John C. Samuelson, MD, PhD
Professor, Molecular & Cell Biology
Biography
Our lab studies the glycobiology of protozoan parasites that cause diarrhea (Cryptosporidium and Giardia), dysentery (Entamoeba), birth defects (Toxoplasma), and blindness (Acanthamoeba). In particular, we use mass spectrometric, biochemical, and genetic methods to characterize sugars added to glycoproteins, as well as the enzymes that make or remove these sugars (glycosyltransferases and glycosyl hydrolases, respectively). For example, we showed that asparagine-linked glycans (N-glycans) of Cryptosporidium have a single mannose arm that is hardly modified and so is distinct from complex, highly modified N-glycans of the host. In contrast, Cryptosporidium vaccine candidates have mucin-like domains densely modified with O-GalNAc that resemble host intestinal mucins. We discovered a large set of nuclear proteins of Toxoplasma that are decorated with O-linked fucose and showed that O-fucosyltransferase is a homolog of plant Spindly. The host is lacking Spindly but has an O-GlcNAc transferase with a similar structure to Spindly that modifies an even larger set of nucleocytosolic proteins. We also identified a second Toxoplasma O-fucosyltransferase that modifies a secreted protein MIC2, which is essential for parasite adherence to and invasion into host cells.
The Samuelson lab also studies sugar polymers and glycoproteins present in cyst and oocyst walls of these parasites, which are critical for their transmission from person to person. The simple model we have developed is that these walls contain sugar polymers similar to those in fungal and plant walls: chitin (Entamoeba), glucan (Toxoplasma), and cellulose, chitin, and xylan (Acanthamoeba). In contrast to fungi and plants, glycoproteins in the parasite walls are few and are for the most part lectins (proteins that bind sugars), which bind the sugar polymers. These wall lectins are unique to each parasite and may be targets for diagnostic reagents. Finally, we have explored the potential use of alcohol-based hand sanitizers to prevent transmission of Giardia, Entamoeba, and Acanthamoeba.
Other Positions
- Professor, Virology, Immunology & Microbiology, Boston University Chobanian & Avedisian School of Medicine
- Faculty, National Emerging Infectious Disease Lab, Boston University
- Member, Genome Science Institute, Boston University
- Member, Bioinformatics Graduate Program, Boston University
- Graduate Faculty (Primary Mentor of Grad Students), Boston University Chobanian & Avedisian School of Medicine, Graduate Medical Sciences
Education
- Harvard Medical School, MD
- Harvard Medical School, PhD
- Swarthmore College, BA
Publications
- Published on 3/4/2025
Kanakapura Sundararaj B, Goyal M, Samuelson J. Targets for the diagnosis of Acanthamoeba eye infections include four cyst wall proteins and the mannose-binding domain of the trophozoite mannose-binding protein. mSphere. 2025 Mar 25; 10(3):e0094824. PMID: 40035521.
Read at: PubMed - Published on 2/6/2025
Tiwari M, Gas-Pascual E, Goyal M, Popov M, Matsumoto K, Grafe M, Gräf R, Haltiwanger RS, Olszewski N, Orlando R, Samuelson JC, West CM. Novel antibodies detect nucleocytoplasmic O-fucose in protist pathogens, cellular slime molds, and plants. mSphere. 2025 Feb 25; 10(2):e0094524. PMID: 39912628.
Read at: PubMed - Published on 8/13/2024
Kanakapura Sundararaj B, Goyal M, Samuelson J. Cellulose binding and the timing of expression influence protein targeting to the double-layered cyst wall of Acanthamoeba. mSphere. 2024 Sep 25; 9(9):e0046624. PMID: 39136454.
Read at: PubMed - Published on 4/19/2023
van der Wel H, Garcia AM, Gas-Pascual E, Willis MM, Kim HW, Bandini G, Gaye MM, Costello CE, Samuelson J, West CM. Spindly is a nucleocytosolic O-fucosyltransferase in Dictyostelium and related proteins are widespread in protists and bacteria. Glycobiology. 2023 Apr 19; 33(3):225-244. PMID: 36250576.
Read at: PubMed - Published on 10/17/2021
Liu L, Veis J, Reiter W, Motari E, Costello CE, Samuelson JC, Ammerer G, Levin DE. Regulation of Pkc1 Hyper-Phosphorylation by Genotoxic Stress. J Fungi (Basel). 2021 Oct 17; 7(10). PMID: 34682295.
Read at: PubMed - Published on 11/23/2020
Bandini G, Agop-Nersesian C, van der Wel H, Mandalasi M, Kim HW, West CM, Samuelson J. The nucleocytosolic O-fucosyltransferase SPINDLY affects protein expression and virulence in Toxoplasma gondii. J Biol Chem. 2020 Nov 23; 296:100039. PMID: 33410402.
Read at: PubMed - Published on 11/23/2020
Bandini G, Agop-Nersesian C, van der Wel H, Mandalasi M, Kim HW, West CM, Samuelson J. The nucleocytosolic O-fucosyltransferase SPINDLY affects protein expression and virulence in Toxoplasma gondii. J Biol Chem. 2021 Jan-Jun; 296:100039. PMID: 33158988.
Read at: PubMed - Published on 5/16/2019
Magistrado-Coxen P, Aqeel Y, Lopez A, Haserick JR, Urbanowicz BR, Costello CE, Samuelson J. The most abundant cyst wall proteins of Acanthamoeba castellanii are lectins that bind cellulose and localize to distinct structures in developing and mature cyst walls. PLoS Negl Trop Dis. 2019 05; 13(5):e0007352. PMID: 31095564.
Read at: PubMed - Published on 2/18/2019
Bandini G, Albuquerque-Wendt A, Hegermann J, Samuelson J, Routier FH. Protein O- and C-Glycosylation pathways in Toxoplasma gondii and Plasmodium falciparum. Parasitology. 2019 12; 146(14):1755-1766. PMID: 30773146.
Read at: PubMed - Published on 12/11/2018
Bandini G, Leon DR, Hoppe CM, Zhang Y, Agop-Nersesian C, Shears MJ, Mahal LK, Routier FH, Costello CE, Samuelson J. O-Fucosylation of thrombospondin-like repeats is required for processing of microneme protein 2 and for efficient host cell invasion by Toxoplasma gondii tachyzoites. J Biol Chem. 2019 02 08; 294(6):1967-1983. PMID: 30538131.
Read at: PubMed
View 116 more publications: View full profile at BUMC