. We hypothesize that PfFBXO1 is necessary for IMC biogenesis, chromosomal maintenance, vesicular transport, and ubiquitin-mediated translational regulation of proteins in both sexual and asexual stages of P. falciparum.
bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-08 · 1 citations
preprintOpen accessSummary Artemisinin-based therapies are central to malaria treatment, but their efficacy is threatened by the emergence of resistant Plasmodium falciparum strains. While the role of Pfkelch13 mutations in clinical resistance is well established, recent reports from Africa implicate Pfcoronin mutations in treatment failure, adding to the complexity of resistance mechanisms. Here, we show that Pf Coronin, a non-essential actin regulator active during the ring-stage, facilitates efficient hemoglobin uptake. We demonstrate that resistance-associated Pfcoronin mutations disrupt Pf Coronin’s interaction with Pf Actin and its ring-stage localization, leading to impaired endocytosis and reduced hemoglobin acquisition. Pf Coronin and Pf Kelch13 function in distinct cellular regions; mutations in both converge to limit heme availability and artemisinin activation. Although Pf Coronin is dispensable for parasite viability, our findings demonstrate that Pfcoronin mutations reduce endocytosis and modulate artemisinin susceptibility during the clinically relevant ring stage—highlighting how non-essential, temporally restricted proteins can shape antimalarial drug response and resistance.
Malaria Cytoskeletal Proteins Require Alveolin–Alveolin Interactions for Differential Localization
Cellular Microbiology · 2025-01-01 · 2 citations
articleOpen accessSenior authorCorrespondingThe alveolins are a family of intermediate filament‐like proteins that form cytoskeletal structures in both free‐living and parasitic members of the alveolate kingdom. Despite their important functions, the alveolins’ biochemical properties and organizing principles are still poorly understood. Here, we characterize four alveolins of Plasmodium falciparum , the deadliest malaria parasite, to understand how alveolin domains mediate protein–protein interactions and highly specific recruitment to substructures of the cytoskeleton. Unexpectedly, we uncover variable dependence on alveolin domains for each substructure rather than an overarching mechanism. While Pf IMC1e requires 1f to be sequentially recruited to the basal complex, Pf IMC1c and Pf IMC1g do not require interactions with each other to localize properly to the inner membrane complex. Moreover, alveolin domains are not interchangeable—they contain unique signatures for specialized localization. Finally, we identify a region outside the alveolin domain of Pf IMC1e that is important for basal complex recruitment. These results provide direct evidence that alveolin domains mediate both alveolin–alveolin interactions and compartment‐specific localization.
mBio · 2024-04-02 · 7 citations
articleOpen accessSenior authorABSTRACT Condensin I is a pentameric complex that regulates the mitotic chromosome assembly in eukaryotes. The kleisin subunit CAP-H of the condensin I complex acts as a linchpin to maintain the structural integrity and loading of this complex on mitotic chromosomes. This complex is present in all eukaryotes and has recently been identified in Plasmodium spp. However, how this complex is assembled and whether the kleisin subunit is critical for this complex in these parasites are yet to be explored. To examine the role of PfCAP-H during cell division within erythrocytes, we generated an inducible PfCAP-H knockout parasite. We find that PfCAP-H is dynamically expressed during mitosis with the peak expression at the metaphase plate. PfCAP-H interacts with PfCAP-G and is a non-SMC member of the condensin I complex. Notably, the absence of PfCAP-H does not alter the expression of PfCAP-G but affects its localization at the mitotic chromosomes. While mitotic spindle assembly is intact in PfCAP-H-deficient parasites, duplicated centrosomes remain clustered over the mass of unsegmented nuclei with failed karyokinesis. This failure leads to the formation of an abnormal nuclear mass, while cytokinesis occurs normally. Altogether, our data suggest that PfCAP-H plays a crucial role in maintaining the structural integrity of the condensin I complex on the mitotic chromosomes and is essential for the asexual development of malarial parasites. IMPORTANCE Mitosis is a fundamental process for Plasmodium parasites, which plays a vital role in their survival within two distinct hosts—human and Anopheles mosquitoes. Despite its great significance, our comprehension of mitosis and its regulation remains limited. In eukaryotes, mitosis is regulated by one of the pivotal complexes known as condensin complexes. The condensin complexes are responsible for chromosome condensation, ensuring the faithful distribution of genetic material to daughter cells. While condensin complexes have recently been identified in Plasmodium spp., our understanding of how this complex is assembled and its precise functions during the blood stage development of Plasmodium falciparum remains largely unexplored. In this study, we investigate the role of a central protein, PfCAP-H, during the blood stage development of P. falciparum . Our findings reveal that PfCAP-H is essential and plays a pivotal role in upholding the structure of condensin I and facilitating karyokinesis.
bioRxiv (Cold Spring Harbor Laboratory) · 2024-02-29
preprintOpen accessSenior authorCorrespondingAbstract Condensin I is a pentameric complex that regulates the mitotic chromosome assembly in eukaryotes. The kleisin subunit CAP-H of the condensin I complex acts as a linchpin to maintain the structural integrity and loading of this complex on mitotic chromosomes. This complex is present in all eukaryotes and has recently been identified in Plasmodium spp . However, how this complex is assembled and whether the kleisin subunit is critical for this complex in these parasites is yet to be explored. To examine the role of PfCAP-H during cell division within erythrocytes, we generated an inducible PfCAP-H knockout parasite. We find that PfCAP-H is dynamically expressed during mitosis with the peak expression at the metaphase plate. PfCAP-H interacts with PfCAP-G and is a non-SMC member of the condensin I complex. Notably, the absence of PfCAP-H does not alter the expression of PfCAP-G but affects its localization at the mitotic chromosomes. While mitotic spindle assembly is intact in PfCAP-H deficient parasites, duplicated centrosomes remain clustered over the mass of unsegmented nuclei with failed karyokinesis. This failure leads to the formation of an abnormal nuclear mass, while cytokinesis occurs normally. Altogether, our data suggest that PfCAP-H plays a crucial role in maintaining the structural integrity of the condensin I complex on the mitotic chromosomes and is essential for the asexual development of malarial parasites. Importance Mitosis is a fundamental process for Plasmodium parasites, which plays a vital role in their survival within two distinct hosts - human and Anopheles mosquitoes. Despite its great significance, our comprehension of mitosis and its regulation remains limited. In eukaryotes, mitosis is regulated by one of the pivotal complexes known as condensin complexes. The condensin complexes are responsible for chromosome condensation, ensuring the faithful distribution of genetic material to daughter cells. While condensin complexes have recently been identified in Plasmodium spp , our understanding of how this complex is assembled and their precise functions during the blood stage development of Plasmodium falciparum remains largely unexplored. In this study, we investigate the role of a central protein, PfCAP-H, during the blood stage development of P. falciparum . Our findings reveal that PfCAP-H is essential and plays a pivotal role in upholding the structure of condensin I and facilitating karyokinesis.
Research Square · 2024-09-23
preprintOpen access
Recent grants
Molecular mechanisms of schizogony in malaria parasites
NIH · $3.1M · 2019–2025
NIH · $2.6M · 2018
NIH · $397k · 2013
NIH · $1.8M · 2018
Frequent coauthors
- 42 shared
Sabrina Absalon
Indiana University – Purdue University Indianapolis
- 28 shared
Danny W. Wilson
University of Adelaide
- 24 shared
Ana Karla Cepeda Diaz
Boston Children's Hospital
- 24 shared
Karin Blomqvist
Karolinska University Hospital
- 23 shared
Alexander A. Morano
Boston Children's Hospital
- 22 shared
Rachel M. Rudlaff
Harvard University
- 22 shared
James Blauwkamp
- 20 shared
Vasant Muralidharan
University of Georgia
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