Joey V. Barnett, Ph.D.
Acting Chair, Department of Pharmacology
Professor of Medicine (Clinical Pharmacology),
Professor of Pharmacology, Professor of Pediatrics,
Professor of Pathology, Microbiology & Immunology
Vanderbilt University Medical Center
460B Preston Building
Nashville, TN 37232
The goal of our laboratory is to determine the common mechanisms by which growth factors mediate and influence organ formation during embryogenesis. We have a special interest in heart formation in the chick and currently focus on the Transforming Growth Factor-beta (TGF beta) family of peptide growth factors in atrioventricular (AV) cushion transformation and coronary vessel formation in the heart. Localized epithelial-mesenchymal transformation in specific regions of the heart, including the AV cushion and proepicardium, gives rise to the valves and membranous septa of the heart and coronary vessels, respectively. Using specific antibodies to immunolocalize TGF beta receptor types and to block specific receptor types in an in vitro model of AV cushion transformation, we have identified the TGF beta receptor complex that mediates transformation. Further, misexpression of components of this complex by viral gene transfer converts normally unresponsive ventricular endocardial cells to transforming cells confirming the roles of specific receptors and downstream signaling molecules. Experiments in the proepicardium indicate the TGF beta receptors play a similar role in coronary vessel formation. Future experiments are designed to identify downstream components of receptor signaling and examine the role of this signaling complex in other sites in the embryo. In addition, a number of strategies are being used to identify genes expressed by the AV cushion, developing valves, and proepicardium. Finally, conditionally null mice are being generated to confirm and extend these results in mammals. These concerted strategies are directed at determining the role that growth factors, like TGF beta, play in organ formation during embryogenesis.
- Yuasa, M, Mignemi, NA, Nyman, JS, Duvall, CL, Schwartz, HS, Okawa, A, Yoshii, T, Bhattacharjee, G, Zhao, C, Bible, JE, Obremskey, WT, Flick, MJ, Degen, JL, Barnett, JV, Cates, JM, Schoenecker, JG Fibrinolysis is essential for fracture repair and prevention of heterotopic ossification. J Clin Invest, 125(8), 3117-31, 2015.
- Huang, T, Barnett, JV, Camenisch, TD Cardiac Epithelial-Mesenchymal Transition Is Blocked by Monomethylarsonous Acid (III). Toxicol Sci, 142(1), 225-38, 2014.
- Sidorova, TN, Mace, LC, Wells, KS, Yermalitskaya, LV, Su, PF, Shyr, Y, Atkinson, JB, Fogo, AB, Prinsen, JK, Byrne, JG, Petracek, MR, Greelish, JP, Hoff, SJ, Ball, SK, Glabe, CG, Brown, NJ, Barnett, JV, Murray, KT Hypertension is associated with preamyloid oligomers in human atrium: a missing link in atrial pathophysiology. J Am Heart Assoc, 3(6), 2014.
- Sewell-Loftin, MK, Delaughter, DM, Peacock, JR, Brown, CB, Baldwin, HS, Barnett, JV, Merryman, WD Myocardial contraction and hyaluronic acid mechanotransduction in¿¿epithelial-to-mesenchymal transformation of endocardial cells. Biomaterials, 2014.
- Sidorova, TN, Mace, LC, Wells, KS, Yermalitskaya, LV, Su, PF, Shyr, Y, Byrne, JG, Petracek, MR, Greelish, JP, Hoff, SJ, Ball, SK, Glabe, CG, Brown, NJ, Barnett, JV, Murray, KT Quantitative Imaging of Preamyloid Oligomers, a Novel Structural Abnormality, in Human Atrial Samples. J Histochem Cytochem, 62(7), 479-487, 2014.
- Sidorova, TN, Yermalitskaya, LV, Mace, LC, Sam Wells, K, Boutaud, O, Prinsen, JK, Davies, SS, Jackson Roberts, L, Dikalov, SI, Glabe, CG, Amarnath, V, Barnett, JV, Murray, KT Reactive ¿¿-Ketoaldehydes Promote Protein Misfolding and Preamyloid Oligomer Formation in Rapidly-Activated Atrial Cells. J Mol Cell Cardiol, 2014.
- Kain, KH, Miller, JW, Jones-Paris, CR, Thomason, RT, Lewis, JD, Bader, DM, Barnett, JV, Zijlstra, A The chick embryo as an expanding experimental model for cancer and cardiovascular research. Dev Dyn, 243(2), 216-28, 2014.
- Jacobson, R, Mignemi, N, Rose, K, O''Rear, L, Sarilla, S, Hamm, HE, Barnett, JV, Verhamme, IM, Schoenecker, J The hyperglycemic byproduct methylglyoxal impairs anticoagulant activity through covalent adduction of antithrombin III. Thromb Res, 2014.
- Yuasa, M, Mignemi, NA, Barnett, JV, Cates, JM, Nyman, JS, Okawa, A, Yoshii, T, Schwartz, HS, Stutz, CM, Schoenecker, JG The temporal and spatial development of vascularity in a healing displaced fracture. Bone, 67208-21, 2014.
- Hill, CR, Jacobs, BH, Brown, CB, Barnett, JV, Goudy, SL The type III transforming growth factor beta receptor regulates vascular and osteoblast development during palatogenesis. Dev Dyn, 2014.
- Allison, P, Espiritu, D, Barnett, JV, Camenisch, TD Type III TGF¿¿ receptor and Src direct hyaluronan-mediated invasive cell motility. Cell Signal, 27(3), 453-459, 2014.
- Allison, P, Huang, T, Broka, D, Parker, P, Barnett, JV, Camenisch, TD Disruption of canonical TGF¿¿-signaling in murine coronary progenitor cells by low level arsenic. Toxicol Appl Pharmacol, 272(1), 147-53, 2013.
- DeLaughter, DM, Christodoulou, DC, Robinson, JY, Seidman, CE, Baldwin, HS, Seidman, JG, Barnett, JV Spatial transcriptional profile of the chick and mouse endocardial cushions identify novel regulators of endocardial EMT in vitro. J Mol Cell Cardiol, 59196-204, 2013.
- 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 TGFÎ² receptor to promote invasion. Cell Signal, 24(5), 1012-22, 2012.
- Townsend, TA, Robinson, JY, How, T, Delaughter, DM, Blobe, GC, Barnett, JV Endocardial cell epithelial-mesenchymal transformation requires Type III TGFÎ² receptor interaction with GIPC. Cellular Signaling, 24247-256, 2012.
- Zhang, HF, Lin, XH, Yang, H, Zhou, LC, Guo, YL, Barnett, JV, Guo, ZM Regulation of the Activity and Expression of Aryl Hydrocarbon Receptor by Ethanol in Mouse Hepatic Stellate Cells. Alcohol Clin Exp Res, 2012.
- SÃ¡nchez, NS, Barnett, JV TGFÎ² and BMP-2 regulate epicardial cell invasion via TGFÎ²R3 activation of the Par6/Smurf1/RhoA pathway. Cell Signal, 24(2), 539-48, 2012.
- Doetschman, T, Barnett, JV, Runyan, RB, Camenisch, TD, Heimark, RL, Granzier, HL, Conway, SJ, Azhar, M Transforming growth factor beta signaling in adult cardiovascular diseases and repair. Cell Tissue Res, 347(1), 203-23, 2012.
- Barnett, JV ". Ph.D. education for biomedical scientists in the United States. Proceedings, of the 6th ORPHEUS Conference." Turkish Journal of Biochemistry , (36), 9-12, 2011.
- Townsend, TA, Robinson, JY, Deig, CR, Hill, CR, Misfeldt, A, Blobe, GC, Barnett, JV BMP-2 and TGFÎ²2 Shared Pathways Regulate Endocardial Cell Transformation. Cells Tissues Organs, 2011.
- Lencinas, A, Tavares, AL, Barnett, JV, Runyan, RB Collagen gel analysis of epithelial-mesenchymal transition in the embryo heart: an in vitro model system for the analysis of tissue interaction, signal transduction, and environmental effects. Birth Defects Res C Embryo Today, 93(4), 298-311, 2011.
- SÃ¡nchez, NS, Hill, CR, Love, JD, Soslow, JH, Craig, E, Austin, AF, Brown, CB, Czirok, A, Camenisch, TD, Barnett, JV The cytoplasmic domain of TGFÎ²R3 through its interaction with the scaffolding protein, GIPC, directs epicardial cell behavior. Dev Biol, 2011.
- Delaughter, DM, Saint-Jean, L, Baldwin, HS, Barnett, JV What chick and mouse models have taught us about the role of the endocardium in congenital heart disease. Birth Defects Res A Clin Mol Teratol, 2011.
- Karunamuni, G, Yang, K, Doughman, YQ, Wikenheiser, J, Bader, D, Barnett, J, Austin, A, Parsons-Wingerter, P, Watanabe, M Expression of lymphatic markers during avian and mouse cardiogenesis. Anat Rec (Hoboken), 293(2), 259-70, 2010.
- Craig, EA, Parker, P, Austin, AF, Barnett, JV, Camenisch, TD Involvement of the MEKK1 signaling pathway in the regulation of epicardial cell behavior by hyaluronan. Cell Signal, 2010.
- Angel, PM, Nusinow, D, Brown, CB, Violette, K, Barnett, JV, Zang, B, Baldwin, HS, Caprioli, RM Networked-based Characterization of Extracellular Matrix Proteins from Adult Mouse Pulmonary and Aortic Valves. J Proteome Res, 2010.
- Frieden, LA, Townsend, TA, Vaught, DB, Delaughter, DM, Hwang, Y, Barnett, JV, Chen, J Regulation of heart valve morphogenesis by Eph receptor ligand, ephrin-A1. Dev Dyn, 239(12), 3226-34, 2010.
- Craig, EA, Austin, AF, Vaillancourt, RR, Barnett, JV, Camenisch, TD TGFÎ²2-mediated production of hyaluronan is important for the induction of epicardial cell differentiation and invasion. Exp Cell Res, 316(20), 3397-405, 2010.
- Kirkbride, KC, Townsend, TA, Bruinsma, MW, Barnett, JV, Blobe, GC Bone morphogenetic proteins signal through the transforming growth factor-beta type III receptor. J Biol Chem, 283(12), 7628-7637, 2008.
- Criswell, TL, Dumont, N, Barnett, JV, Arteaga, CL Knockdown of the transforming growth factor-beta type III receptor impairs motility and invasion of metastatic cancer cells. Cancer Res, 68(18), 7304-12, 2008.
- Austin, AF, Compton, LA, Love, JD, Brown, CB, Barnett, JV Primary and immortalized mouse epicardial cells undergo differentiation in response to TGFbeta. Dev Dyn, 237(2), 366-376, 2008.
- Townsend, TA, Wrana, JL, Davis, GE, Barnett, JV Transforming growth factor-beta-stimulated endocardial cell transformation is dependent on Par6c regulation of RhoA. J Biol Chem, 283(20), 13834-41, 2008.
- Compton, LA, Potash, DA, Brown, CB, Barnett, JV Coronary vessel development is dependent on the type III transforming growth factor beta receptor. Circ Res, 101(8), 784-91, 2007.
- Barnett, J Directors of Pharmacology Graduate Programs: Pharm Phorum. Mol Interv, 6(1), 4-7, 2006.
- Compton, LA, Potash, DA, Mundell, NA, Barnett, JV Transforming growth factor-beta induces loss of epithelial character and smooth muscle cell differentiation in epicardial cells. Dev Dyn, 235(1), 82-93, 2006.
- Olivey, HE, Mundell, NA, Austin, AF, Barnett, JV Transforming growth factor-beta stimulates epithelial-mesenchymal transformation in the proepicardium. Dev Dyn, 235(1), 50-9, 2006.
- Desgrosellier, JS, Mundell, NA, McDonnell, MA, Moses, HL, Barnett, JV Activin receptor-like kinase 2 and Smad6 regulate epithelial-mesenchymal transformation during cardiac valve formation. Dev Biol, 280(1), 201-10, 2005.
- Olivey, Harold E, Compton, Leigh A, Barnett, Joey V Coronary vessel development: the epicardium delivers. Trends Cardiovasc Med, 14(6), 247-51, 2004.
- Marlow, Michael S, Brown, Christopher B, Barnett, Joey V, Krezel, Andrzej M, Solution structure of the chick TGFbeta type II receptor ligand-binding domain.. J Mol Biol, 326989-97, 2003.
- Lai, Y T, Beason, K B, Brames, G P, Desgrosellier, J S, Cleggett, M C, Shaw, M V, Brown, C B, Barnett, J V Activin receptor-like kinase 2 can mediate atrioventricular cushion transformation. Dev Biol, 222(1), 1-11, 2000.
- Brown, C B, Boyer, A S, Runyan, R B, Barnett, J V Requirement of type III TGF-beta receptor for endocardial cell transformation in the heart. Science, 283(5410), 2080-2, 1999.