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PhD University College London
Associate Professor

Email: hym@ust.hk

Labortatory homepage: http://maklab.ust.hk/lab/


Research Interests

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. Our laboratory uses the nematode C. elegans and mammalian cells to elucidate the genetic pathways and molecular mechanisms that regulate food intake, fat storage and mobilization. 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 microscopy and nanoscopy to address our questions at a molecular level.

Fat storage and mobilization
The lipid droplet is the subcellular organelle where neutral lipids are stored. In metazoans, lipid droplets vary in number and size in different tissues, and they undergo dynamic changes that reflect the metabolic status and dietary intake of the organism as a whole. In the last few years, studies in our laboratory have defined lipid droplets as sub-cellular organelles for fat storage that are conserved from C. elegans to human. We also discovered genetic and dietary regulators of lipid droplet size, as well as a protein complex that facilitates lipid droplet expansion at the ER-lipid droplet interface. Future studies will address the following questions. (1) What are the regulatory mechanisms that govern lipid droplet size as the cellular demand and supply of fat shifts? (2) How do lipid droplets physically and/or functionally couple with other intracellular organelles to store or mobilize fat? (3) What are the mechanisms for protein targeting and retention to lipid droplets?

Transgene silencing and RNAi
In studying the regulation of a triglyceride lipase, we have fortuitously generated a transgene that undergoes periodic silencing. Using this highly sensitive reporter, we have discovered a number of novel genes required for transgene silencing and RNA interference (RNAi). We currently are using an interdisciplinary approach to determine the molecular function of these new RNAi pathway components.


Selected Publications

  1. Li X, Lam WJ, Cao Z, Hao Y, Sun Q, He S, Mak HY, Qu JY. Integrated femtosecond stimulated Raman scattering and two-photon fluorescence imaging of subcellular lipid and vesicular structures. J Biomed Opt. 2015 Nov 1;20(11):110501.

  2. Na H, Zhang P, Chen Y, Zhu X, Liu Y, Liu Y, Xie K, Xu N, Yang F, Yu Y, Cichello S, Mak HY, Wang MC, Zhang H, Liu P. Identification of lipid droplet structure-like/resident proteins in Caenorhabditis elegans. Biochim Biophys Acta. 2015 Oct;1853(10 Pt A):2481-91.

  3. Yang H, Vallandingham J, Shiu P, Li H, Hunter CP, Mak HY. The DEAD box helicase RDE-12 promotes amplification of RNAi in cytoplasmic foci in C. elegans. Curr Biol. 2014 Apr 14;24(8):832-8.

  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.

  6. Yang H, Zhang Y, Vallandingham J, Li H, Florens L, Mak HY. The RDE-10/RDE-11 complex triggers RNAi-induced mRNA degradation by association with target mRNA in C. elegans. Genes Dev. 2012 Apr 15;26(8):846-56.

  7. Hao Y, Xu N, Box AC, Schaefer L, Kannan K, Zhang Y, Florens L, Seidel C, Washburn MP, Wiegraebe W, Mak HY. Nuclear cGMP-dependent kinase regulates gene expression via activity-dependent recruitment of a conserved histone deacetylase complex. PLoS Genet. 2011 May;7(5):e1002065.

  8. Zhang SO, Trimble R, Guo F, Mak HY. Lipid droplets as ubiquitous fat storage organelles in C. elegans. BMC Cell Biol. 2010 Dec 8;11:96.

  9. Zhang SO, Box AC, Xu N, Le Men J, Yu J, Guo F, Trimble R, Mak HY. Genetic and dietary regulation of lipid droplet expansion in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4640-5.

  10. Butcher RA, Ragains JR, Li W, Ruvkun G, Clardy J, Mak HY. Biosynthesis of the Caenorhabditis elegans dauer pheromone. Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1875-9.


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