Hui-Ying Lim, PhD
Associate Professor of Physiology
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, optical and confocal imaging and the power of Drosophila genetics. My lab was the first to identify that reactive oxygen species (ROS) are produced under normal, non-stressed condition in the heart and they direct non-myocyte to myocyte communication that critically regulate proper heart development and function. We are focusing on Kune, a select septate junction protein and a claudin, in mediating the intercellular ROS signaling in the heart. We showed that among over 20 septate junction proteins present in the heart, Kune is a select septate junction protein that directs the paracrine regulatory effect of physiological ROS in the non-myocytes on cardiomyocyte function. We have evidence that Kune elicits such an effect via the regulation of a Drosophila transient receptor potential (dTRP) cation channel protein in the cardiomyocytes. In light of emerging studies that claudins could interact with TRP vanilloid (TRPV) calcium channel proteins in the intestinal and kidney cells to regulate calcium handling, we are pursuing the hypothesis that Kune controls normal heart function by regulating the TRP-mediated calcium influx and homeostasis in the cardiomyocytes. Another research interest in the lab centers on the endocrine function of the heart on systemic lipid homeostasis regulation. Through large-scale genetic screens, we identified several cardiac factors that when their levels are altered in the heart could alter lipid metabolism in other tissues and at the organismal level. First, we showed that high dietary fat can induce the differential increased cardiac production of apolipoprotein B (apoB)-containing lipoproteins (apoB-lipoproteins) over other tissues that in turn promotes obesity in whole flies. Therefore the heart can respond critically to changes in nutrition to evoke metabolic effects not only in the heart but also systemically. Second, we identified that the Snail family transcription factors (Sna TFs) act in the heart to maintain normal systemic lipid homeostasis by controlling the expression of Tep2, a member of the thioester-containing family of secreted proteins that are known to be innate immune effectors but with unclear role in energy metabolism. We show that upon release from the heart, Tep2 travels in the circulation to the fat body (insect adipose tissue) to control TGF-beta signaling and lipid storage in the fat body. We are studying the mechanism by which Tep2 regulates TGF-beta signaling and downstream lipid events in the fat body. Our work reveals a novel role of an immune factor Tep2 in mediating a metabolic link between the heart and adipose tissue. Finally, our lab is investigating intercellular endoplasmic reticulum (ER) stress transmission in the heart and the consequences on heart function. We have evidence that ER stress induced in one cell type can be propagated to neighboring ER stress-naïve cells in vivo in the fly heart. We are currently investigating the molecular mechanisms underlying such a transmission and the effect on heart function and systemic lipid homeostasis.
- B.S. Microbiology, National University of Singapore, Singapore
- Ph.D. Pathobiology, Columbia University, New York
- Postdoctoral. Genetics, Sanford Burnham Prebys Medical Discovery Institute, San Diego
- Stress signaling on heart function and development
- Heart control of systemic obesity
04/01/2020 - 03/31/2025 -National Institutes of Health
National Heart, Lung, and Blood Institute
“A cardiac Wingless-Snail-Tep2 axis directs normal lipid homeostasis and protects against diet-induced obesity”
- Li, Y, Wang, W, Lim, H-Y†. (2023) Drosophila transmembrane protein 214 (dTMEM214) regulates midgut glucose uptake and systemic glucose homeostasis. Developmental Biology. DOI: 10.1016/j.ydbio.2023.01.006. PMID:36657508. †Corresponding author
- Li, Y, Wang, W, Lim, H-Y†. (2021) Drosophila Solute Carrier 5A5 regulates systemic glucose homeostasis by mediating glucose absorption in the Midgut. International Journal of Molecular Sciences. DOI: 10.3390/ijms222212424. PMID: 34830305. †Corresponding author
- Lim, H-Y†, Wang W, Nakagawa Y, Pierzchala-Koziec K. (2020) The Endocine Regulation of Systemic Energy Homeostasis Under Physiological and Pathological Conditions. Front Physiol. PMCID:PMC 33192620. (Editorial) †Corresponding author
- Liu, Y, Bao H, Wang, W†, Lim, H-Y†. (2019) Cardiac Snail family of transcription factors direct systemic lipid metabolism in Drosophila. PLOS Genetics. PMCID:PMC 31725726. †Corresponding author
- Lim, H-Y†., Bao, H., Wang, W. (2019) Select septate junction proteins direct ROS-mediated paracrine regulation of Drosophila cardiac function. Cell Reports. PMCID:PMC6703176. †Corresponding author
- 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. PMCID:PMC5283750. †Corresponding author
- Griffin, TM., Humphries, KM., Kinter, M., Lim, H-Y., Szweda, LI (2015) Nutrient sensing and utilization: Getting to the heart of metabolic flexibility. Biochemie. 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 Reports. PMCID: PMC4164050. †Corresponding author (selected for Cover Image).
- Lim, H-Y and Bodmer, R (2011) Phospholipid homeostasis and lipotoxic cardiomyopathy: A matter of balance. Fly (Austin). 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 and Development. PMCID:PMC3022264.
- Wessells, R., Fitzgerald, E., Piazza, N., Ocorr, K., Morley, S., Davies, C., Lim, H-Y., Elmén, L., Hayes, M., Oldham, S., Bodmer, R (2009) d4EBP acts downstream of both dTOR and dFOXO to modulate cardiac functional aging in Drosophila. Aging Cell. PMCID: PMC2832479.
- Ocorr, K., Perrin, L., Lim, H-Y., Qian, L., Wu, X., Bodmer, R (2007) Genetic Control of heart function and aging in Drosophila. Trends Cardiovascular Medicine. PMCID:PMC1950717.
- Lim, H-Y., Bodmer, R. and Perrin, L (2006) Drosophila Ageing 2005/2006. Experimental Gerontology. 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. PMCID:PMC16914498.