Functional Genetics and Metabolism Laboratory

Dr. Kim’s research program focuses on genetic and metabolic regulation of heart development, function and disease, with emphasis on obesity, diabetes and heart failure.

First, we are interested in the molecular function and mechanism of Iroquois (Irx) transcription factors in the heart, which are not only implicated in organ development, but also in energy homeostasis regulation. We are currently investigating the individual and overlapping functions of Irx proteins in the development and disease of the cardiac conduction system and ventricular chambers.

Second, we are investigating the metabolism of the heart and its communications with other core metabolic tissues/organs (e.g., adipose tissue and liver).

Using genetically engineered mice as our primary models, we integrate physiology with molecular and systems biology approaches to address the fundamental questions of heart function and diseases.

The laboratory is supported by the Canadian Institutes of Health Research (CIHR), the Heart and Stroke Foundation of Canada (HSFC), the Canada Foundation for Innovation (CFI), the Natural Sciences and Engineering Research Council of Canada (NSERC), the J. P. Bickell Foundation for Medical Research, and uOttawa Translational Research Grant.

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Publications

See current publications list at PubMed.

Selected publications:

  • Asif S, Kim RY, Fatica T, Sim J, Zhao X, Oh Y, Denoncourt A, Cheung AC, Downey M, Mulvihill EE, Kim KH. (2022) Hmgcs2-mediated ketogenesis modulates high fat diet-induced hepatosteatosis. Molecular Metabolism 101494. doi: 10.1016/j.molmet.2022.101494
  • Kim KH§, Oh Y, Liu J, Dababneh S, Kim RY, Ban KW, Husain M, Hui CC, Backx PH§. (2022) Irx5 regulates cardiac contractility via KV4.2-encoded transient outward K+ currents. American Journal of Physiology – Heart and Circulatory Physiology doi: 10.1152/ajpheart.00572.2021 (§, co-corresponding authors)
  • Son JE, Dou Z, W Siyi, Chan J, Mo R, Li, X, Huang X, Kim KH, Michaud JL, Hui CC. (2021) Ectopic expression of Irx3 and Irx5 in the paraventricular nucleus of the hypothalamus contributes to defects in Sim1 haploinsufficiency. Science Advances 7(44):eabh4503
  • Son JE, Dou Z, Kim KH, W Siyi, Cha VSB, Mo R, Zhang X, Ketela T, Li X, Huang X, Hui CC. (2021) Irx3 and Irx5 in Ins2-Cre+ cells regulate hypothalamic postnatal neurogenesis and leptin response. Nature Metabolism 3(5):701-713
  • Asif S, Morrow NM, Mulvihill EE, Kim KH. (2020) Understanding Dietary Intervention-mediated Epigenetic Modifications in Metabolic Diseases. Frontiers in Genetics 11:590369
  • Kim RY, Lee JH, Oh Y, Sung HK, Kim KH. (2019) Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice. J Vis Exp. 2019 Nov 27;(153). doi: 10.3791/60174.
  • Kim YH, Lee JH, Yeung JL, Das E, Kim RY, Jiang Y, Moon JH, Jeong H, Thakkar N, Son JE, Trzaskalski N, Hui CC, Doh KO, Mulvihill EE, Kim JR, Kim KH#, Sung HK#. (2019) Thermogenesis-independent metabolic benefits conferred by isocaloric intermittent fasting in ob/ob mice. Scientific Reports. 21;9(1):2479 (#, co-corresponding authors)
  • Kim KH, Kim YH, Moon JH, Son JE, Kim S, Choe MS, Zhong J, Lee JH, Fu K, Lenglin F, Park JG, Bilan PJ, Klip A, Nagy A, JR Kim, Hussein SM, Doh KO, Hui CC, Sung HK. (2017) Intermittent fasting Promotes Metabolic Improvement and Adipose Thermogenesis via VEGF-mediated Alternative Activation of Adipose Macrophage. Cell Research. 27(11):1309-1326
  • Kim KH, Rosen A, Hussain SM, Puviindran V, Korogyi AS, Chiarello C, Nagy A, Hui CC, Backx PH. (2016) Irx3 is required for Postnatal Development of the Mouse Ventricular Conduction System. Scientific Reports. 6, 19197; doi: 10.1038/srep19197.
  • Smemo S*, Tena JJ*, Kim KH*, Gamazon ER, Sakabe NJ, Gómez-Marín C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nobrega MA (2014) Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature. 507(7492):371-5. (*, co-first authors)
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Staff

Current team members:

  • Yena Oh, MSc, PhD candidate
  • Termeh Aslani, MSc candidate
  • Serena Pulente, MSc candidate (co-supervision with Dr. Erin Mulvihill)
  • Hyejin Lee, Undergraduate research student
  • Rimshah Abid, Honours thesis student
  • Julie Pan, Honours thesis student
  • Reshani Jeyaratnam, Undergraduate research student
  • Ye En Kim, Undergraduate research student
  • Saif Dababneh, BSc, Research project student (MD-PhD student at UBC)
  • Gagan Geekee, BSc, Medical student
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Projects

  • The function and molecular mechanism of Irx3 in the ventricular conduction system programming in the developing and diseased heart.
  • Transcriptional and non-transcriptional functions of Irx5 in the diseased heart.
  • The overlapping function of Irx3/4 during the ventricular compaction process of the heart.
  • Developmental role of Irx1 in the electrophysiological properties of the atrioventricular conduction system.
  • Metabolic flexibility and responses of the heart to maintain its functions during nutritional and metabolic challenges.
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Available Positions

To enquire about available positions, please submit your CV with a cover letter detailing what you can bring to the team.

Contact:
@email

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