Biomedical Research Education &
|S.B, Massachusetts Institute of Technology
Residency - Internal Medicine, Yale-New Haven Hospital
Fellowship - Cardiology, Massachusetts General Hospital
Post-doc, Harvard Medical School
Light Hall 1155A, 2215 Garland Ave.
Preston Research Building 383 37232
Chemical biology, Cardiovascular development, Drug discovery, Zebrafish, Developmental biology, Molecular medicine, Pharmacology, Stem cells, Inherited heart diseases, Regenerative Medicine, Induced pluripotent stem cells (iPSCs).,Cancer,Cardiac function,Developmental biology,Genetics,Heart,Human Genetics,Kinase,Pharmacology,Signal transduction,Stem cells
inherited heart disease, fibrodysplasia ossificans progressiva
Adult cardiovascular medicine
Our research can be divided into 2 broad areas. The first area involves chemical biology of vertebrate development, which entails discovery of small molecules that selectively modulate cell signaling pathways involved in embryogenesis. Since developmental pathways represent important untapped therapeutic targets, we have an active medicinal chemistry program to develop our novel small molecules as lead compounds for future therapies. We have thus far discovered potent and highly selective chemical modifiers of bone morphogenetic protein (BMP), Wnt, Hedgehog, and lipid signaling pathways, among others. Several of our compounds are first-in-class molecules with substantial therapeutic potential in rare and common diseases, including cancers, atherosclerosis, pulmonary hypertension and heart failure. Our chemical biology exploration has led to new opportunities for innovative therapeutic programs.
In the second, we are examining the utility of hiPSC to study human congenital heart diseases and inherited cardiomyopathies. Finally, we are developing human iPSC-derived cardiomyocytes as a platform for drug testing, including validation of novel cardiac inotropes.
2006 - Discovery of the role of PI3K and ERK signaling crosstalk in artery-vein specification.
2008 - Discovered dorsomorphin, 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 - Discovery of the role of BMP signaling in cholesterol homeostasis.
2013 - Identification of a mutation causing familial dilated cardiomyopathy by whole exome sequencing alone.
2014 - Discovery of the therapeutic potential of a BMP inhibitor for breast cancer metastasis.
The Center for Inherited Heart Disease collects clinical and genetic information that may help identify factors that influence cardiovascular disease progression and clinical outcomes in affected families. We also seek to discover new mutations that cause cardiovascular diseases. We maintain a repository of explanted human heart tissue samples as a resource for researchers. Our long-term goal is to help develop optimal "personalized care" for patients with familial cardiovascular diseases.
Inherited cardiovascular diseases, hypertrophic cardiomyopathy, idiopathic dilated cardiomyopathy, premature cardiac deaths, personalized genetic medicine.
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. Combinatorial polymer matrices enhance in vitro maturation of human induced pluripotent cell-derived cardiomyocytes. Biomaterials, 67, 52-64, 2015
Habib, A, Polavarapu, R, Karmali, V, Guo, L, Van Dam, R, Cheng, Q, Akahori, H, Saeed, O, Nakano, M, Pachura, K, Hong, CC, Shin, E, Kolodgie, F, Virmani, R, Finn, AV. Hepcidin-ferroportin axis controls toll-like receptor 4 dependent macrophage inflammatory responses in human atherosclerotic plaques. Atherosclerosis, 241(2), 692-700, 2015
Hempel, JE, Hong, CC. Practical strategies for small-molecule probe development in chemical biology. Methods Mol Biol, 1263, 209-23, 2015
Hempel, JE, Williams, CH, Hong, CC. Preface. Chemical biology. Methods Mol Biol, 1263, v, 2015
Hover, LD, Young, CD, Bhola, NE, Wilson, AJ, Khabele, D, Hong, CC, Moses, HL, Owens, P. Small molecule inhibitor of the bone morphogenetic protein pathway DMH1 reduces ovarian cancer cell growth. Cancer Lett, 2015
Hwang, HS, Kryshtal, DO, Feaster, TK, S??nchez-Freire, V, Zhang, J, Kamp, TJ, Hong, CC, Wu, JC, Knollmann, BC. Comparable calcium handling of human iPSC-derived cardiomyocytes generated by multiple laboratories. J Mol Cell Cardiol, 85, 79-88, 2015
Wang, X, Chun, YW, Zhong, L, Chiusa, M, Balikov, DA, Frist, AY, Lim, CC, Maltais, S, Bellan, L, Hong, CC*, Sung, HJ* *Co-corresponding authors. A temperature-sensitive, self-adhesive hydrogel to deliver iPSC-derived cardiomyocytes for heart repair. Int J Cardiol, 190, 177-180, 2015
Williams, CH, Hempel, JE, Hao, J, Frist, AY, Williams, MM, Fleming, JT, Sulikowski, GA, Cooper, MK, Chiang, C, Hong, CC. An In??Vivo Chemical Genetic Screen Identifies Phosphodiesterase 4 as a Pharmacological Target for Hedgehog Signaling Inhibition. Cell Rep, 11, 43-50, 2015
Williams, CH, Hong, CC. High content screening for modulators of cardiovascular or global developmental pathways in zebrafish. Methods Mol Biol, 1263, 167-74, 2015
Aboud, AA, Tidball, AM, Kumar, KK, Neely, MD, Han, B, Ess, KC, Hong, CC, Erikson, KM, Hedera, P, Bowman, AB. PARK2 patient neuroprogenitors show increased mitochondrial sensitivity to copper. Neurobiol Dis, 73C, 204-212, 2014
Fotinos, A, Nagarajan, N, Martins, AS, Fritz, DT, Garsetti, D, Lee, AT, Hong, CC, Rogers, MB. Bone Morphogenetic Protein-focused Strategies to Induce Cytotoxicity in Lung Cancer Cells. Anticancer Res, 34(5), 2095-104, 2014
Owens, P, Pickup, MW, Novitskiy, SV, Giltnane, JM, Gorska, AE, Hopkins, CR, Hong, CC*, Moses, HL.* *Co-senior authors. Inhibition of BMP signaling suppresses metastasis in mammary cancer. Oncogene, 2014
Talati, M, West, J, Zaynagetdinov, R, Hong, CC, Han, W, Blackwell, T, Robinson, L, Blackwell, TS, Lane, K. BMP Pathway Regulation of and by Macrophages. PLoS One, 9(4), e94119, 2014
Tsugawa, D, Oya, Y, Masuzaki, R, Ray, K, Engers, DW, Dib, M, Do, N, Kuramitsu, K, Ho, K, Frist, A, Yu, PB, Bloch, KD, Lindsley, CW, Hopkins, CR, Hong, CC, Karp, SJ. Specific activin receptor-like kinase 3 inhibitors enhance liver regeneration. J Pharmacol Exp Ther, 351(3), 549-58, 2014
West, JD, Austin, ED, Gaskill, C, Marriott, S, Baskir, R, Bilousova, G, Jean, JC, Hemnes, AR, Menon, S, Bloodworth, NC, Fessel, JP, Kropski, JA, Irwin, DC, Ware, LB, Wheeler, LA, Hong, CC, Meyrick, BO, Loyd, JE, Bowman, AB, Ess, KC, Klemm, DJ, Young, PP, Merryman, WD, Kotton, D, Majka, SM. Identification of a Common Wnt Associated Genetic Signature Across Multiple Cell Types in Pulmonary Arterial Hypertension. Am J Physiol Cell Physiol, 2014
Yang, T, Chun, YW, Stroud, DM, Mosley, JD, Knollmann, BC, Hong, CC, Roden, DM. Screening for Acute IKr Block is Insufficient to Detect Torsades de Pointes Liability: Role of Late Sodium Current. Circulation, 2014
Hopkins, CR. Development of a potent and ALK2 selective bone morphogenetic protein receptor (BMP) inhibitor. Probe Reports from the NIH Molecular Libraries Program, 2013
Engers, DW, Frist, AY, Lindsley, CW, Hong, CC, Hopkins, CR. Synthesis and structure-activity relationships of a novel and selective bone morphogenetic protein receptor (BMP) inhibitor derived from the pyrazolo[1.5-a]pyrimidine scaffold of Dorsomorphin: The discovery of ML347 as an ALK2 versus ALK3 selective MLPCN probe. Bioorg Med Chem Lett, 23(11), 3248-52, 2013
Hao, J, Ao, A, Zhou, L, Murphy, CK, Frist, AY, Keel, JJ, Thorne, CA, Kim, K, Lee, E, Hong, CC. Selective Small Molecule Targeting ??-Catenin Function Discovered by In??Vivo Chemical Genetic Screen. Cell Rep, 4, 107, 2013
Owens, P, Polikowsky, H, Pickup, MW, Gorska, AE, Jovanovic, B, Shaw, AK, Novitskiy, SV, Hong, CC, Moses, HL. Bone morphogenetic proteins stimulate mammary fibroblasts to promote mammary carcinoma cell invasion. PLoS One, 8(6), e67533, 2013
Roden, DM, Hong, CC. Stem cell-derived cardiomyocytes as a tool for studying proarrhythmia: a better canary in the coal mine. Circulation, 127(16), 1641-3, 2013
Shelton, EL, Galindo, CL, Williams, CH, Pfaltzgraff, E, Hong, CC, Bader, DM. Autotaxin signaling governs phenotypic heterogeneity in visceral and parietal mesothelia. PLoS One, 8(7), e69712, 2013
Hong CC. Chemically induced pluripotent stem cells (CiPSC): a potential chemical biological breakthrough in reprogramming? . Chemical Biology in Regenerative Medicine: Bridging Stem Cells and Future Therapies, 2013
Hong, CC. Pluripotent Stem Cells for Modeling Human Cardiovascular Diseases. Pluripotent Stem Cells, Chap. 20, 439-457, 2013
Sun, CC, Vaja, V, Chen, S, Theurl, I, Stepanek, A, Brown, DE, Cappellini, MD, Weiss, G, Hong, CC, Lin, HY, Babitt, JL. A hepcidin lowering agent mobilizes iron for incorporation into red blood cells in an adenine-induced kidney disease model of anemia in rats. Nephrol Dial Transplant, 28, 1733-43, 2013
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. Whole Exome Sequencing Identifies a Causal RBM20 Mutation in a Large Pedigree with Familial Dilated Cardiomyopathy. Circ Cardiovasc Genet, 6, 317-326, 2013
Williams, C, Hong, C. Making Models Work: Library Annotation through Phenoclustering. Drug Discov Today Dis Models, 10(1), 2013
Ao, A, Hao, J, Hopkins, CR, Hong, CC. DMH1, a Novel BMP Small Molecule Inhibitor, Increases Cardiomyocyte Progenitors and Promotes Cardiac Differentiation in Mouse Embryonic Stem Cells. PLoS One, 7(7), e41627, 2012
Hill, CR, Sanchez, NS, Love, JD, Arrieta, JA, Hong, CC, Brown, CB, Austin, AF, Barnett, JV. BMP2 signals loss of epithelial character in epicardial cells but requires the Type III TGFI? receptor to promote invasion. Cell Signal, 24(5), 1012-22, 2012
Neely, MD, Litt, MJ, Tidball, AM, Li, GG, Aboud, AA, Hopkins, CR, Chamberlin, R, Hong, CC, Ess, KC, Bowman, AB. DMH1, a Highly Selective Small Molecule BMP Inhibitor Promotes Neurogenesis of hiPSCs: Comparison of PAX6 and SOX1 Expression during Neural Induction. ACS Chem Neurosci, 3(6), 482-91, 2012
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* (*Co-corresponding authors). Pharmacological suppression of hepcidin increases macrophage cholesterol efflux and reduces foam cell formation and atherosclerosis. Arterioscler Thromb Vasc Biol, 32(2), 299-307, 2012
Sheng, CC, Hong, CC. Mixing of the old with the new: nanoparticle-mediated pioglitazone delivery to enhance therapeutic neovascularization. Arterioscler Thromb Vasc Biol, 32(10), 2337-8, 2012
Wang, L, Trebicka, E, Fu, Y, Ellenbogen, S, Hong, CC, Babitt, JL, Lin, HY, Cherayil, BJ. The bone morphogenetic protein-hepcidin axis as a therapeutic target in inflammatory bowel disease. Inflamm Bowel Dis, 18(1), 112-9, 2012 PMCID:3046139
Ao, A, Hao, J, Hong, CC. Regenerative chemical biology: current challenges and future potential. Chem Biol, 18(4), 413-24, 2011 PMCID:3127116
Ao, A, Williams, CH, Hao, J, Hong, CC. Modified mouse embryonic stem cell based assay for quantifying cardiogenic induction efficiency. J Vis Exp(50), 2011 PMCID:3169258
Gupta, MK, Walthall, JM, Venkataraman, R, Crowder, SW, Jung, DK, Yu, SS, Feaster, TK, Wang, X, Giorgio, TD, Hong, CC, Baudenbacher, FJ, Hatzopoulos, AK, Sung, HJ. Combinatorial polymer electrospun matrices promote physiologically-relevant cardiomyogenic stem cell differentiation. PLoS One, 6(12), e28935, 2011 PMCID:3246450
Hao, J, Sawyer, DB, Hatzopoulos, AK, Hong, CC. Recent Progress on Chemical Biology of Pluripotent Stem Cell Self-renewal, Reprogramming and Cardiomyogenesis. Rec Pat Regen Med, 1(3), 263-274, 2011
Hao, J, Zhou, L, Hong, CC. Chemical biology of pluripotent stem cells: focus on cardiomyogenesis. Embryonic Stem Cells, Chap 3, 51-64, 2011
Meynard, D, Vaja, V, Sun, CC, Corradini, E, Chen, S, L??pez-Ot?-n, C, Grgurevic, L, Hong, CC, Stirnberg, M, G??tschow, M, Vukicevic, S, Babitt, JL, Lin, HY. Regulation of TMPRSS6 by BMP6 and iron in human cells and mice. Blood, 118(3), 747-56, 2011 PMCID:3127116
Palmisano, BT, Rottman, JN, Wells, QS, DiSalvo, TG, Hong, CC. Familial evaluation for diagnosis of arrhythmogenic right ventricular dysplasia. Cardiology, 119(1), 47-53, 2011
Shi, S, Hoogaars, WM, de Gorter, DJ, van Heiningen, SH, Lin, HY, Hong, CC, Kemaladewi, DU, Aartsma-Rus, A, ten Dijke, P, ''t Hoen, PA. BMP antagonists enhance myogenic differentiation and ameliorate the dystrophic phenotype in a DMD mouse model. Neurobiol Dis, 41(2), 353-60, 2011 PMCID:3046139
The International Clinical Consortium on FOP (Hong, CC, contributing member) . The medical management of Fibrodysplasia Ossificans Progressiva: current management considerations. Clin Proc Intl Clin Consort FOP(3), 1-100, 2011
Theurl, I, Schroll, A, Sonnweber, T, Nairz, M, Theurl, M, Willenbacher, W, Eller, K, Wolf, D, Seifert, M, Sun, CC, Babitt, JL, Hong, CC, Menhall, T, Gearing, P, Lin, HY, Weiss, G. Pharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats. Blood, 118(18), 4977-84, 2011 PMCID:3127116
Wang, H, Hao, J, Hong, CC. Cardiac induction of embryonic stem cells by a small molecule inhibitor of Wnt/I?-catenin signaling. ACS Chem Biol, 6(2), 192-7, 2011 PMCID:3046139
Wells, QS, Ausborn, NL, Funke, BH, Pfotenhauer, JP, Fredi, JL, Baxter, S, Disalvo, TD, Hong, CC. Familial dilated cardiomyopathy associated with congenital defects in the setting of a novel VCL mutation (Lys815Arg) in conjunction with a known MYPBC3 variant. Cardiogenetics, 1(1), 2011
Wiley, DM, Kim, JD, Hao, J, Hong, CC, Bautch, VL, Jin, SW. Distinct signalling pathways regulate sprouting angiogenesis from the dorsal aorta and the axial vein. Nat Cell Biol, 13(6), 686-92, 2011 PMCID:3127116
Williams, CH, Hong, CC. Multi-step usage of in vivo models during rational drug design and discovery. Int J Mol Sci, 12(4), 2262-74, 2011 PMCID:3127116
Xia, Y, Cortez-Retamozo, V, Niederkofler, V, Salie, R, Chen, S, Samad, TA, Hong, CC, Arber, S, Vyas, JM, Weissleder, R, Pittet, MJ, Lin, HY. Dragon (repulsive guidance molecule b) inhibits IL-6 expression in macrophages. J Immunol, 186(3), 1369-76, 2011 PMCID:3046139
Alfaro, MP, Vincent, A, Saraswati, S, Thorne, CA, Hong, CC, Lee, E, Young, PP. sFRP2 suppression of bone morphogenic protein (BMP) and Wnt signaling mediates mesenchymal stem cell (MSC) self-renewal promoting engraftment and myocardial repair. J Biol Chem, 285(46), 35645-53, 2010 PMCID:3012377
Hao J, Daleo MA, Hong CC. Crosstalk between mitogen-activated protein kinase and phosphoinositide-3 kinase signaling pathways in development and disease. Systems Biology for Signaling Network, Ed. Choi S., Springer, New York, Ch 21, 505-529, 2010
Hao, J, Ho, JN, Lewis, JA, Karim, KA, Daniels, RN, Gentry, PR, Hopkins, CR, Lindsley, CW, Hong, CC. In vivo structure-activity relationship study of dorsomorphin analogues identifies selective VEGF and BMP inhibitors. ACS Chem Biol, 5(2), 245-53, 2010 PMCID:2827548
Hao, J, Williams, CH, Webb, ME, Hong, CC. Large scale zebrafish-based in vivo small molecule screen. J Vis Exp(46), 2010 PMCID:3127116
Harris, B, Pfotenhauer, JP, Silverstein, CA, Markham, LW, Schafer, K, Exil, VJ, Hong, CC. Serial observations and mutational analysis of an adoptee with family history of hypertrophic cardiomyopathy. Cardiol Res Pract, 2010, 697269, 2010 PMCID:2838361
Kaplan, FS, Zasloff, MA, Kitterman, JA, Shore, EM, Hong, CC, Rocke, DM. Early mortality and cardiorespiratory failure in patients with fibrodysplasia ossificans progressiva. J Bone Joint Surg Am, 92(3), 686-91, 2010 PMCID:2827548
Xia, Y, Babitt, JL, Bouley, R, Zhang, Y, Da Silva, N, Chen, S, Zhuang, Z, Samad, TA, Brenner, GJ, Anderson, JL, Hong, CC, Schneyer, AL, Brown, D, Lin, HY. Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells. J Am Soc Nephrol, 21(4), 666-77, 2010 PMCID:2827548
Hong, CC. Large-scale small-molecule screen using zebrafish embryos. Methods Mol Biol, 486, 43-55, 2009
Hong, CC, Yu, PB. Applications of small molecule BMP inhibitors in physiology and disease. Cytokine Growth Factor Rev, 20(5-6), 409-18, 2009 PMCID:2838361
Wang, L, Harrington, L, Trebicka, E, Shi, HN, Kagan, JC, Hong, CC, Lin, HY, Babitt, JL, Cherayil, BJ. Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis in mice. J Clin Invest, 119(11), 3322-8, 2009 PMCID:2769199
Hao, J, Daleo, MA, Murphy, CK, Yu, PB, Ho, JN, Hu, J, Peterson, RT, Hatzopoulos, AK, Hong, CC. Dorsomorphin, a selective small molecule inhibitor of BMP signaling, promotes cardiomyogenesis in embryonic stem cells. PLoS ONE, 3(8), e2904, 2008 PMCID:2483414
Hong, CC, Kume, T, Peterson, RT. Role of crosstalk between phosphatidylinositol 3-kinase and extracellular signal-regulated kinase/mitogen-activated protein kinase pathways in artery-vein specification. Circ Res, 103(6), 573-9, 2008 PMCID:2768581
The International Clinical Consortium on FOP (Hong, CC, contributing member). The medical management of Fibrodysplasia Ossificans Progressiva: current management considerations. Clin Proc Intl Clin Consort FOP, 3, 1-82, 2008
Yu, PB*, Hong, CC*, Sachidanandan, C, Babitt, JL, Deng, DY, Hoyng, SA, Lin, HY, Bloch, KD, Peterson, RT (*co-first authors). Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol, 4(1), 33-41, 2008 PMCID:2727650
Yu, PB, Deng, DY, Beppu, H, Hong, CC, Lai, C, Hoyng, SA, Kawai, N, Bloch, KD. Bone morphogenetic protein (BMP) type II receptor is required for BMP-mediated growth arrest and differentiation in pulmonary artery smooth muscle cells. J Biol Chem, 283(7), 3877-88, 2008 PMCID:2570262
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. BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med, 14(12), 1363-9, 2008 PMCID:2846458
Hong, CC, Peterson, QP, Hong, JY, Peterson, RT. Artery/vein specification is governed by opposing phosphatidylinositol-3 kinase
and MAP kinase/ERK signaling. Curr Biol, 16(13), 1366-72, 2006 PMCID:1930149
LeMosy, EK, Hong, CC, Hashimoto, C. Signal transduction by a protease cascade. Trends Cell Biol, 9(3), 102-7, 1999
Hong, CC, Hashimoto, C. The maternal nudel protein of Drosophila has two distinct roles important for
embryogenesis. Genetics, 143(4), 1653-61, 1996 PMCID:1207428
Hong, CC, Hashimoto, C. An unusual mosaic protein with a protease domain, encoded by the nudel gene,
is involved in defining embryonic dorsoventral polarity in Drosophila. Cell, 82(5), 785-94, 1995
de la Monte, SM, Quertermous, T, Hong, CC, Bloch, KD. Regional and maturation-associated expression of endothelin 2 in rat gastrointestinal
tract. J Histochem Cytochem, 43(2), 203-9, 1995
Cicila, GT, Rapp, JP, Bloch, KD, Kurtz, TW, Pravenec, M, Kren, V, Hong, CC, Quertermous, T, Ng, SC. Cosegregation of the endothelin-3 locus with blood pressure and relative heart
weight in inbred Dahl rats. J Hypertens, 12(6), 643-51, 1994
Bloch, KD, Hong, CC, Eddy, RL, Shows, TB, Quertermous, T. cDNA cloning and chromosomal assignment of the endothelin 2 gene: vasoactive
intestinal contractor peptide is rat endothelin 2. Genomics, 10(1), 236-42, 1991