FEND for TB

The Feasibility of Novel Diagnostics for TB in Endemic Countries (FEND for TB) program supports the evaluation of early-stage diagnostics and novel diagnostic strategies for TB, in TB endemic countries to address an urgent need for improved tuberculosis (TB) diagnostics.

Cell-Analysis Technique Could Combat Tuberculosis

NIH Awards Grants to Support Bacteriophage Therapy Research

Study Could Explain Tuberculosis Bacteria Paradox

TB Portals

The NIAID TB Portals Program is a multi-national collaboration for tuberculosis (TB) data sharing and analysis to advance TB research.

TB Portals is a web-based, open-access repository of multi-domain TB data and tools for its analysis. It offers linked socioeconomic/geographic, clinical, laboratory, radiological, and genomic data from over 3,400 international TB patient cases.

Researchers can explore and analyze these data through any of the tools. TB Portals data are also available for download to support your own research.

Landmark TB Trial Identifies Shorter-Course Treatment Regimen

Elodie Ghedin, Ph.D.

Chief, Systems Genomics Section
  • Respiratory virus transmission and evolution
  • Microbial interactions in respiratory infections (influenza, COVID-19, tuberculosis)
  • Host-parasite interactions in filarial worm infections

Biography

Dr. Elodie Ghedin obtained her Ph.D. from McGill University’s Institute of Parasitology in Montreal, Canada. Following a postdoctoral fellowship at NIAID on the cell biology of Leishmania donovani, in 2000 she joined The Institute for Genomic Research (TIGR; now the J. Craig Venter Institute) where she worked on the annotation of trypanosomatid genomes. There she led her own group on the Brugia malayi and Influenza Virus genome projects. In 2006 she joined the University of Pittsburgh School of Medicine where she was part of the Department of Computational and Systems Biology and the Center for Vaccine Research. In 2014 she moved to New York University where she was a professor of biology in the College of Arts and Sciences, and a professor of epidemiology in the School of Global Public Health. From 2017 to 2019, she served as director of NYU’s Center for Genomics and Systems Biology. In May 2020, Dr. Ghedin joined NIAID’s Laboratory of Parasitic Diseases as a senior investigator. She also holds an affiliated position with New York University. Dr. Ghedin is a MacArthur Foundation Fellow (2011), a Kavli Frontier of Science Fellow (2012), and an American Academy of Microbiology Fellow (2017).

Program Description

Our systems biology research program meets at the interface of microbiology, molecular virology, systems biology, and genomics and focuses on the molecular basis of microparasite (virus and bacteria) diversity and interaction in transmission and virulence and macroparasite (nematodes) adaptation to niches in their human hosts. The overarching question is, How do pathogens adapt to their hosts, and what is the evolutionary basis of this adaptation?

Predictive modeling of clinical outcomes in respiratory infections

We develop and use new analytical tools to define genetic structure and mechanisms of evolutionary change in respiratory viruses sampled within individual hosts over the course of an infection and across chains of transmission. We have observed that the dynamics of evolution of respiratory viruses like influenza are different in pre-immune versus naïve hosts and in high-risk populations, such as immunocompromised and obese individuals. In light of the COVID-19 pandemic, we have expanded our research program to include SARS-CoV-2 to pursue questions on transmission, factors associated with disease severity, and host selection pressure on the evolution of the virus. Our goal is to integrate systems-wide data and map molecular interaction networks to build predictive models of COVID-19 severity. (Collaborations with Dr. Lara Mahal, University of Alberta; Dr. Stacey Schultz-Cherry, St. Jude Children’s Research Hospital; Dr. David Gresham, Center for Genomics and Systems Biology, New York University; Dr. Ted Ross, University of Georgia; Dr. Mirella Salvatore, Weil Cornell Medicine)

Related Projects

  • Determining intra-host diversity and phylogeny of SARS-CoV-2 (collaborations with Dr. Mark Mulligan, New York University Grossman School of Medicine; Dr. Sanchita Das, NIH Clinical Center; Dr. Marta Luksza, Icahn School of Medicine at Mt. Sinai; Dr. Michael Lassig, University of Cologne; Dr. Robert Paulino Ramirez, Universidad Iberoamericana, Dominican Republic; Dr. Jacques Boncy, Ministry of Health, Haiti)
  • Profiling the respiratory microbiome and antibiotic resistance (collaborations with Dr. Leopold Segal, New York University Langone; Dr. Richard Bonneau, New York University and the Flatiron Institute; Dr. Aubree Gordon, University of Michigan; Dr. Anna Roca, LSHTM/MRC, The Gambia)
  • Functional analyses of the respiratory microbiome in tuberculosis (collaboration with Dr. Philana Lin and Dr. JoAnne Flynn, University of Pittsburgh School of Medicine)

Filarial nematodes infect millions of individuals and represent the leading cause of morbidity in the developing world. Current medications are inadequate for control and elimination, necessitating a better understanding of the basic biology of these worms. Most filarial nematodes, including Brugia malayi and Onchocerca volvulus (causative agents of lymphatic filariasis and river blindness, respectively) have an essential intracellular bacterial endosymbiont, Wolbachia. Our studies address key questions on the reciprocal cues required in the co-dependency between the worm and the bacteria.

Related Projects

  • Modeling the interplay between filarial worms and their endosymbiont (collaborations with Dr. Stefania Giacomello, ScieLifeLab, Sweden; Dr. John Parkinson, University of Toronto; Dr. Sara Lustigman, New York Blood Center)
  • Identifying promoter motifs involved in nematode development (collaborations with Dr. Lonnie Welch, Ohio University; Dr. Thomas Unnasch, University of South Florida)
  • Discovering new metabolites and immunomodulators (collaborations with Dr. Drew Jones, New York University Grossman School of Medicine; Dr. Dirk Trauner, New York University)

Research Group

Denis Voronin, Ph.D.
Staff Scientist
M.S., Biology, Novosibirsk State University, Russia
PhD, Institute of Cytology and Genetics, Novosibirsk, Russia

Denis trained as a postdoctorate fellow at Université Claude Bernard Lyon 1 and at the Liverpool School of Tropical Medicine before joining the New York Blood Center where he became Assistant Member of the Cellular Microbiology Research Program. Denis is focused on delineating the essential cellular processes that define symbiotic Wolbachia-host interactions in filarial nematodes. Elimination of the symbiont leads to death of the adult worm, rendering Wolbachia an attractive target for interventional tools to combat filariasis.

Martha Nelson, Ph.D.
Visiting Staff Scientist
B.A. Biology, Amherst College, MA
Ph.D. Biology, The Pennsylvania State University, PA

Martha was a Research Fellow and Staff Scientist at the Division of International Epidemiology and Populations Studies (DIEPS) of the Fogarty International Center. She is currently a visiting fellow in SGS to pursue her work in influenza and SARS-CoV-2 genomic epidemiology.

Yin-Ting (Tim) Yeh, Ph.D.
Visiting Scientist (Research Assistant Prof, PSU)
B.S., Engineering and System Science, and Material Science Engineering, National Tsing-Hua University, Taiwan
M.S., Chemical and Biochemical Engineering, University of Notre-Dame, IN
Ph.D., Biomedical Engineering, The Pennsylvania State University, PA

Tim is a visiting scientist in SGS. His research focuses on a combination of enhanced Raman spectroscopy, the development and application of a virus enrichment microfluidic device, and suitable deep learning algorithms to rapidly detect viruses, their antigenic variants and track genetic and antigenic evolution in real-time. This work is part of collaborations with Dr. Mauricio Terrones at PSU, and Dr. Steve Jacobson at NINDS/NIH.

Allison Roder, Ph.D.
Computational Biologist
B.S., Biotechnology and Molecular Bioscience, and Computer Science, Rochester Institute of Technology
PhD, Molecular Genetics and Microbiology, Duke University

Allison is studying the evolution of SARS-CoV-2 in populations at risk, and the host response to Influenza A and B viruses.

Matthew Chung, Ph.D.
Computational Biologist
B.S., Microbiology, G. H. Cook Scholar, Rutgers University, NJ
PhD, Molecular Microbiology and Immunology, Institute for Genome Sciences, University of Maryland Baltimore

Matt specializes in the computational analysis of genomics, metagenomics, and transcriptomics data sets in the analysis of the respiratory microbiome in COVID19 and COPD patients.

Stephanie Banakis, M.S.
Lab Manager and Biologist
B.S., Bioengineering, University of Illinois at Chicago
M.S., Biology, New York University

Stephanie studies the evolution of the Influenza virus and of SARS-CoV-2 in populations at risk.

Wei Wang, M.S.
Biologist
Bachelor of Medicine, Tongji Medical University, Wuhan, China
M.S., Microbiology, North Dakota State University, ND

Wei has over 20 years of experience in cell culture with expertise in molecular virology and vaccine research.

Joseph Koussa, Ph.D.
Post-doctoral IRTA
B.Sc., Biology, University of Ottawa, Canada
M.S., Molecular Biology, Lebanese American University, Lebanon

Joe held a faculty position at New York University Abu Dhabi where he served as an Instructor in the Division of Natural Sciences for four years.

Joe’s project revolves around host-parasite interactions in lymphatic filariasis with an emphasis on sex-dependent interactions between adult male and female parasitic worms and the host’s lymphatic endothelial cells. He has a keen interest in glycobiology of host-parasite interactions and adopts a glycocentric approach to the identification of biologically active effector parasite molecules.

Alexandra Mushegian, Ph.D.
Post-doctoral IRTA
A.B., Organismic and Evolutionary Biology, Harvard University
Ph.D., Universitat Basel, Zoology

Sasha is broadly interested in the ecology and evolution of pathogens, parasites and vectors. In the SGS lab, she is working on SARS-CoV-2. One set of questions revolves around within-host viral diversity of clinical samples and whether it can help us inform epidemiological surveillance or clinical practice. A second project is on characterizing the genomic epidemiology of SARS-CoV-2 in the Caribbean.

Abdoulie Bojang, Ph.D.
Post-doctoral Visiting IRTA (APTI)
B.Sc., Bioscience and Health, Leeds Metropolitan University, UK
M.Sc., Biomedical science, University of Hull, UK
Ph.D., Open University, UK
Higher scientific officer, Medical Research Council unit, The Gambia
Postdoctoral researcher, Medical Research Council unit, The Gambia

Abdoulie joined SGS in August 2021. His project in the SGS is to assess by metagenomics the impact of intrapartum oral azithromycin on the nasopharyngeal microbiome of Gambian infants.  Oral azithromycin given during labor appears to be a promising intervention to ultimately decrease neonatal mortality and to reduce incidence of clinical infection among mother (mastitis, fever) and their babies (skin infection).  However, the impact of the intervention on the nasopharyngeal microbiome of infants is not yet known.  

Michael Frimpong, Ph.D.
Post-doctoral Visiting IRTA (APTI)
B.Sc., Medical Laboratory Technology, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
Ph.D., Immunity and Infectious Diseases, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

Michael joined SGS in August 2021. His research is focused on using metagenomics to understand the pathogenesis of skin neglected tropical diseases, particularly Buruli ulcer and how that information can be used to improve treatment outcomes.

Brent Edwards, B.A.
Post-bac IRTA
B.A., Biology, Middlebury College, VT

Brent is mentored by Dr. Denis Voronin and his project is focused on the intracellular bacteria Wolbachia and the mechanisms by which the bacteria interacts with its mosquito and filarial nematode hosts. Specifically, he is studying the effects of Wolbachia in mosquito cells infected with Zika virus and the molecular basis for why Wolbachia presence is associated with Zika virus suppression. A second project investigates the endosymbiotic relationship between Wolbachia and filarial nematodes to identify potential drug targets for the treatment and prevention of lymphatic filariasis.

Anil Chakravorty, B.S.
Post-bac IRTA
B.S., Integrative Biology Honors program, minor in Chemistry, University of Illinois at Urbana-Champaign, IL

Anil works with Dr. Allison Roder and investigates the gene expression profiles of host cells in response to infection with Influenza A and B. Currently, most transcriptomic analyses focus on influenza A infection, in part due to its pandemic potential; there is a paucity of information regarding host response to influenza B infection.

Christopher Mederos, B.S.
Post-bac IRTA
B.S., Biochemistry, Florida International University in Miami, FL.

Chris is working on two projects. The first, under the mentorship of Dr. Allison Roder, is to investigate the evolutionary transmission dynamics of SARS-CoV-2 and intra-host single nucleotide variants (iSNVs). The second project, under the mentorship of Dr. Joe Koussa, investigates the role of secreted lipid-binding proteins in the infection of Brugia malayi in humans.

Daniela Chow, B.S.
Post-bac IRTA (INRO)
B.S., Biological Sciences, The University of Texas at El Paso, TX

Daniela, under the mentorship of Dr. Joe Koussa, is studying the interplay of Brugia malayi with human lymphatic endothelial cells and its contribution in pathogenesis. She is also determining the role of Brugia malayi Galectin-2 (lec-2) in host-parasite interactions.

Allie Kreitman, B.A.
Post-bac IRTA (INRO)
B.A., Molecular Biology, minor in Math, Colorado College, CO

Allie’s project, under the mentorship of Dr. Sasha Mushegian, is to characterize the genomic epidemiology of SARS-CoV-2 in the Dominican Republic and Haiti. She is also comparing samples collected from symptomatic and asymptomatic individuals infected with SARS-CoV-2.

RyeAnne Ricker, B.S.
Ph.D. candidate, Biomedical Engineering, George Washington University
B.S., Biological Engineering, Montana State University, MT
B.S., Microbiology – Medical Laboratory Science, Montana State University, MT

RyeAnne worked as a microbiologist for 2 years at the Public health Labs for the State of Washington, Division of Disease Control & Health Statistics, before starting her graduate program at GWU. In her graduate research in SGS, she uses Machine Learning techniques to characterize viruses by their Raman spectrum. The aim of this work is to generate rapid methods for detection and identification of viruses as well as to better understand how a Raman fingerprint can be used to infer relationships between viruses.

RyeAnne is a National Science Foundation Fellow (2021-2024), and she has received the 2021 Terry Collins Distinguished Doctoral Award.

Selected Publications

Visit PubMed for a complete publication list.

Section or Unit Name
Systems Genomics Section
First Name
Elodie
Last Name
Ghedin
Suffix
Ph.D.
Exclude from directory
Off
Section/Unit: Year Established
Section/Unit: Location
This Researcher/Clinician’s Person Page
Program Description

Our systems biology research program meets at the interface of microbiology, molecular virology, systems biology, and genomics and focuses on the molecular basis of microparasite (virus and bacteria) diversity and interaction in transmission and virulence and macroparasite (nematodes) adaptation to niches in their human hosts. The overarching question is, How do pathogens adapt to their hosts, and what is the evolutionary basis of this adaptation?

Predictive modeling of clinical outcomes in respiratory infections

We develop and use new analytical tools to define genetic structure and mechanisms of evolutionary change in respiratory viruses sampled within individual hosts over the course of an infection and across chains of transmission. We have observed that the dynamics of evolution of respiratory viruses like influenza are different in pre-immune versus naïve hosts and in high-risk populations, such as immunocompromised and obese individuals. In light of the COVID-19 pandemic, we have expanded our research program to include SARS-CoV-2 to pursue questions on transmission, factors associated with disease severity, and host selection pressure on the evolution of the virus. Our goal is to integrate systems-wide data and map molecular interaction networks to build predictive models of COVID-19 severity. (Collaborations with Dr. Lara Mahal, University of Alberta; Dr. Stacey Schultz-Cherry, St. Jude Children’s Research Hospital; Dr. David Gresham, Center for Genomics and Systems Biology, New York University; Dr. Ted Ross, University of Georgia; Dr. Mirella Salvatore, Weil Cornell Medicine)

Related Projects

  •   Determining intra-host diversity and phylogeny of SARS-CoV-2 (collaborations with Dr. Sanchita Das, NIH Clinical Center; Dr. James Musser, Houston Methodist; Dr. Robert Paulino Ramirez, Universidad Iberoamericana, Dominican Republic; Dr. Jacques Boncy, Ministry of Health, Haiti)
  •  Profiling the respiratory microbiome and antibiotic resistance (collaborations with Dr. Leopold Segal, New York University Langone; Dr. Richard Bonneau, New York University and the Flatiron Institute; Dr. Aubree Gordon, University of Michigan; Dr. Anna Roca, LSHTM/MRC, The Gambia)
  • Development of virus enrichment and detection platforms for rapid identification of novel viruses by Raman spectroscopy and machine learning (collaboration with Dr. Mauricio Terrones, Dr. Sharon Huang, Dr. Shengxi Huang)

Host-parasite interactions in filarial worm infections

Filarial nematodes infect millions of individuals and represent the leading cause of morbidity in the developing world. Current medications are inadequate for control and elimination, necessitating a better understanding of the basic biology of these worms. Most filarial nematodes, including Brugia malayi and Onchocerca volvulus (causative agents of lymphatic filariasis and river blindness, respectively) have an essential intracellular bacterial endosymbiont, Wolbachia. Our studies address key questions on the reciprocal cues required in the co-dependency between the worm and the bacteria.

Related Projects

  • Modeling the interplay between filarial worms and their endosymbiont (collaborations with Dr. Stefania Giacomello, ScieLifeLab, Sweden; Dr. John Parkinson, University of Toronto; Dr. Sara Lustigman, New York Blood Center)
  • Identifying promoter motifs involved in nematode development (collaborations with Dr. Lonnie Welch, Ohio University; Dr. Thomas Unnasch, University of South Florida)
  • Discovering new metabolites and immunomodulators (collaborations with Dr. Drew Jones, New York University Grossman School of Medicine; Dr. Dirk Trauner, New York University)
Selected Publications

DeGrace MM, Ghedin E, Frieman MB, Krammer F, Grifoni A, Alisoltani A, Alter G, Amara RR, Baric RS, Barouch DH, Bloom JD, Bloyet LM, Bonenfant G, Boon ACM, Boritz EA, Bratt DL, Bricker TL, Brown L, Buchser WJ, Carreño JM, Cohen-Lavi L, Darling TL, Davis-Gardner ME, Dearlove BL, Di H, Dittmann M, Doria-Rose NA, Douek DC, Drosten C, Edara VV, Ellebedy A, Fabrizio TP, Ferrari G, Fischer WM, Florence WC, Fouchier RAM, Franks J, García-Sastre A, Godzik A, Gonzalez-Reiche AS, Gordon A, Haagmans BL, Halfmann PJ, Ho DD, Holbrook MR, Huang Y, James SL, Jaroszewski L, Jeevan T, Johnson RM, Jones TC, Joshi A, Kawaoka Y, Kercher L, Koopmans MPG, Korber B, Koren E, Koup RA, LeGresley EB, Lemieux JE, Liebeskind MJ, Liu Z, Livingston B, Logue JP, Luo Y, McDermott AB, McElrath MJ, Meliopoulos VA, Menachery VD, Montefiori DC, Mühlemann B, Munster VJ, Munt JE, Nair MS, Netzl A, Niewiadomska AM, O'Dell S, Pekosz A, Perlman S, Pontelli MC, Rockx B, Rolland M, Rothlauf PW, Sacharen S, Scheuermann RH, Schmidt SD, Schotsaert M, Schultz-Cherry S, Seder RA, Sedova M, Sette A, Shabman RS, Shen X, Shi PY, Shukla M, Simon V, Stumpf S, Sullivan NJ, Thackray LB, Theiler J, Thomas PG, Trifkovic S, Türeli S, Turner SA, Vakaki MA, van Bakel H, VanBlargan LA, Vincent LR, Wallace ZS, Wang L, Wang M, Wang P, Wang W, Weaver SC, Webby RJ, Weiss CD, Wentworth DE, Weston SM, Whelan SPJ, Whitener BM, Wilks SH, Xie X, Ying B, Yoon H, Zhou B, Hertz T, Smith DJ, Diamond MS, Post DJ, Suthar MS. Defining the risk of SARS-CoV-2 variants on immune protection. Nature. 2022 May;605(7911):640-652.  

Nussenblatt V, Roder AE, Das S, de Wit E, Youn JH, Banakis S, Mushegian A, Mederos C, Wang W, Chung M, Pérez-Pérez L, Palmore T, Brudno JN, Kochenderfer JN, Ghedin E. (2022) Yearlong COVID-19 Infection Reveals Within-Host Evolution of SARS-CoV-2 in a Patient With B-Cell Depletion. J Infect Dis. 2022 Apr 1;225(7):1118-1123. 

Sulaiman I, Chung M, Angel L, Tsay JJ, Wu BG, Yeung ST, Krolikowski K, Li Y, Duerr R, Schluger R, Thannickal SA, Koide A, Rafeq S, Barnett C, Postelnicu R, Wang C, Banakis S, Pérez-Pérez L, Shen G, Jour G, Meyn P, Carpenito J, Liu X, Ji K, Collazo D, Labarbiera A, Amoroso N, Brosnahan S, Mukherjee V, Kaufman D, Bakker J, Lubinsky A, Pradhan D, Sterman DH, Weiden M, Heguy A, Evans L, Uyeki TM, Clemente JC, de Wit E, Schmidt AM, Shopsin B, Desvignes L, Wang C, Li H, Zhang B, Forst CV, Koide S, Stapleford KA, Khanna KM, Ghedin E, Segal LN. (2021) Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome. Nat Microbiol. 2021 Aug 31. 

Foster JM, Grote A, Mattick J, Tracey A, Tsai YC, Chung M, Cotton JA, Clark TA, Geber A, Holroyd N, Korlach J, Li Y, Libro S, Lustigman S, Michalski ML, Paulini M, Rogers MB, Teigen L, Twaddle A, Welch L, Berriman M, Dunning Hotopp JC, Ghedin E. Sex chromosome evolution in parasitic nematodes of humans. Nat Comm. 2020 Apr 23;11(1):1964. 

Zhang L, Forst CV, Gordon A, Gussin G, Geber AB, Fernandez PJ, Ding T, Lashua L, Wang M, Balmaseda A, Bonneau R, Zhang B, Ghedin E. Characterization of antibiotic resistance and host-microbiome interactions in the human upper respiratory tract during influenza infection. Microbiome. 2020 Mar 17;8(1):39.

Yeh YT, Gulino K, Zhang Y, Sabestien A, Chou TW, Zhou B, Lin Z, Albert I, Lu H, Swaminathan V, Ghedin E, Terrones M. A rapid and label-free platform for virus capture and identification from clinical samples. Proc Natl Acad Sci U S A.  2020 Jan 14;117(2):895-901.

Visit PubMed for a complete publication list.

Additional Information

Research Network

Center for Influenza Vaccine Research for High-Risk Populations (CIVR-HRP) https://www.niaidcivics.org/center-for-influenza-vaccine-research-for-high-risk-populations-civr-hrp/

NSF Growing Convergence Program
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1934977

Training Program

NIH Oxford-Cambridge Scholars Program https://oxcam.gpp.nih.gov/about

 

Major Areas of Research
  • Respiratory virus transmission and evolution
  • Microbial interactions in respiratory infections (influenza, COVID-19, tuberculosis)
  • Host-parasite interactions in filarial worm infections
Research Group Page

Joshua Tan, Ph.D.

Chief, Antibody Biology Unit
Earl Stadtman Tenure-Track Investigator

Major Areas of Research

  • Biology of antibody response to Plasmodium falciparum
  • Characterization of human monoclonal antibodies to infectious pathogens

Program Description

Human monoclonal antibodies are emerging as powerful tools in combating infectious disease, both as direct prophylactics and as reagents to identify vulnerable sites on pathogens to guide vaccine design. At the Antibody Biology Unit (ABU), we aim to use cutting-edge technology to study B cells at the single cell level and to identify and characterize human monoclonal antibodies against a range of pathogens. We have two major aims:

  1. To study basic antibody biology. The sequences of monoclonal antibodies isolated from a vaccinated or naturally infected individual provide a high-resolution portrait of the antibody response to a given pathogen. Information revealed includes the predominant antibody isotype that is generated, the degree of somatic mutation and affinity maturation required for the development of a potent neutralizing response, and the preferential usage of specific VH genes to mount a response against a given antigen.
  2. To investigate the use of monoclonal antibodies for prevention of infection and as tools for vaccine design. Monoclonal antibodies that are isolated will be screened in in vitro and in vivo assays to determine their potency in preventing infection. Their affinity for their targets will be measured using biophysical assays. In collaboration with structural biologists, we will identify the specific epitopes targeted by the most potent antibodies and develop these sites as novel vaccine candidates. The most potent antibodies will also be considered as candidates to prevent infection in early-phase clinical trials.

The primary focus of the unit will be on malaria. Plasmodium falciparum causes approximately 400,000 deaths a year and remains a serious global health threat. Antibodies have been shown to be key mediators of protection against different stages of the P. falciparum life cycle, but the antibody response to malaria has only recently been studied at high resolution. The biology of the antibody response to P. falciparum is complex and fascinating. Recently, we identified broadly reactive antibodies from individuals living in malaria-endemic areas that contain a LAIR1 insert (an extra immunoglobulin-like domain) that is originally encoded in a different chromosome. This insert confers broad reactivity and is somatically mutated along with the rest of the antibody. This insertion event appears to be quite common in individuals living in different malaria-endemic regions (5-10% of individuals). In a separate study, we identified potent human monoclonal antibodies targeting a novel epitope on the P. falciparum circumsporozoite protein, the major sporozoite coat protein. This site is now being investigated as a new vaccine candidate.

Our platform is adaptable to any target. This unit will also study human monoclonal antibodies against other infectious agents, including Mycobacterium tuberculosis and SARS-CoV-2, as well as non-infectious targets.

Biography

Joshua Tan, Ph.D., is a Stadtman Tenure-track Investigator and an NIH Distinguished Scholar in the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases. He received his Ph.D. from the University of Oxford, England. Prior to joining the NIH, he was awarded the Pfizer Research Prize for his malaria work and the Sir Henry Wellcome Postdoctoral Fellowship to investigate human monoclonal antibodies that target the malaria-causing parasite P. falciparum.

Research Group

Andrew Cooper, Ph.D., Postdoctoral Fellow
Cherrelle Dacon, Ph.D., Postdoctoral Fellow
Divya Mohan, Biologist
Lauren Purser, Lab Manager
Lawrence Wang, Visiting PhD Student
Courtney Tucker, Ph.D. Student

Selected Publications

Cho H, Gonzales-Wartz KK, Huang D, Yuan M, Peterson M, Liang J, Beutler N, Torres JL, Cong Y, Postnikova E, Bangaru S, Talana CA, Shi W, Yang ES, Zhang Y, Leung K, Wang L, Peng L, Skinner J, Li S, Wu NC, Liu H, Dacon C, Moyer T, Cohen M, Zhao M, Lee FE, Weinberg RS, Douagi I, Gross R, Schmaljohn C, Pegu A, Mascola JR, Holbrook M, Nemazee D, Rogers TF, Ward AB, Wilson IA, Crompton PD and Tan J. 2021 Bispecific antibodies targeting distinct regions of the spike protein potently neutralize SARS-CoV-2 variants of concern. Sci Transl Med 13, eabj5413.

Tan J, Cho H, Pholcharee T, Pereira LS, Doumbo S, Doumtabe D, Flynn BJ, Schön A, Kanatani S, Aylor SO, Oyen D, Vistein R, Wang L, Dillon M, Skinner J, Peterson M, Li S, Idris AH, Molina-Cruz A, Zhao M, Olano LR, Lee PJ, Roth A, Sinnis P, Barillas-Mury C, Kayentao K, Ongoiba A, Francica JR, Traore B, Wilson IA, Seder RA and Crompton PD. 2021. Functional human IgA targets a conserved site on malaria sporozoites. Sci Transl Med 13, abg2344.

Tan J, Piccoli L and Lanzavecchia A. 2019. The antibody response to Plasmodium falciparum: cues for vaccine design and the discovery of receptor-based antibodies. Annu Rev Immunol 37, 225-246.

Tan J, Sack BK, Oyen D, Zenklusen I, Piccoli L, Barbieri S, Foglierini M, Fregni CS, Marcandalli J, Jongo S, Abdulla S, Perez L, Corradin G, Varani L, Sallusto F, Sim BKL, Hoffman SL, Kappe SHI, Daubenberger C, Wilson IA and Lanzavecchia A. 2018. A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein. Nat Med 24, 401-407.

Pieper K, Tan J, Piccoli L, Foglierini M, Barbieri S, Chen Y, Fregni CS, Wolf T, Jarrossay D, Anderle M, Abdi A, Ndungu FM, Doumbo OK, Traore B, Tran TM, Jongo S, Zenklusen I, Crompton PD, Daubenberger C, Bull PC, Sallusto F and Lanzavecchia A. 2017. Public antibodies to malaria antigens generated by two LAIR1 insertion modalities. Nature 548, 597-601.

Tan J, Pieper K, Piccoli L, Abdi A, Foglierini M, Geiger R, Tully CM, Jarrossay D, Ndungu FM, Wambua J, Bejon P, Fregni CS, Fernandez-Rodriguez B, Barbieri S, Bianchi S, Marsh K, Thathy V, Corti D, Sallusto F, Bull P and Lanzavecchia A. 2016. A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens. Nature 529, 105-109.

Visit PubMed for a complete publication listing.

Section or Unit Name
Antibody Biology Unit

Highlight

Lab/Program Name
First Name
Joshua
Last Name
Tan
Suffix
Ph.D.
Exclude from directory
Off
Section/Unit: Location
This Researcher/Clinician’s Person Page
Parent Lab/Program
Program Description

Human monoclonal antibodies are emerging as powerful tools to combat infectious disease. At the Antibody Biology Unit (ABU), we aim to use cutting-edge technology to study B cells at the single-cell level and to identify and characterize human monoclonal antibodies against a range of pathogens. The Unit currently focuses on diseases with substantial burden globally or in the United States.

ABU has two main objectives:

  1. Investigate the use of monoclonal antibodies for the prevention of infection and as tools for immunogen design: An array of tools, including the Berkeley Lights Beacon and Carterra LSA, will be used for high-throughput antibody identification and characterization. Monoclonal antibodies that are isolated will be screened in in vitro and in vivo assays to determine their potency in preventing infection. Their affinity for their targets will be measured using biophysical assays. In collaboration with structural biologists, we will identify the specific epitopes targeted by the most potent antibodies and develop these sites as novel immunogens. The most potent antibodies will also be considered as candidates to prevent infection in early-phase clinical trials.
  2. Study basic antibody biology: The sequences of monoclonal antibodies isolated from an immunized or naturally infected individual provide a high-resolution portrait of the antibody response to a given pathogen. Information revealed includes the predominant antibody isotype that is generated, the degree of somatic mutation and affinity maturation required for the development of a potent neutralizing response, and the preferential usage of specific VH genes to mount a response against a given antigen. 
Selected Publications

Dacon C, Moskovitz R, Swearingen K, Da Silva Pereira L, Flores-Garcia Y, Aleshnick M, Kanatani S, Flynn B, Molina-Cruz A, Wollenberg K, Traver M, Kirtley P, Purser L, Dillon M, Bonilla B, Franco A, Petros S, Kritzberg J, Tucker C, Paez GG, Gupta P, Shears MJ, Pazzi J, Edgar JM, Teng AA, Belmonte A, Oda K, Doumbo S, Krymskaya L, Skinner J, Li S, Ghosal S, Kayentao K, Ongoiba A, Vaughan A, Campo JJ, Traore B, Barillas-Mury C, Wijayalath W, Idris A, Crompton PD, Sinnis P, Wilder BK, Zavala F, Seder RA, Wilson IA, Tan J. Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein. Science. 2025 Jan 3;387(6729):eadr0510.

Wang LT, Cooper AJR, Farrell B, Miura K, Diouf A, Müller-Sienerth N, Crosnier C, Purser L, Kirtley PJ, Maciuszek M, Barrett JR, McHugh K, Ogwang R, Tucker C, Li S, Doumbo S, Doumtabe D, Pyo CW, Skinner J, Nielsen CM, Silk SE, Kayentao K, Ongoiba A, Zhao M, Nguyen DC, Lee FE, Minassian AM, Geraghty DE, Traore B, Seder RA, Wilder BK, Crompton PD, Wright GJ, Long CA, Draper SJ, Higgins MK, Tan J. Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5. Cell. 2024 Sep 5;187(18):4981-4995.e14. 

Dacon C, Peng L, Lin TH, Tucker C, Lee CD, Cong Y, Wang L, Purser L, Cooper AJR, Williams JK, Pyo CW, Yuan M, Kosik I, Hu Z, Zhao M, Mohan D, Peterson M, Skinner J, Dixit S, Kollins E, Huzella L, Perry D, Byrum R, Lembirik S, Murphy M, Zhang Y, Yang ES, Chen M, Leung K, Weinberg RS, Pegu A, Geraghty DE, Davidson E, Doranz BJ, Douagi I, Moir S, Yewdell JW, Schmaljohn C, Crompton PD, Mascola JR, Holbrook MR, Nemazee D, Wilson IA, Tan J. Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses. Cell Host Microbe. 2023 Jun 14;31(6):1071-1072.

Dacon C, Tucker C, Peng L, Lee CD, Lin TH, Yuan M, Cong Y, Wang L, Purser L, Williams JK, Pyo CW, Kosik I, Hu Z, Zhao M, Mohan D, Cooper AJR, Peterson M, Skinner J, Dixit S, Kollins E, Huzella L, Perry D, Byrum R, Lembirik S, Drawbaugh D, Eaton B, Zhang Y, Yang ES, Chen M, Leung K, Weinberg RS, Pegu A, Geraghty DE, Davidson E, Douagi I, Moir S, Yewdell JW, Schmaljohn C, Crompton PD, Holbrook MR, Nemazee D, Mascola JR, Wilson IA, Tan J. Broadly neutralizing antibodies target the coronavirus fusion peptide. Science. 2022 Jul 12:eabq3773.

Cho H, Gonzales-Wartz KK, Huang D, Yuan M, Peterson M, Liang J, Beutler N, Torres JL, Cong Y, Postnikova E, Bangaru S, Talana CA, Shi W, Yang ES, Zhang Y, Leung K, Wang L, Peng L, Skinner J, Li S, Wu NC, Liu H, Dacon C, Moyer T, Cohen M, Zhao M, Lee FE, Weinberg RS, Douagi I, Gross R, Schmaljohn C, Pegu A, Mascola JR, Holbrook M, Nemazee D, Rogers TF, Ward AB, Wilson IA, Crompton PD, Tan J. Bispecific antibodies targeting distinct regions of the spike protein potently neutralize SARS-CoV-2 variants of concern. Sci Transl Med. 2021 Oct 20;13(616):eabj5413.

Tan J, Pieper K, Piccoli L, Abdi A, Perez MF, Geiger R, Tully CM, Jarrossay D, Maina Ndungu F, Wambua J, Bejon P, Fregni CS, Fernandez-Rodriguez B, Barbieri S, Bianchi S, Marsh K, Thathy V, Corti D, Sallusto F, Bull P, Lanzavecchia A. A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens. Nature. 2016 Jan 7;529(7584):105-109.

Visit PubMed for a complete publication listing.

Major Areas of Research
  • Development of monoclonal antibody therapeutics against pathogens
  • Characterization of human antibody response to infectious pathogens
  • Biology of antibody response to influenza, other viruses, Plasmodium falciparum, and Mycobacterium tuberculosis
Research Group Page

TRITON Study

We are studying a condition called paradoxical reaction that some people get when they take treatment for tuberculosis (TB). Most people with TB feel better after starting treatment. But for some people, the opposite happens. They may feel better at first, but then suddenly get worse. This opposite effect is a paradoxical reaction. We do not understand how this reaction happens. It can be hard to tell whether worsening symptoms are caused by a paradoxical reaction or something else, such as if the treatment just is not working.

Contact Information

Volunteer or get more information
Toll free: 1-800-411-1222
TTY: 1-866-411-1010
Se habla español

Emailprpl@mail.cc.nih.gov

Bioinformatics Resource Centers (BRCs) for Infectious Diseases

The NIAID-funded Bioinformatics Resource Centers provide data-driven, production-level, sustainable computational platforms to enable sharing and access to data, portable computational tools, and standards that support interoperability for the infectious diseases research community.