photo_lim2Hui-Ying Lim, Ph.D.



Appointments:

  • Assistant Professor

 Special Interests:

  • Reactive oxygen species (ROS) signaling on heart function and development
  • Molecular mechanisms of obesity and diabetes regulation

 Training:

  • B.S. Microbiology, National University of Singapore, Singapore
  • Ph.D. Pathobiology, Columbia University, New York
  • Postdoctoral. Sanford Burnham Prebys Medical Discovery Institute, San Diego

 Research Summary:

The overall goal of the research in the Lim lab is to understand the molecular genetic mechanisms that govern cardiac physiology and energy metabolism, by utilizing an integrated approach of cell biology, biochemistry, sophisticated optical imaging and the power of Drosophila genetics. From large-scale genetic screens conducted in the lab, Dr. Lim has identified genes with novel roles in the regulation of energy metabolism. One of the genes identified was dTmem214, a predicted multi-pass transmembrane protein. Further studies in the lab discovered a novel role of dTmem214 in the fly intestinal cells in controlling glucose absorption. Collaborating work performed in Dr. Weidong Wang’s lab at OUHSC identified a similar function of Tmem214 in the mouse enterocytes, thus demonstrating  a conserved and important role of Tmem214 in regulating glucose homeostasis. Studies on the elucidation of the molecular mechanisms underlying the Tmem214 control of glucose absorption in flies and mice are underway. Another research direction in the lab is to study the heart control of systemic lipid metabolism. Using the fly model, the lab has identified the apolipoprotein B (apoB)-containing lipoproteins as a new player that mediate the heart control of systemic lipid homeostasis. Traditionally thought to be mainly produced by the liver and intestine, the lab has found that the apoB-lipoproteins are also generated by the heart and the heart-derived apoB-lipoproteins critically regulate nutrient uptake from the intestine, thereby contributing to the maintenance of whole-body lipid homeostasis. In addition to apoB-lipoproteins, the lab has also recently identified a family of zinc-finger transcription factors that act in the cardiomyocytes to critically regulate lipid storage in other tissues such as the adipose tissue and intestine. Work is now underway to define the upstream regulators and downstream effectors of these transcription factors in the cardiomyocytes that mediate the heart control of systemic lipid metabolism. Last but not least, the lab is actively studying the role of physiological ROS in the non-myocytes on the paracrine control of cardiomyocyte function. We have previously identified a physiological ROS-D-p38 MAPK signaling cascade in the non-myocytes that elicit paracrine regulation of the neighboring cardiomyocyte function. However, the underlying mechanisms remain unknown. Our recent studies have further identified that two select members of the multi-component septate junction (SJ) complex are key effectors of key effectors of ROS-D-p38 signaling in PCs on proper cardiomyocyte function control. Current literature on the SJ is mainly focused on the identification of new protein components that act in concert with existing SJ proteins to mediate the transepithelial barrier. Our work provides first evidence suggesting that the select SJ proteins can serve a dual role as core structural elements of the SJ and key signaling mediators of physiological ROS.

 Relevant Publications:

  • Lee, SJ., Bao, H., Ishikawa, Z., Wang, W., and Lim, H-Y (2017) Cardiomyocyte regulation of systemic lipid metabolism by the apolipoprotein B-containing lipoproteins in Drosophila. PLOS Genetics. DOI:10.1371/journal.pgen.1006555. Corresponding author

  • Duan, H., Li, Y., Arora, D., Xu, D., Lim, H-Y., Wang W* (2017) Discovery of a benzamide derivative as potent pancreatic beta cell agent against endoplasmic reticulum stress. Journal of Medicinal Chemistry. DOI: 10.1021/acs. jmedchem.7b00435.

  • Duan H., Lee JW*., Moon SW., Arora D., Lim, H-Y., Wang W* (2016) Discovery, Synthesis and Evaluation of 2,4-diaminoquinazolines as a Novel Class of Pancreatic β Cell-Protective Agents against ER Stress. Journal of Medicinal Chemistry. DOI:10.1021/acs. jmedchem.6b00041.

  • Griffin, TM., Humphries, KM., Kinter, M., Lim, H-Y., Szweda, LI (2015) Nutrient sensing and utilization: Getting to the heart of metabolic flexibility. Biochemie., S0300-9084(15)00331-4. PMCID: 26476002. (Review) All authors contributed equally to this work.

  • Lim, H-Y., Wang, W., Chen, J., Ocorr, K., Bodmer, R (2014) ROS regulate cardiac function via a distinct paracrine mechanism. Cell Rep., 7:35-44. Corresponding author (selected for Cover Image). PMCID: PMC4164050.

  • Lim, H-Y and Bodmer, R (2011) Phospholipid homeostasis and lipotoxic cardiomyopathy:  A matter of balance. Fly (Austin)., 5:234-236. PMCID: PMC3225766.

  • Lim, H-Y., Wang, W., Wessells, RJ., Ocorr, K., Bodmer, R (2011) Phospholipid homeostasis regulates lipid metabolism and cardiac function through SREBP signaling in Drosophila. Genes Dev., 25:189-200.PMCID:PMC3022264.

  • Lim, H-Y., Bodmer, R. and Perrin, L (2006) Drosophila Ageing 2005/2006. Exp. Geront., 41:1213-1216. PMCID:PMC1855203.

  • Lim, H-Y and Tomlinson, A (2006) Organization of the peripheral fly eye: the roles of Snail family transcription factors in peripheral retinal apoptosis. Development., 33: 3529-3537.(Highlighted in Development 2006 133: 1802. A Snail trail to Wg-induced death).

Current Funding: 

  • 07/01/2015 - 06/30/2020        National Institutes of Health

       National Heart, Lung, and Blood Institute

       1R01HL128455-01

       “ROS signaling, intercellular communication and heart development and function”

        Role: PI