Charles C Hong, M.D., Ph.D.

Profile

Dr. Charles (Chaz) Hong is a physician-scientist with background in molecular biology, developmental biology, chemical biology, and cardiovascular genetics.  He is an Associate Professor of Cardiovascular Medicine, Pharmacology, and Cell and Developmental Biology, and a member of the Veterans Affairs Tennessee Valley Healthcare System.  He is also a member of the Vanderbilt Institute of Chemical Biology and the Vanderbilt Center for Stem Cell Biology.  

Dr. Hong received his MD-PhD with Honors from Yale, then completed cardiology fellowship at Massachusetts General Hospital, where he was a Schreyer Fellow, and postdoctoral fellowship at Harvard Medical School, where he was a Sarnoff Scholar. After a brief stint on the Harvard Medical School faculty, Dr. Hong came to Vanderbilt in 2006. 

RESERACH ACCOMPLISHMENTS:

• 2006 - Discovered the role of ERK/MAP kinase signaling in artery specification.
• 2008 - Discovered the first pharmacological inhibitor of the BMP pathway.
• 2010 - First large scale in vivo structure activity relationship (SAR) study outside the anti-microbial field.
• 2008, 2010 - First reported use of pharmacological inhibitors of BMP and Wnt pathways to induce cardiomyogenesis in pluripotent stem cells.
• 2011 - First report of the role of BMP signaling in cholesterol homeostasis.
• 2014 - First report of the therapeutic potential of BMP inhibitors for metastatic breast cancer.
• 2015 - Signed exclusive licensing and research agreement with La Jolla Pharmaceutical Co. for clinical development of technology developed in the Hong lab.

The Hong laboratory is focused on Chemical Biology of vertebrate development and stem cell differentiation.



1) Chemical Genetics of Embryonic Development: In a manner analogous to classic mutagenesis screens, we conduct high-throughput chemical screens using zebrafish to discover small molecules that specifically perturb embryonic pattern formation. Using the chemical genetic approach, incorporating molecular cell biology, embryology, biochemistry and medicinal chemistry, we have discovered exquisitely selective modulators of the Bone Morphogenetic Protein (BMP), Wnt, Innate Immunity and Hedgehog pathways, as well as important new signaling components that direct early vertebrate development.



2) Regenerative Chemical Biology: Since small molecules that perturb embryonic patterning do so by promoting development of specific cell and tissue types, we predict that they will be valuable chemical reagents for stem cell research and cell-based regenerative therapies. We have developed chemical methods for robust induction of neurogenesis and cardiomyogenesis in pluripotent stem cells.



3) Drug Discovery/ Experimental Therapeutics: Since aberrant activities of developmental pathways play major roles in pathogenesis of many adult diseases, we are exploring therapeutic potential of our novel small molecules for a number of human diseases.  For example, we have made key contributions to the elucidation of BMP signaling as a promising therapeutic target for anemia of chronic disease, heterotopic ossification syndromes, inflammatory bowel disease, and atherosclerosis.

Publications

The following timeline graph is generated from all co-authored publications.

1. Emerging roles of the bone morphogenetic protein pathway in cancer: potential therapeutic target for kinase inhibition. Jiramongkolchai P, Owens P, Hong CC (2016) Biochem Soc Trans 44(4): 1117-34
   › Primary publication · 27528760 (PubMed) · PMC5483997 (PubMed Central)
2. Development of thieno- and benzopyrimidinone inhibitors of the Hedgehog signaling pathway reveals PDE4-dependent and PDE4-independent mechanisms of action. Hempel JE, Cadar AG, Hong CC (2016) Bioorg Med Chem Lett 26(8): 1947-53
   › Primary publication · 26976215 (PubMed) · PMC5147493 (PubMed Central)
3. Human induced pluripotent stem cell (hiPSC) derived cardiomyocytes to understand and test cardiac calcium handling: A glass half full. Hwang HS, Kryshtal DO, Feaster TK, Sánchez-Freire V, Zhang J, Kamp TJ, Hong CC, Wu JC, Knollmann BC (2015) J Mol Cell Cardiol 89(Pt B): 379-80
   › Primary publication · 26695095 (PubMed)
4. Matrigel Mattress: A Method for the Generation of Single Contracting Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. Feaster TK, Cadar AG, Wang L, Williams CH, Chun YW, Hempel JE, Bloodworth N, Merryman WD, Lim CC, Wu JC, Knollmann BC, Hong CC (2015) Circ Res 117(12): 995-1000
   › Primary publication · 26429802 (PubMed) · PMC4670592 (PubMed Central)
5. Combinatorial polymer matrices enhance in vitro maturation of human induced pluripotent stem cell-derived cardiomyocytes. Chun YW, Balikov DA, Feaster TK, Williams CH, Sheng CC, Lee JB, Boire TC, Neely MD, Bellan LM, Ess KC, Bowman AB, Sung HJ, Hong CC (2015) Biomaterials : 52-64
   › Primary publication · 26204225 (PubMed) · PMC4550551 (PubMed Central)
6. An in vivo chemical genetic screen identifies phosphodiesterase 4 as a pharmacological target for hedgehog signaling inhibition. Williams CH, Hempel JE, Hao J, Frist AY, Williams MM, Fleming JT, Sulikowski GA, Cooper MK, Chiang C, Hong CC (2015) Cell Rep 11(1): 43-50
   › Primary publication · 25818300 (PubMed) · PMC4394042 (PubMed Central)
7. Inhibition of BMP signaling suppresses metastasis in mammary cancer. Owens P, Pickup MW, Novitskiy SV, Giltnane JM, Gorska AE, Hopkins CR, Hong CC, Moses HL (2015) Oncogene 34(19): 2437-49
   › Primary publication · 24998846 (PubMed) · PMC4689138 (PubMed Central)
8. Selective small molecule targeting β-catenin function discovered by in vivo chemical genetic screen. Hao J, Ao A, Zhou L, Murphy CK, Frist AY, Keel JJ, Thorne CA, Kim K, Lee E, Hong CC (2013) Cell Rep 4(5): 898-904
   › Primary publication · 24012757 (PubMed) · PMC3923627 (PubMed Central)
9. Whole exome sequencing identifies a causal RBM20 mutation in a large pedigree with familial dilated cardiomyopathy. Wells QS, Becker JR, Su YR, Mosley JD, Weeke P, D'Aoust L, Ausborn NL, Ramirez AH, Pfotenhauer JP, Naftilan AJ, Markham L, Exil V, Roden DM, Hong CC (2013) Circ Cardiovasc Genet 6(4): 317-26
   › Primary publication · 23861363 (PubMed) · PMC3895490 (PubMed Central)
10. Stem cell-derived cardiomyocytes as a tool for studying proarrhythmia: a better canary in the coal mine? Roden DM, Hong CC (2013) Circulation 127(16): 1641-3
    › Primary publication · 23519759 (PubMed) · PMC3954984 (PubMed Central)
11. Pharmacological suppression of hepcidin increases macrophage cholesterol efflux and reduces foam cell formation and atherosclerosis. Saeed O, Otsuka F, Polavarapu R, Karmali V, Weiss D, Davis T, Rostad B, Pachura K, Adams L, Elliott J, Taylor WR, Narula J, Kolodgie F, Virmani R, Hong CC, Finn AV (2012) Arterioscler Thromb Vasc Biol 32(2): 299-307
    › Primary publication · 22095982 (PubMed) · PMC3262074 (PubMed Central)
12. Application of small organic molecules reveals cooperative TGFβ and BMP regulation of mesothelial cell behaviors. Cross EE, Thomason RT, Martinez M, Hopkins CR, Hong CC, Bader DM (2011) ACS Chem Biol 6(9): 952-61
    › Primary publication · 21740033 (PubMed) · PMC3177035 (PubMed Central)
13. Distinct signalling pathways regulate sprouting angiogenesis from the dorsal aorta and the axial vein. Wiley DM, Kim JD, Hao J, Hong CC, Bautch VL, Jin SW (2011) Nat Cell Biol 13(6): 686-92
    › Primary publication · 21572418 (PubMed) · PMC3107371 (PubMed Central)
14. Regenerative chemical biology: current challenges and future potential. Ao A, Hao J, Hong CC (2011) Chem Biol 18(4): 413-24
    › Primary publication · 21513877 (PubMed) · PMC3082739 (PubMed Central)
15. Cardiac induction of embryonic stem cells by a small molecule inhibitor of Wnt/β-catenin signaling. Wang H, Hao J, Hong CC (2011) ACS Chem Biol 6(2): 192-7
    › Primary publication · 21077691 (PubMed) · PMC3076310 (PubMed Central)
16. sFRP2 suppression of bone morphogenic protein (BMP) and Wnt signaling mediates mesenchymal stem cell (MSC) self-renewal promoting engraftment and myocardial repair. Alfaro MP, Vincent A, Saraswati S, Thorne CA, Hong CC, Lee E, Young PP (2010) J Biol Chem 285(46): 35645-53
    › Primary publication · 20826809 (PubMed) · PMC2975189 (PubMed Central)
17. In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors. Hao J, Ho JN, Lewis JA, Karim KA, Daniels RN, Gentry PR, Hopkins CR, Lindsley CW, Hong CC (2010) ACS Chem Biol 5(2): 245-53
    › Primary publication · 20020776 (PubMed) · PMC2825290 (PubMed Central)
18. Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis in mice. Wang L, Harrington L, Trebicka E, Shi HN, Kagan JC, Hong CC, Lin HY, Babitt JL, Cherayil BJ (2009) J Clin Invest 119(11): 3322-8
    › Primary publication · 19809161 (PubMed) · PMC2769199 (PubMed Central)
19. Large-scale small-molecule screen using zebrafish embryos. Hong CC (2009) Methods Mol Biol : 43-55
    › Primary publication · 19347615 (PubMed)
20. BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, Hong DW, McManus PM, Katagiri T, Sachidanandan C, Kamiya N, Fukuda T, Mishina Y, Peterson RT, Bloch KD (2008) Nat Med 14(12): 1363-9
    › Primary publication · 19029982 (PubMed) · PMC2846458 (PubMed Central)
21. Role of crosstalk between phosphatidylinositol 3-kinase and extracellular signal-regulated kinase/mitogen-activated protein kinase pathways in artery-vein specification. Hong CC, Kume T, Peterson RT (2008) Circ Res 103(6): 573-9
    › Primary publication · 18796644 (PubMed) · PMC2768581 (PubMed Central)
22. Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells. Hao J, Daleo MA, Murphy CK, Yu PB, Ho JN, Hu J, Peterson RT, Hatzopoulos AK, Hong CC (2008) PLoS One 3(8): e2904
    › Primary publication · 18682835 (PubMed) · PMC2483414 (PubMed Central)
23. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Yu PB, Hong CC, Sachidanandan C, Babitt JL, Deng DY, Hoyng SA, Lin HY, Bloch KD, Peterson RT (2008) Nat Chem Biol 4(1): 33-41
    › Primary publication · 18026094 (PubMed) · PMC2727650 (PubMed Central)
24. Artery/vein specification is governed by opposing phosphatidylinositol-3 kinase and MAP kinase/ERK signaling. Hong CC, Peterson QP, Hong JY, Peterson RT (2006) Curr Biol 16(13): 1366-72
    › Primary publication · 16824925 (PubMed) · PMC1930149 (PubMed Central)
25. An unusual mosaic protein with a protease domain, encoded by the nudel gene, is involved in defining embryonic dorsoventral polarity in Drosophila. Hong CC, Hashimoto C (1995) Cell 82(5): 785-94
    › Primary publication · 7671306 (PubMed)

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