Associate Professor

Hoon-Ki Sung

Department of Laboratory Medicine & Pathobiology

MD, PhD

Location
Hospital for Sick Children (SickKids)
Address
686 Bay St., Peter Gilgan Centre for Research and Learning, Room 10.9710, Toronto, Ontario Canada M5G 1X8
Research Interests
Metabolism & Nutrition, Cardiovascular
Appointment Status
Primary

Dr Sung received his M.D. from South Korea in 1997.

In 2004, he obtained his Ph.D. in the Department of Clinical Oriented Anatomy and Functional Histology, University of Yeungnam.

Following his Ph.D., he did his postdoctoral research at the Korea Advanced Institute of Science and Technology (KAIST) in the laboratory of Dr Gou Young Koh.

In 2006, he moved to Toronto and joined the laboratory of Dr Andras Nagy in the Tanenbaum-Lunenfeld Research Institute at Mount Sinai Hospital.

In 2014, he established his laboratory in the Physiology and Experimental Medicine Program at the Hospital for Sick Children Research Institute.

His main research interest includes adipose biology and metabolism, angiogenesis and stem cell.

Research Synopsis

Sung lab is a new research group studying adipose biology and metabolism at The Hospital for Sick Children.

Our research focus includes:

  1. physiological and metabolic role of adipose tissue vascular endothelial growth factor (VEGF)
  2. identification of adipocyte precursor cells and its metabolic function by employing mouse model, gene expression analysis and metabolic analysis.

Obesity is defined as an excess of whole body fat mass (adipose tissue).

Adipose tissue is characterized by its ability for lifelong growth and almost unlimited expansion.

As in other tissues, fat tissue expansion also requires concomitant new vessel formation (angiogenesis) to meet its increased demand for oxygen and nutrients.

Vascular endothelial growth factor A (VEGF) is an endothelial specific potent angiogenic factor and is highly expressed in growing tissues including adipose tissue.

We previously demonstrated that adipose-VEGF exerts metabolic improvement by reducing adipose tissue hypoxia and inflammation through enhanced angiogenesis. In addition, adipose-VEGF induces ‘brown-like’ adipocyte formation (browning) in white adipose tissue, which provides additional metabolic benefits.

However, underlying mechanism for VEGF induced browning and their cellular origin is still unclear. Therefore, in the future study, we will investigate the molecular mechanism of VEGF-mediated beige cells formation and identify the cellular origin of VEGF-induced beige adipocyte.

Recently, we found adipose-VEGF may have a potential to regulate trans-endothelial lipid transportation in white adipose tissue, which might be one of key processes for whole body lipid partitioning and metabolic homeostasis.

These data suggest that adipose-VEGF may contribute to whole body metabolism through its angiogenic as well as non-angiogenic (lipid transportation) function.

Our study will point to the therapeutic potential of adipose-VEGF for the treatment and prevention of obesity and metabolic disease.

Selected Publications

Thomson BR, Heinen S, Jeansson M, Ghosh AK, Fatima A, Sung HK, Onay T, Chen H, Yamaguchi S, Economides AN, Flenniken A, Gale N, Hong YK, Fawzi A, Liu X, Kume T, Quaggin SE. A lymphatic defect causes ocular hypertension and glaucoma in mice. Journal of Clinical Investigation 2014 1;124(10):4320-4

Li H, Qu D, McDonald A, Isaac SM, Whiteley KJ, Sung HK, Nagy A, Adamson SL Trophoblast- Specific Reduction of VEGFA Alters Placental Gene Expression and Maternal Cardiovascular Function in Mice. Biol Reprod. 2014 Aug 13. pii: biolreprod.114.118299

Martinez-Fernandez A, Nelson TJ, Reyes S, Alekseev AE, Secreto F, Perez-Terzic C, Beraldi R, Sung HK, Nagy A, Terzic A. iPS Cell-Derived Cardiogenicity is Hindered by Sustained Integration of Reprogramming Transgenes. Circ Cardiovasc Genet. 2014 Jul 30. pii: CIRCGENETICS.113.000298

Michael IP, Westenskow PD, Hacibekiroglu S, Greenwald AC, Ballios BG, Kurihara T, Li Z, Warren CM, Zhang P, Aguilar E, Donaldson L, Marchetti V, Baba T, Hussein SM, Sung HK, Iruela-Arispe ML, Rini JM, van der Kooy D, Friedlander M, Nagy A. Local acting Sticky-trap inhibits vascular endothelial growth factor dependent pathological angiogenesis in the eye. EMBO Mol Med. 2014 May 1;6(5):604-23. doi: 10.1002/emmm.201303708

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, Nóbrega MA. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature. 2014 Mar 20;507(7492):371-5

Kim M, Park HJ, Seol JW, Jang JY, Cho Y-S, Kim KR, Choi Y, Lydon JP, DeMayo FJ, Shibuya M, Ferrara N, Sung HK, Nagy A, Alitalo K, Koh GY. VEGF-A regulated by progesterone governs uterine angiogenesis and vascular remodeling during pregnancy. EMBO Mol Med 2013.5(9):1415-30

Sung HK, Doh KO, Son JE, Bae Y, Park JG, Bae Y, Choi S, Nelson SM, Nagy K, Michael IP, Koh GY, Adamson SL, Pawson T and Nagy A. Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis. Cell Metabolism 2013. 17(1):61-72.

Han H, Irimia MP. Ross J, Sung HK, Alipanahi B, David L, Golipour A, Gabut M, Michael IP, Nachman EN, Wang E, Trcka D, Thompson T, O’Hanlon D, Slobodeniuc V, Barbosa-Morais NL, Burge CB, Moffat J, Frey FJ, Nagy A, Ellis J, Wrana JL, Blencowe BL. MBNL proteins repress embryonic stem cell-specific alternative splicing and reprogramming. Nature 2013 13;498(7453):241-245.

Michael IP, Monetti C, Chiu A, Zhang P, Baba T, Nishino K, Agha-Mohammadi S, Woltjen K, Sung HK, Nagy A. Highly efficient site-specific transgenesis in cancer cell lines. Mol Cancer 2012. 11-89

Jin J, Sison K, Li C, Tian R, Wnuk M, Sung HK, Jeansson M, Jones N, Kerjaschki D, Shibuya M, Fantus G, Nagy A, Gerber H-P, Ferrara N, Pawson T, Quaggin SE. Soluble FLT1 Binds Lipid Microdomains in Podocytes to Control Cell Morphology and Glomerular Barrier Function. Cell 2012. 12;151(2):384-99

Gabut M, Samavarchi-Tehrani P, Wang X, Slobodeniuc V, O’Hanlon D, Sung HK, Alvarez M, Talukder S, Pan Q, Woltjen K, Mazzono E, Nedelec S, Wichterle H, Hughes TR, Zandstra P, Nagy A, Wrana JL, and Blencowe BJ. An alternative splicing switch regulates transcriptional networks required for embryonic stem cell pluripotency and somatic cell reprogramming. Cell 2011. 147(1):132-46

Mohseni P, Sung HK, Murphy AJ, Laliberte CL, Pallari H-M, Henkelman M, Georgiou J, Xie G, Quaggin SE, Thorner PS, Eriksson JE, Nagy A. Nestin is not essential for development of the central nervous system but required for dispersion of acetylcholine receptor clusters at the area of neuromuscular junctions. J Neurosci. 2011. 31(32):11547-52 

Nagy K, Sung HK, Zhang P, Laflamme S, Vincent P, Agha-Mohammadi S, Woltjen K, Monetti C, Michael IP, Smith LC, Nagy A. Induced pluripotent stem cell lines derived from equine fibroblasts. Stem Cell Rev. 2011. 7(3):693-702

Koh YJ, Kim HZ, Hwang SI, Lee JE, Oh N, Jung K, Kim M, Kim KE, Kim H, Lim NK, Jeon CJ, Lee GM, Jeon BH, Nam DH, Sung HK, Nagy A, Yoo OJ, Koh GY. Double antiangiogenic protein, DAAP, targeting VEGF-A and angiopoietins in tumor angiogenesis, metastasis, and vascular leakage. Cancer Cell 2010. 9;18(2):171-184.

Samavarchi-Tehrani P, Golipour A, David L, Sung HK, Beyer TA, Datti A, Woltjen K, Nagy A, Wrana JL. Functional genomics reveals a BMP-driven mesenchymal-to-epithelial transition in the initiation of somatic cell reprogramming. Cell Stem Cell 2010. 2:7(1):64-77

Sung HK, Michael IP, Nagy A. Multifaceted role of vascular endothelial growth factor signaling in adult tissue physiology: an emerging concept with clinical implications. Curr Opin Hematol. 2010. 17(3): 206-12.

Sung HK, Kim YW, Choi SJ, Kim JY, Jeune KH, Won KC, Kim JK, Koh GY, Park SY. COMP-angiopoietin-1 enhances skeletal muscle blood flow and insulin sensitivity in mice. Am J Physiol Endocrinol Meta. 2009. 297: E402-409

Woltjen K, Michael IP, Mohseni P, Desai R, Mileikovsky M, Hamalainen R, Cowling R, Wang W, Liu P, Gertsenstein M, Kaji K, Sung HK, Nagy A. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 2009. 458, 766-770