After receiving his B.A. in Natural Sciences (Biochemistry) from the University of Cambridge, Dr. Mak pursued his postgraduate research at the Imperial Cancer Research Fund (now Francis Crick Institute) and obtained his Ph.D. from University College London in 2000. He then joined Professor Gary Ruvkun’s laboratory at Harvard Medical School for postdoctoral research on genetic regulation of diapause and lipid metabolism in the nematode C. elegans. From 2006-2013, he was a faculty member at the Stowers Institute for Medical Research and led an independent research group that studied cellular regulation of fat storage and mobilization. During this period, he received the March of Dimes Basil O’Connor Starter Scholar Research Award. In 2013, he joined the Division of Life Science at the HKUST as an Associate Professor.

Research Question

Obesity is the leading cause of type-2 diabetes, cardiovascular diseases and hypertension, the so-called Metabolic Syndrome. We are broadly interested in how body fat level is maintained in animals and how it can be disrupted through genetic and dietary perturbations. At the sub-cellular level, we focused on lipid droplets, which are conserved organelles that are central to the storage and utilization of fat. This is important because the size and number of lipid droplets vary in different cell types and may determine their tolerance to the toxic effect of excess fat.

Research Approach

Our laboratory uses the nematode C. elegans as a discovery tool to elucidate the genetic pathways and molecular mechanisms that regulate food intake, fat storage and mobilization. We seek to address the following questions: (1) what are the regulatory mechanisms that govern lipid droplet size; (2) how do lipid droplets physically and functionally couple with other intracellular organelles; (3) what are the mechanisms for protein targeting and retention to lipid droplets? Most of our studies begin with large-scale forward genetic screens in C. elegans. We then employ genetics, lipid and protein biochemistry, high-throughput sequencing technology, fluorescence and electron microscopy to address our questions at a molecular level in C. elegans and mammalian models.

Representative Publications

1. Cao Z, Fung CW, Mak HY. A Flexible Network of Lipid Droplet Associated Proteins Support Embryonic Integrity of C. elegans. Front Cell Dev Biol. 2022 Apr 4;10:856474.
2. Zeng L, Li X, Preusch CB, He GJ, Xu N, Cheung TH, Qu J, Mak HY. Nuclear receptors NHR-49 and NHR-79 promote peroxisome proliferation to compensate for aldehyde dehydrogenase deficiency in C. elegans. PLoS Genet. 2021 Jul 8;17(7):e1009635.
3. Cao Z, Hao Y, Fung CW, Lee YY, Wang P, Li X, Xie K, Lam WJ, Qiu Y, Tang BZ, Shui G, Liu P, Qu J, Kang BH, Mak HY. Dietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain. Nat Commun. 2019 Jul 1;10(1):2902.
4. Klemm RW, Norton JP, Cole RA, Li CS, Park SH, Crane MM, Li L, Jin D, Boye-Doe A, Liu TY, Shibata Y, Lu H, Rapoport TA, Farese RV Jr, Blackstone C, Guo Y, Mak HY. A conserved role for atlastin GTPases in regulating lipid droplet size. Cell Rep. 2013 May 30;3(5):1465-75.
5. Xu N, Zhang SO, Cole RA, McKinney SA, Guo F, Haas JT, Bobba S, Farese RV Jr, Mak HY. The FATP1-DGAT2 complex facilitates lipid droplet expansion at the ER-lipid droplet interface. J Cell Biol. 2012 Sep 3;198(5):895-911.

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