John C Samuelson, MD, PhD
Professor
Boston University Henry M. Goldman School of Dental Medicine
Dept of Molecular & Cell Biology

MD, Harvard Medical School
PhD, Harvard Medical School



Entamoeba histolytica, Giardia lamblia, and Trichomonas are simple eukaryotes, which cause dysentery, diarrhea, and vaginitis, respectively. Our laboratory uses molecular biological methods to study the biochemistry, cell biology, pathogenesis, and evolution of these important human pathogens.

One project attempts to determine the composition of the walls of Entamoeba cysts, which are the infectious and diagnostic form. Chitin in cyst wall is made by stage-specific chitin synthases and is modified by endogenous chitin deacetylases and chitinases. Chitin fibrils in the wall are held together unique lectins , which have multiple chitin-binding domains. Post-translation modifications of the cyst wall lectins include addition of unusual O-phosphodiester-linked sugars and cleavages between chitin-binding domains. Identification of these cyst wall-associated lectins may lead to better diagnostic reagents for distinguishing pathogenic from non-pathogenic amebae.

A second project, which is performed in collaboration with my colleague Phillips Robbins, attempts to understand Asn-linked glycosylation in Entamoeba, Giardia, and other protists . In particular, we use bioinformatics to predict lipid-linked N-glycan precursors, as well as N-glycan associated proteins involved in quality control in the ER lumen. We test our predictions using biochemical methods, which include determinations of carbohydrate structures and purification of glycoproteins by lectin columns. These studies suggest 1) the present diversity of N-glycans derives in part from secondary loss of genes encoding enzyme involved in N-glycan precursor synthesis, 2) protists with short N-glycans lack N-glycan-dependent quality control, and 3) there is Darwinian selection for sites of N-glycans in secreted proteins of diverse eukaryotes and viruses. Unique parasite sugars may be novel vaccine candidates or targets for anti-microbial lectins.

A third project is concerned with how Entamoeba, Giardia, and Trichomonas adapt to the anaerobic environment in the intestinal lumen. We have identified an atrophic mitochondrion-derived organelle, which lacks enzymes of oxidative phosphorylation in Entamoeba. We have also identified numerous bacterium-like fermentation enzymes in these protists, which appear to have been obtained by lateral gene transfer (LGT). Although LGT is frequent between bacteria, it is unusual between bacteria and eukaryotes. Two of the bacterial genes acquired by LGT appear to be important for activating and inactivating metronidazole, the best drug against these organisms.


Professor
Boston University School of Medicine
Microbiology


Graduate Faculty (Primary Mentor of Grad Students)
Boston University School of Medicine, Division of Graduate Medical Sciences


Member
Boston University
Bioinformatics Graduate Program



2006-2011 Member of the Pathogenic Eukaryotes study section (2006-2011)
1998-2000 U.S.-India Fund Award (1998-2000)
1994-1996 1994-96 Harvard Digestive Diseases Center Pilot Project (1994-1996)
1993-1995 U.S. Mexico Foundation for Science Award (1993-1995)
1989-1992 American Gastroenterology Association Industry Scholar (1989-1992)
1986-1989 Life Science Research Foundation Fellow (1986-1989)
1984 Harvard Medical School: Shipley Award for best published research
1979-1984 National Institute of Health: Medical Scientist Training Program Fellow (1979-1984)


Genetic modification of cultured Cryptosporidium to test the autoinfection model
02/01/2017 - 01/31/2018 (PI)
NIH/National Institute of Allergy & Infe
1R21AI130889-01

Structure and development of oocyst and sporocyst walls
08/01/2015 - 01/31/2018 (PI)
NIH/National Institute of Allergy & Infe
5R01AI110638-03

Glycobiology of Giardia
05/01/2011 - 04/30/2017 (PI)
NIH/National Institute of Allergy & Infe
5R01AI048082-10

Roles for Beta 1,3-glucan in oocyst walls of Toxoplasma and Eimeria
04/01/2013 - 03/31/2014 (PI)
Mizutani Foundation for Glycosciences

Multiple Lectin Model of the Cyst Wall of Entamoeba
03/01/2000 - 02/28/2013 (PI)
NIH/National Institute of Allergy & Infe
5R01AI044070-10




Yr Title Project-Sub Proj Pubs
2017 Genetic modification of cultured Cryptosporidium to test the autoinfection model 1R21AI130889-01
2017 Structure and Development of Oocyst and Sporocyst Walls 5R01AI110638-03 1
2016 Structure and Development of Oocyst and Sporocyst Walls 5R01AI110638-02 1
2015 Structure and Development of Oocyst and Sporocyst Walls 1R01AI110638-01A1 1
2015 Glycobiology of Giardia 5R01AI048082-10 20
2014 Glycobiology of Giardia 5R01AI048082-09 20
2013 Glycobiology of Giardia 5R01AI048082-08 20
2012 Glycobiology of Giardia 5R01AI048082-07 20
2012 Glycobiology of Giardia 3R01AI048082-07S1 20
2011 CYST WALL ENDOPROTEASES AND GLYCANS OF PARASITES 5P41RR010888-15-5121 236
Showing 10 of 42 results. Show All Results
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

  1. Haserick JR, Klein JA, Costello CE, Samuelson J. Cryptosporidium parvum vaccine candidates are incompletely modified with O-linked-N-acetylgalactosamine or contain N-terminal N-myristate and S-palmitate. PLoS One. 2017; 12(8):e0182395.View Related Profiles. PMID: 28792526.
  2. Aqeel Y, Rodriguez R, Chatterjee A, Ingalls RR, Samuelson J. Killing of diverse eye pathogens (Acanthamoeba spp., Fusarium solani, and Chlamydia trachomatis) with alcohols. PLoS Negl Trop Dis. 2017 Feb; 11(2):e0005382.View Related Profiles. PMID: 28182670; DOI: 10.1371/journal.pntd.0005382;.
  3. Haserick JR, Leon DR, Samuelson J, Costello CE. Asparagine-Linked Glycans of Cryptosporidium parvum Contain a Single Long Arm, Are Barely Processed in the Endoplasmic Reticulum (ER) or Golgi, and Show a Strong Bias for Sites with Threonine. Mol Cell Proteomics. 2017 Apr; 16(4 suppl 1):S42-S53.View Related Profiles. PMID: 28179475; DOI: 10.1074/mcp.M116.066035;.
  4. Sanz S, López-Gutiérrez B, Bandini G, Damerow S, Absalon S, Dinglasan RR, Samuelson J, Izquierdo L. The disruption of GDP-fucose de novo biosynthesis suggests the presence of a novel fucose-containing glycoconjugate in Plasmodium asexual blood stages. Sci Rep. 2016 Nov 16; 6:37230.View Related Profiles. PMID: 27849032; DOI: 10.1038/srep37230;.
  5. Bandini G, Haserick JR, Motari E, Ouologuem DT, Lourido S, Roos DS, Costello CE, Robbins PW, Samuelson J. O-fucosylated glycoproteins form assemblies in close proximity to the nuclear pore complexes of Toxoplasma gondii. Proc Natl Acad Sci U S A. 2016 Oct 11; 113(41):11567-11572.View Related Profiles. PMID: 27663739.
  6. Chatterjee A, Bandini G, Motari E, Samuelson J. Ethanol and isopropanol in concentrations present in hand sanitizers sharply reduce excystation of Giardia and Entamoeba and eliminate oral infectivity of Giardia cysts in gerbils. Antimicrob Agents Chemother. 2015 Nov; 59(11):6749-54.View Related Profiles. PMID: 26282413; PMCID: PMC4604385; DOI: 10.1128/AAC.01290-15;.
  7. Chatterjee A, Ratner DM, Ryan CM, Johnson PJ, O'Keefe BR, Secor WE, Anderson DJ, Robbins PW, Samuelson J. Anti-Retroviral Lectins Have Modest Effects on Adherence of Trichomonas vaginalis to Epithelial Cells In Vitro and on Recovery of Tritrichomonas foetus in a Mouse Vaginal Model. PLoS One. 2015; 10(8):e0135340.View Related Profiles. PMID: 26252012; PMCID: PMC4529277; DOI: 10.1371/journal.pone.0135340;.
  8. Samuelson J, Robbins PW. Effects of N-glycan precursor length diversity on quality control of protein folding and on protein glycosylation. Semin Cell Dev Biol. 2015 May; 41:121-8.View Related Profiles. PMID: 25475176; PMCID: PMC4452448; DOI: 10.1016/j.semcdb.2014.11.008;.
  9. Samuelson J, Bushkin GG, Chatterjee A, Robbins PW. Strategies to discover the structural components of cyst and oocyst walls. Eukaryot Cell. 2013 Dec; 12(12):1578-87.View Related Profiles. PMID: 24096907; PMCID: PMC3889564; DOI: 10.1128/EC.00213-13;.
  10. Bushkin GG, Motari E, Carpentieri A, Dubey JP, Costello CE, Robbins PW, Samuelson J. Evidence for a structural role for acid-fast lipids in oocyst walls of Cryptosporidium, Toxoplasma, and Eimeria. MBio. 2013; 4(5):e00387-13.View Related Profiles. PMID: 24003177; PMCID: PMC3760245; DOI: 10.1128/mBio.00387-13;.
Showing 10 of 113 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 112 publications over 34 distinct years, with a maximum of 8 publications in 1997

YearPublications
19802
19811
19823
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19891
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19936
19946
19952
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19978
19982
19993
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20032
20055
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20076
20087
20094
20107
20111
20121
20132
20141
20152
20162
20173
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75 E. Newton St Evans Building
Boston MA 02118
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