Scholars@Duke

• Background
• 

  Education, Training, & Certifications

  • Fellow in Cardiology, Medicine, Duke University 1990 - 1993
  • Visiting Scientist, Massachusetts Institute of Technology 1989 - 1990
  • Research Fellow in Medicine, Medicine, Brigham and Women's Hospital 1988 - 1989
  • Medical Resident, Medicine, Beth Israel Deaconess Medical Center 1985 - 1988
  • M.D., Harvard University 1985
• 

  Duke Appointment History

  • Assistant Professor in Cell Biology, Cell Biology, Basic Science Departments 2005 - 2017
  • Associate Professor of Medicine, Medicine, Cardiology, Medicine 2006 - 2017
  • Assistant Professor of Medicine, Medicine, Cardiology, Medicine 1996 - 2006
  • Associate in the Department of Medicine, Medicine, Cardiology, Medicine 1993 - 1996
• Research
• 

  Selected Grants

  • Mechanistic studies of Mas receptor activation and its role in aortic aneurysm formation awarded by National Institutes of Health 2017 - 2022
  • Multidisciplinary Heart and Vascular Diseases awarded by National Institutes of Health 1975 - 2021
  • Role of Drebrin in Atherosclerosis awarded by National Institutes of Health 2014 - 2019
  • Regulation of B-arrestin2's pro-atherogenic activity by the deubiquitinase USP20 awarded by National Institutes of Health 2014 - 2018
  • Role of Drebrin in Vascular Smooth Muscle Remodeling awarded by National Institutes of Health 2013 - 2018
  • Anti-atherogenic Mechanisms of the Dual Rho-GEF Kalirin awarded by National Institutes of Health 2014 - 2018
  • Desensitization of Vascular Receptor Tyrosine Kinases awarded by National Institutes of Health 2005 - 2012
  • Mechanisms of Arterial Wall-Mediated Atherogenesis awarded by National Institutes of Health 2005 - 2009
  • Aging, Atherosclerosis, and the Arterial Wall awarded by National Institutes of Health 2006 - 2009
  • Inflammation in Vein Graft Disease: A Genetic Approach awarded by National Institutes of Health 2004 - 2006
  • TNF-Inhibitor gene therapy for neointimal hyperplasia awarded by National Institutes of Health 2001 - 2005
  • Receptor Kinase Gene Therapy for Neointimal Hyperplasia awarded by National Institutes of Health 1999 - 2004
  • Receptor Kinase Gene Therapy for Neointimal Hyperplasia awarded by Department of Health and Human Services 1997 - 2001
  • Receptor Kinase Gene Therapy For Neointimal Hyperplasia awarded by National Institutes of Health 1997 - 1999
  • Receptor Desensitization In The Cardiovascular System awarded by National Institutes of Health 1994 - 1999
• Publications & Artistic Works
• 

  Selected Publications

  • Journal Articles

    • Freedman, NJ, and Shenoy, SK. "Regulation of inflammation by β-arrestins: Not just receptor tales." Cellular signalling 41 (January 2018): 41-45. (Review)  Full Text
    • Zhang, L, Wu, J-H, Otto, JC, Gurley, SB, Hauser, ER, Shenoy, SK, Nagi, K, Brian, L, Wertman, V, Mattocks, N, Lawson, JH, and Freedman, NJ. "Interleukin-9 mediates chronic kidney disease-dependent vein graft disease: a role for mast cells." Cardiovascular research 113.13 (November 2017): 1551-1559.  Full Text  Open Access Copy
    • Smith, JS, Alagesan, P, Desai, NK, Pack, TF, Wu, J-H, Inoue, A, Freedman, NJ, and Rajagopal, S. "C-X-C Motif Chemokine Receptor 3 Splice Variants Differentially Activate Beta-Arrestins to Regulate Downstream Signaling Pathways." Molecular pharmacology 92.2 (August 2017): 136-150.  Full Text
    • Stiber, JA, Wu, J-H, Zhang, L, Nepliouev, I, Zhang, Z-S, Bryson, VG, Brian, L, Bentley, RC, Gordon-Weeks, PR, Rosenberg, PB, and Freedman, NJ. "The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia." Arteriosclerosis, thrombosis, and vascular biology 36.5 (May 2016): 984-993.  Full Text
    • Jean-Charles, P-Y, Zhang, L, Wu, J-H, Han, S-O, Brian, L, Freedman, NJ, and Shenoy, SK. "Ubiquitin-specific Protease 20 Regulates the Reciprocal Functions of β-Arrestin2 in Toll-like Receptor 4-promoted Nuclear Factor κB (NFκB) Activation." The Journal of biological chemistry 291.14 (April 2016): 7450-7464.  Full Text
    • Jean-Charles, P-Y, Freedman, NJ, and Shenoy, SK. "Chapter Nine - Cellular Roles of Beta-Arrestins as Substrates and Adaptors of Ubiquitination and Deubiquitination." Progress in molecular biology and translational science 141 (January 2016): 339-369. (Review)  Full Text
    • Chandra, R, Wang, Y, Shahid, RA, Vigna, SR, Freedman, NJ, and Liddle, RA. "Immunoglobulin-like domain containing receptor 1 mediates fat-stimulated cholecystokinin secretion." J Clin Invest 123.8 (August 2013): 3343-3352.  Full Text  Link to Item
    • Wu, J-H, Fanaroff, AC, Sharma, KC, Smith, LS, Brian, L, Eipper, BA, Mains, RE, Freedman, NJ, and Zhang, L. "Kalirin promotes neointimal hyperplasia by activating Rac in smooth muscle cells." Arterioscler Thromb Vasc Biol 33.4 (April 2013): 702-708.  Full Text  Link to Item
    • Lu, Y, Zhang, L, Liao, X, Sangwung, P, Prosdocimo, DA, Zhou, G, Votruba, AR, Brian, L, Han, YJ, Gao, H, Wang, Y, Shimizu, K, Weinert-Stein, K, Khrestian, M, Simon, DI, Freedman, NJ, and Jain, MK. "Kruppel-like factor 15 is critical for vascular infammation." Journal of Clinical Investigation 123.10 (2013): 4232-4241.  Full Text
    • Han, S-O, Xiao, K, Kim, J, Wu, J-H, Wisler, JW, Nakamura, N, Freedman, NJ, and Shenoy, SK. "MARCH2 promotes endocytosis and lysosomal sorting of carvedilol-bound β(2)-adrenergic receptors." J Cell Biol 199.5 (November 26, 2012): 817-830.  Full Text  Link to Item
    • Zhang, L, Brian, L, and Freedman, NJ. "Vein graft neointimal hyperplasia is exacerbated by CXCR4 signaling in vein graft-extrinsic cells." J Vasc Surg 56.5 (November 2012): 1390-1397.  Full Text  Link to Item
    • Wu, J-H, Zhang, L, Fanaroff, AC, Cai, X, Sharma, KC, Brian, L, Exum, ST, Shenoy, SK, Peppel, K, and Freedman, NJ. "G protein-coupled receptor kinase-5 attenuates atherosclerosis by regulating receptor tyrosine kinases and 7-transmembrane receptors." Arterioscler Thromb Vasc Biol 32.2 (February 2012): 308-316.  Full Text  Link to Item
    • Brown, MA, Zhang, L, Levering, VW, Wu, J-H, Satterwhite, LL, Brian, L, Freedman, NJ, and Truskey, GA. "Human umbilical cord blood-derived endothelial cells reendothelialize vein grafts and prevent thrombosis." Arterioscler Thromb Vasc Biol 30.11 (November 2010): 2150-2155.  Full Text  Link to Item
    • Zhu, S, Malhotra, A, Zhang, L, Deng, S, Zhang, T, Freedman, NJ, Storms, R, Peppel, K, Goldschmidt-Clermont, PJ, and Dong, C. "Human umbilical cord blood endothelial progenitor cells decrease vein graft neointimal hyperplasia in SCID mice." Atherosclerosis 212.1 (September 2010): 63-69.  Full Text  Link to Item
    • Zhang, L, Connelly, JJ, Peppel, K, Brian, L, Shah, SH, Nelson, S, Crosslin, DR, Wang, T, Allen, A, Kraus, WE, Gregory, SG, Hauser, ER, and Freedman, NJ. "Aging-related atherosclerosis is exacerbated by arterial expression of tumor necrosis factor receptor-1: evidence from mouse models and human association studies." Hum Mol Genet 19.14 (July 15, 2010): 2754-2766.  Full Text  Link to Item
    • Cai, X, Wu, J-H, Exum, ST, Oppermann, M, Premont, RT, Shenoy, SK, and Freedman, NJ. "Reciprocal regulation of the platelet-derived growth factor receptor-beta and G protein-coupled receptor kinase 5 by cross-phosphorylation: effects on catalysis." Mol Pharmacol 75.3 (March 2009): 626-636.  Full Text  Link to Item
    • Shah, SH, Freedman, NJ, Zhang, L, Crosslin, DR, Stone, DH, Haynes, C, Johnson, J, Nelson, S, Wang, L, Connelly, JJ, Muehlbauer, M, Ginsburg, GS, Crossman, DC, Jones, CJH, Vance, J, Sketch, MH, Granger, CB, Newgard, CB, Gregory, SG, Goldschmidt-Clermont, PJ, Kraus, WE, and Hauser, ER. "Neuropeptide Y gene polymorphisms confer risk of early-onset atherosclerosis." PLoS Genet 5.1 (January 2009): e1000318-.  Full Text  Open Access Copy  Link to Item
    • Shenoy, SK, Xiao, K, Venkataramanan, V, Snyder, PM, Freedman, NJ, and Weissman, AM. "Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor." J Biol Chem 283.32 (August 8, 2008): 22166-22176.  Full Text  Link to Item
    • Kim, J, Zhang, L, Peppel, K, Wu, J-H, Zidar, DA, Brian, L, DeWire, SM, Exum, ST, Lefkowitz, RJ, and Freedman, NJ. "Beta-arrestins regulate atherosclerosis and neointimal hyperplasia by controlling smooth muscle cell proliferation and migration." Circ Res 103.1 (July 3, 2008): 70-79.  Full Text  Open Access Copy  Link to Item
    • Wang, L, Hauser, ER, Shah, SH, Seo, D, Sivashanmugam, P, Exum, ST, Gregory, SG, Granger, CB, Haines, JL, Jones, CJH, Crossman, D, Haynes, C, Kraus, WE, Freedman, NJ, Pericak-Vance, MA, Goldschmidt-Clermont, PJ, and Vance, JM. "Polymorphisms of the tumor suppressor gene LSAMP are associated with left main coronary artery disease." Ann Hum Genet 72.Pt 4 (July 2008): 443-453.  Full Text  Link to Item
    • Zhang, L, Sivashanmugam, P, Wu, J-H, Brian, L, Exum, ST, Freedman, NJ, and Peppel, K. "Tumor necrosis factor receptor-2 signaling attenuates vein graft neointima formation by promoting endothelial recovery." Arterioscler Thromb Vasc Biol 28.2 (February 2008): 284-289.  Full Text  Link to Item
    • Vinge, LE, Andressen, KW, Attramadal, T, Andersen, GØ, Ahmed, MS, Peppel, K, Koch, WJ, Freedman, NJ, Levy, FO, Skomedal, T, Osnes, J-B, and Attramadal, H. "Substrate specificities of g protein-coupled receptor kinase-2 and -3 at cardiac myocyte receptors provide basis for distinct roles in regulation of myocardial function." Mol Pharmacol 72.3 (September 2007): 582-591.  Full Text  Link to Item
    • Zhang, L, Peppel, K, Sivashanmugam, P, Orman, ES, Brian, L, Exum, ST, and Freedman, NJ. "Expression of tumor necrosis factor receptor-1 in arterial wall cells promotes atherosclerosis." Arterioscler Thromb Vasc Biol 27.5 (May 2007): 1087-1094.  Full Text  Link to Item
    • Wu, J-H, Goswami, R, Cai, X, Exum, ST, Huang, X, Zhang, L, Brian, L, Premont, RT, Peppel, K, and Freedman, NJ. "Regulation of the platelet-derived growth factor receptor-beta by G protein-coupled receptor kinase-5 in vascular smooth muscle cells involves the phosphatase Shp2." J Biol Chem 281.49 (December 8, 2006): 37758-37772.  Full Text  Link to Item
    • Freedman, NJ, and Ginsburg, GS. "Novel--and "neu"--therapeutic possibilities for heart failure." J Am Coll Cardiol 48.7 (October 3, 2006): 1448-1450.  Full Text  Link to Item
    • Cai, X, and Freedman, NJ. "New therapeutic possibilities for vein graft disease in the post-edifoligide era." Future Cardiol 2.4 (July 2006): 493-501.  Full Text  Link to Item
    • Wu, J-H, Goswami, R, Kim, LK, Miller, WE, Peppel, K, and Freedman, NJ. "The platelet-derived growth factor receptor-beta phosphorylates and activates G protein-coupled receptor kinase-2. A mechanism for feedback inhibition." J Biol Chem 280.35 (September 2, 2005): 31027-31035.  Full Text  Link to Item
    • Peppel, K, Zhang, L, Orman, ES, Hagen, P-O, Amalfitano, A, Brian, L, and Freedman, NJ. "Activation of vascular smooth muscle cells by TNF and PDGF: overlapping and complementary signal transduction mechanisms." Cardiovasc Res 65.3 (February 15, 2005): 674-682.  Full Text  Link to Item
    • Zhang, L, Peppel, K, Brian, L, Chien, L, and Freedman, NJ. "Vein graft neointimal hyperplasia is exacerbated by tumor necrosis factor receptor-1 signaling in graft-intrinsic cells." Arterioscler Thromb Vasc Biol 24.12 (December 2004): 2277-2283.  Full Text  Link to Item
    • Hildreth, KL, Wu, J-H, Barak, LS, Exum, ST, Kim, LK, Peppel, K, and Freedman, NJ. "Phosphorylation of the platelet-derived growth factor receptor-beta by G protein-coupled receptor kinase-2 reduces receptor signaling and interaction with the Na(+)/H(+) exchanger regulatory factor." J Biol Chem 279.40 (October 1, 2004): 41775-41782.  Full Text  Link to Item
    • Freedman, NJ, and Lefkowitz, RJ. "Anti-beta(1)-adrenergic receptor antibodies and heart failure: causation, not just correlation." J Clin Invest 113.10 (May 2004): 1379-1382. (Review)  Full Text  Open Access Copy  Link to Item
    • Zhang, L, Freedman, NJ, Brian, L, and Peppel, K. "Graft-extrinsic cells predominate in vein graft arterialization." Arterioscler Thromb Vasc Biol 24.3 (March 2004): 470-476.  Full Text  Link to Item
    • Wu, J-H, Peppel, K, Nelson, CD, Lin, F-T, Kohout, TA, Miller, WE, Exum, ST, and Freedman, NJ. "The adaptor protein beta-arrestin2 enhances endocytosis of the low density lipoprotein receptor." J Biol Chem 278.45 (November 7, 2003): 44238-44245.  Full Text  Link to Item
    • Freedman, NJ, Kim, LK, Murray, JP, Exum, ST, Brian, L, Wu, J-H, and Peppel, K. "Phosphorylation of the platelet-derived growth factor receptor-beta and epidermal growth factor receptor by G protein-coupled receptor kinase-2. Mechanisms for selectivity of desensitization." J Biol Chem 277.50 (December 13, 2002): 48261-48269.  Full Text  Link to Item
    • Peppel, K, Zhang, L, Huynh, TTT, Huang, X, Jacobson, A, Brian, L, Exum, ST, Hagen, P-O, and Freedman, NJ. "Overexpression of G protein-coupled receptor kinase-2 in smooth muscle cells reduces neointimal hyperplasia." J Mol Cell Cardiol 34.10 (October 2002): 1399-1409.  Link to Item
    • Zhang, L, Hagen, P-O, Kisslo, J, Peppel, K, and Freedman, NJ. "Neointimal hyperplasia rapidly reaches steady state in a novel murine vein graft model." J Vasc Surg 36.4 (October 2002): 824-832.  Link to Item
    • Liang, M, Freedman, NJ, Theiss, CT, and Liggett, SB. "Serine 232 of the alpha(2A)-adrenergic receptor is a protein kinase C-sensitive effector coupling switch." Biochemistry 40.49 (December 11, 2001): 15031-15037.  Link to Item
    • Peppel, K, Jacobson, A, Huang, X, Murray, JP, Oppermann, M, and Freedman, NJ. "Overexpression of G protein-coupled receptor kinase-2 in smooth muscle cells attenuates mitogenic signaling via G protein-coupled and platelet-derived growth factor receptors." Circulation 102.7 (August 15, 2000): 793-799.  Link to Item
    • Pitcher, JA, Freedman, NJ, and Lefkowitz, RJ. "G protein-coupled receptor kinases." Annu Rev Biochem 67 (1998): 653-692. (Review)  Full Text  Link to Item
    • Freedman, NJ, Ament, AS, Oppermann, M, Stoffel, RH, Exum, ST, and Lefkowitz, RJ. "Phosphorylation and desensitization of human endothelin A and B receptors. Evidence for G protein-coupled receptor kinase specificity." J Biol Chem 272.28 (July 11, 1997): 17734-17743.  Link to Item
    • Oppermann, M, Diversé-Pierluissi, M, Drazner, MH, Dyer, SL, Freedman, NJ, Peppel, KC, and Lefkowitz, RJ. "Monoclonal antibodies reveal receptor specificity among G-protein-coupled receptor kinases." Proc Natl Acad Sci U S A 93.15 (July 23, 1996): 7649-7654.  Open Access Copy  Link to Item
    • Oppermann, M, Freedman, NJ, Alexander, RW, and Lefkowitz, RJ. "Phosphorylation of the type 1A angiotensin II receptor by G protein-coupled receptor kinases and protein kinase C." J Biol Chem 271.22 (May 31, 1996): 13266-13272.  Link to Item
    • Freedman, NJ, and Lefkowitz, RJ. "Desensitization of G protein-coupled receptors." Recent Prog Horm Res 51 (1996): 319-351. (Review)  Link to Item
    • Pei, G, Kieffer, BL, Lefkowitz, RJ, and Freedman, NJ. "Agonist-dependent phosphorylation of the mouse delta-opioid receptor: involvement of G protein-coupled receptor kinases but not protein kinase C." Mol Pharmacol 48.2 (August 1995): 173-177.  Link to Item
    • Freedman, NJ, Liggett, SB, Drachman, DE, Pei, G, Caron, MG, and Lefkowitz, RJ. "Phosphorylation and desensitization of the human beta 1-adrenergic receptor. Involvement of G protein-coupled receptor kinases and cAMP-dependent protein kinase." J Biol Chem 270.30 (July 28, 1995): 17953-17961.  Link to Item
    • Barak, LS, Tiberi, M, Freedman, NJ, Kwatra, MM, Lefkowitz, RJ, and Caron, MG. "A highly conserved tyrosine residue in G protein-coupled receptors is required for agonist-mediated beta 2-adrenergic receptor sequestration." J Biol Chem 269.4 (January 28, 1994): 2790-2795.  Link to Item
    • Ishii, K, Chen, J, Ishii, M, Koch, WJ, Freedman, NJ, Lefkowitz, RJ, and Coughlin, SR. "Inhibition of thrombin receptor signaling by a G-protein coupled receptor kinase: Functional specificity among G-protein coupled receptor kinases." Journal of Biological Chemistry 269.2 (1994): 1125-1130.
    • Freedman, SF, Freedman, NJ, Shields, MB, Lobaugh, B, Samsa, GP, Keates, EU, and Ollie, A. "Effects of ocular carteolol and timolol on plasma high-density lipoprotein cholesterol level." Am J Ophthalmol 116.5 (November 15, 1993): 600-611.  Link to Item
    • Inglese, J, Freedman, NJ, Koch, WJ, and Lefkowitz, RJ. "Structure and mechanism of the G protein-coupled receptor kinases." J Biol Chem 268.32 (November 15, 1993): 23735-23738. (Review)  Link to Item
    • Liggett, SB, Freedman, NJ, Schwinn, DA, and Lefkowitz, RJ. "Structural basis for receptor subtype-specific regulation revealed by a chimeric β₃/β₂-adrenergic receptor." Proceedings of the National Academy of Sciences of the United States of America 90.8 (1993): 3665-3669.  Open Access Copy
    • Resnick, D, Freedman, NJ, Xu, S, and Krieger, M. "Secreted extracellular domains of macrophage scavenger receptors form elongated trimers which specifically bind crocidolite asbestos." Journal of Biological Chemistry 268.5 (1993): 3538-3545.
    • Freeman, M, Ekkel, Y, Rohrer, L, Penman, M, Freedman, NJ, Chisolm, GM, and Krieger, M. "Expression of type I and type II bovine scavenger receptors in Chinese hamster ovary cells: Lipid droplet accumulation and nonreciprocal cross competition by acetylated and oxidized low density lipoprotein." Proceedings of the National Academy of Sciences of the United States of America 88.11 (1991): 4931-4935.
    • Penman, M, Lux, A, Freedman, NJ, Rohrer, L, Ekkel, Y, McKinstry, H, Resnick, D, and Krieger, M. "The type I and type II bovine scavenger receptors expressed in chinese hamster ovary cells are trimeric proteins with collagenous triple helical domains comprising noncovalently associated monomers and cys⁸³-disulfide-linked dimers." Journal of Biological Chemistry 266.35 (1991): 23985-23993.
    • Newrock, KM, Freedman, N, Alfageme, CR, and Cohen, LH. "Isolation of sea urchin embryo histone H2Aα1 and immunological identification of other stage-specific H2A proteins." Developmental Biology 89.1 (January 1982): 248-253.  Full Text
• Teaching & Mentoring
• 

  Recent Courses

  • CELLBIO 493: Research Independent Study 2018
  • CVS 301B: RESEARCH IN CVS 2018

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