Institute of Biological Chemistry, Academia Sinica

Research

Our research program is focused in the areas of synthetic chemistry (with a particular emphasis in carbohydrate chemistry), the conformational analysis of oligosaccharides and the design of novel therapeutic agents that act by inhibiting carbohydrate-processing enzymes. Students and postdoctoral fellows in the group use synthetic chemistry to prepare compounds with interesting biological activities and then have the opportunity to use them in either biochemical or conformational studies.

The primary research focus is directed ultimately towards the identification of new drugs for the treatment of tuberculosis. Our approach is to develop inhibitors of the enzymes that assemble the polysaccharide portions of the protective cell wall of the organism responsible for this disease, Mycobacterium tuberculosis. These polysaccharides are unique in that they are comprised largely of monosaccharides in the furanose ring form. The synthesis of these compounds has been largely neglected by synthetic chemists and our efforts involve both total synthesis and the development of new synthetic methods.

We have completed the total synthesis of a 22-residue oligosaccharide that is an important motif found in the mycobacterial cell wall and fragments of this oligosaccharide, and related analogues, are currently being synthesized and explored in the development of novel vaccines for the prevention of tuberculosis. We are also working towards the characterization of glycosyltransferases involved in mycobacterial cell wall biosynthesis.

Degrees and Positions Held

• 1993   Ph.D. , Chemistry, University of Alberta
• 1988   B.A. , Chemistry, University of Montana

• 2019 – present   Director, Institute of Biological Chemistry, Academia Sinica
• 2019 – present   Distinguished Research Fellow, Institute of Biological Chemistry, Academia Sinica
• 2018 – 2021   Chair, Division of Organic Chemistry, University of Alberta, Department of Chemistry
• 2015 – 2021   R. U. Lemieux Chair in Carbohydrate Chemistry
• 2006 – 2021   Professor, University of Alberta
• 2014 – 2020   Scientific Director, Canadian Glycomics Network (NCE)
• 2014 – 2019   Canada Research Chair in Carbohydrate Chemistry (Tier 1)
• 2013 – 2014   Associate Chair, Graduate Studies, University of Alberta, Department of Chemistry
• 2012 – 2015   Scientific Director, Alberta Glycomics Centre
• 2009 – 2011   Associate Director, Science, Alberta Glycomics Centre
• 2009 – 2011   Associate Chair, Graduate Studies, University of Alberta, Department of Chemistry
• 2006 – 2011   Chair, Division of Organic Chemistry, University of Alberta, Department of Chemistry
• 2003 – 2006   Associate Professor, University of Alberta
• 2002 – 2003   Associate Professor, The Ohio State University
• 1996 – 2002   Assistant Professor, The Ohio State University

Selected Publications

Cryo-EM and cryo-ET reveal the molecular architecture and host interactions of mycobacteriophage Douge. 
Maharana J, Wang CH, Tsai LA, Liao YT, Yang CH, Shen MC, Macale LS, Tran TN, Narsico J, Perez RJ, Tewary SK, Wu JL, Lin HY, Chang SW, Franklin A, Moynihan PJ, Jacobs-Sera D, Freeman KG, Hatfull GF, Lowary TL, Ho MC 
Cell Rep., 44(8):116057 (2025)   DOI: 10.1016/j.celrep.2025.116057

Structural insights into terminal arabinosylation of mycobacterial cell wall arabinan. 
Liu Y, Brown CM, Erramilli S, Su YC, Guu SY, Tseng PS, Wang YJ, Duong NH, Tokarz P, Kloss B, Han CR, Chen HY, Rodrigues J, Khoo KH, Archer M, Kossiakoff AA, Lowary TL, Stansfeld PJ, Nygaard R, Mancia F 
Nat Commun., 16(1):3973 (2025)   DOI: 10.1038/s41467-025-58196-5

Exploring a De Novo Route to Bradyrhizose: Synthesis and Isomeric Equilibrium of Bradyrhizose Diastereomers. 
Cunha VLS, O'Doherty GA, Lowary TL 
Chemistry, 30(33):e202400886 (2024)   DOI: 10.1002/chem.202400886

Three-component systems represent a common pathway for extracytoplasmic addition of pentofuranose sugars into bacterial glycans. 
Kelly SD, Duong NH, Nothof JT, Lowary TL, Whitfield C 
Proc Natl Acad Sci U S A., 121(21):e2402554121 (2024)   DOI: 10.1073/pnas.2402554121

Features and protective efficacy of human monoclonal antibodies targeting Mycobacterium tuberculosis arabinomannan. 
Liu Y, Chen T, Zhu Y, Furey A, Lowary TL, Chan J, Bournazos S, Ravetch JV, Achkar JM 
JCI Insight., 8(20):e167960 (2023)   DOI: 10.1172/jci.insight.167960

One-pot regioselective diacylation of pyranoside 1,2-cis diols. 
Kim T, Bell MR, Thota VN, Lowary TL 
J Org Chem., 87(7):4894-4907 (2022)    DOI: 10.1021/acs.joc.2c00252

The retaining β-Kdo glycosyltransferase WbbB uses a double-displacement mechanism with an intermediate adduct rearrangement step. 
Forrester TJB, Ovchinnikova OG, Li Z, Kitova EN, Nothof JT, Koizumi A, Klassen JS, Lowary TL, Whitfield C, Kimber MS 
Nature Communications, 13(1):6277 (2022)   DOI: 10.1038/s41467-022-33988-1

The biosynthetic origin of ribofuranose in bacterial polysaccharides. 
Kelly SD, Williams DM, Nothof JT, Kim T, Lowary TL, Kimber MS, Whitfield C 
Nature Chemical Biology, 18(5):530-537 (2022)   DOI: 10.1038/s41589-022-01006-6

Synthesis of a Tridecasaccharide Lipooligosaccharide Antigen from the Opportunistic Pathogen Mycobacterium kansasii. 
Shen K, Bai B, Liu YH, Lowary TL 
Angewandte Chemie-International Edition, 60(47):24859-24863 (2021)   DOI: 10.1002/anie.202111549

Synthesis of structurally-defined polymeric glycosylated phosphoprenols as potential lipopolysaccharide biosynthetic probes. 
Wang L, Lowary TL 
Chemical Science, 12(36):12192-12200 (2021)   DOI: 10.1039/d1sc03852d

Publication List