Alvin Kuk

I'm an assistant professor in the City University of Hong Kong (DG) where I currently serve as the associate program coordinator of the biomedical engineering program. Previously I was a postdoc with David Silver at Duke-NUS Medical School. I did my PhD at Duke University where I was advised by Seok-Yong Lee. I've received a Human Frontier Science Program fellowship and a Singapore Young Individual Research Grant.

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Research

We are interested in sugar and lipid metabolism, protein and metabolic engineering, extracellular matrix, and applications to nanomedicine. An enduring theme of our research is the synthesis, remodeling, and recycling of the glycocalyx, a layer of carbohydrates surrounding the cell, with focus on the transporter proteins and membrane protein enzymes that mediate these processes.

The current research focuses on remodeling and salvage of the extracellular matrix (ECM). The ECM is a highly dynamic and information-rich regulator that directly impacts drug delivery, cancer/fibrosis treatment, and regenerative medicine. The research objectives are (1) mechanisms of extracellular ECM remodeling, (2) metabolism and salvage of ingested ECM material, and (3) using the insights gained to develop biomedical engineering solutions for precision nanomedicine.

Our approach integrates fundamental science research utilizing multi-omics (e.g. metabolomics, lipidomics, RNA-seq), cell metabolism (e.g. stable isotope tracing), chemical biology (e.g. click chemistry), protein biochemistry, structural biology/bioinformatics with the engineering design process to meet real-world biomedical problems.

Presented unpublished research advances at the 24th HFSP Awardees Meeting (9-11 July 2025, Melbourne). Two journal manuscripts are currently in writing.

Co-inventors on a UK patent about lysophospholipid production (GB2504160.9).

We were invited to preview two papers that identified FLVCR1 and FLVCR2 to be the transporters mediating choline uptake for de novo phospholipid synthesis.

We introduced an in vitro biochemical assay for lipid flipping by the lysophospholipid transporter Mfsd2a.

We identified the orphan lysosomal protein Spns1 to be the transporter of LPC and LPE lysophospholipids and a key regulator of phospholipid salvage. Ingested phospholipids are digested inside lysosomes and are then salvaged by Spns1 back into cellular phospholipid pools.

We were invited to review the literature on the lipid flippase MurJ which supplies bacteria with building blocks to build cell walls. MurJ is an emerging antibiotic target.

Together with clinical collaborators, we identified human patients carrying genetic mutations in the lysophospholipid transporter Mfsd2a and showed they result in reduced Mfsd2a expression or activity.

We captured additional crystal structures of the lipid flippase MurJ in the inward-closed, inward-open, inward-occluded, and outward-facing conformations, elucidating the mechanism by which it flips lipid-linked building blocks across the cell membrane for bacteria to make their cell walls.

We captured crystal structures of the human membrane protein enzyme DPAGT1 in complex with the natural product tunicamycin, showing how tunicamycin can inhibit N-linked glycosylation. Tunicamycin has potent antibacterial activity but its usefulness as an antibiotic is limited by its off-target inhibition of human DPAGT1. By comparing the structures of DPAGT1-tunicamycin and bacterial MraY-tunicamycin, we were able to design a bacteria-specific tunicamycin analog.

We captured the first crystal structure of the lipid flippase MurJ showing how it can bind and transport lipid-linked peptidoglycan precursors by an alternating access mechanism. Transport of these building blocks across the cell membrane by MurJ is a critical step for bacteria to build cell walls, thereby making MurJ an key target for antibiotics development.

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