Neil Jonathan Freedman, MD

Professor of Medicine
Professor in Cell Biology
Campus mail 447 Clin & Res Labs, Durham, NC 27710
Phone (919) 684-6873
Email address neil.freedman@duke.edu

Our work focuses on atherosclerosis-related signal transduction and the genetic bases of atherosclerosis and vein graft failure, both in vitro and in vivo. We investigate the regulation of receptor protein tyrosine kinases by G protein-coupled receptor kinases (GRKs), and the role of GRKs and β-arrestins in atherosclerosis; the role of tumor necrosis factor and its receptors in atherosclerosis; and the role of the dual Rho-GEF kalirin in atherosclerosis. For in vivo modeling of atherosclerosis and neointimal hyperplasia, we use mouse carotid artery bypass grafting with either veins or arteries from gene-deleted or congenic wild type mice, as well as aortic atherosclerosis studies and bone marrow transplantation. To study receptor phosphorylation, signal transduction, and intracellular trafficking, we employ primary smooth muscle cells, endothelial cells, and macrophages derived from knockout mice or treated with RNA interference.

Key Words: atherosclerosis, G protein-coupled receptor kinases, arrestins, desensitization, phosphorylation, platelet-derived growth factor receptors, receptor protein tyrosine kinases, smooth muscle cells, neointimal hyperplasia, Rho-GEF.

In Their Words

Education and Training

  • 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

Publications

Freedman, NJ, and Shenoy, SK. "Regulation of inflammation by β-arrestins: Not just receptor tales." Cellular Signalling 41 (January 2018): 41-45. (Review)

PMID
28189586
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, no. 13 (November 2017): 1551-1559.

PMID
29048463
Full Text

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, no. 2 (August 2017): 136-150.

PMID
28559424
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, no. 5 (May 2016): 984-993.

PMID
27013612
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, no. 14 (April 2016): 7450-7464.

PMID
26839314
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)

PMID
27378762
Full Text

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 inflammation." The Journal of Clinical Investigation 123, no. 10 (October 2013): 4232-4241.

PMID
23999430
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." The Journal of Clinical Investigation 123, no. 8 (August 2013): 3343-3352.

PMID
23863714
Full Text

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." Arteriosclerosis, Thrombosis, and Vascular Biology 33, no. 4 (April 2013): 702-708.

PMID
23288169
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, no. 5 (November 26, 2012): 817-830.

PMID
23166351
Full Text

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