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.

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

Zhang, Lisheng, Jiao-Hui Wu, Tai-Qin Huang, Igor Nepliouev, Leigh Brian, Zhushan Zhang, Virginia Wertman, et al. “Drebrin regulates angiotensin II-induced aortic remodelling..” Cardiovasc Res 114, no. 13 (November 1, 2018): 1806–15. https://doi.org/10.1093/cvr/cvy151.

PMID
29931051
Full Text

Jean-Charles, Pierre-Yves, Jiao-Hui Wu, Lisheng Zhang, Suneet Kaur, Igor Nepliouev, Jonathan A. Stiber, Leigh Brian, et al. “USP20 (Ubiquitin-Specific Protease 20) Inhibits TNF (Tumor Necrosis Factor)-Triggered Smooth Muscle Cell Inflammation and Attenuates Atherosclerosis..” Arterioscler Thromb Vasc Biol 38, no. 10 (October 2018): 2295–2305. https://doi.org/10.1161/ATVBAHA.118.311071.

PMID
30354204
Full Text

Zhang, Lisheng, Jiao-Hui Wu, James C. Otto, Susan B. Gurley, Elizabeth R. Hauser, Sudha K. Shenoy, Karim Nagi, et al. “Interleukin-9 mediates chronic kidney disease-dependent vein graft disease: a role for mast cells..” Cardiovasc Res 113, no. 13 (November 1, 2017): 1551–59. https://doi.org/10.1093/cvr/cvx177.

PMID
29048463
Full Text

Smith, Jeffrey S., Priya Alagesan, Nimit K. Desai, Thomas F. Pack, Jiao-Hui Wu, Asuka Inoue, Neil J. Freedman, and Sudarshan Rajagopal. “C-X-C Motif Chemokine Receptor 3 Splice Variants Differentially Activate Beta-Arrestins to Regulate Downstream Signaling Pathways..” Mol Pharmacol 92, no. 2 (August 2017): 136–50. https://doi.org/10.1124/mol.117.108522.

PMID
28559424
Full Text

Stiber, Jonathan A., Jiao-Hui Wu, Lisheng Zhang, Igor Nepliouev, Zhu-Shan Zhang, Victoria G. Bryson, Leigh Brian, et al. “The Actin-Binding Protein Drebrin Inhibits Neointimal Hyperplasia..” Arterioscler Thromb Vasc Biol 36, no. 5 (May 2016): 984–93. https://doi.org/10.1161/ATVBAHA.115.306140.

PMID
27013612
Full Text

Jean-Charles, Pierre-Yves, Lisheng Zhang, Jiao-Hui Wu, Sang-Oh Han, Leigh Brian, Neil J. Freedman, and Sudha K. Shenoy. “Ubiquitin-specific Protease 20 Regulates the Reciprocal Functions of β-Arrestin2 in Toll-like Receptor 4-promoted Nuclear Factor κB (NFκB) Activation..” J Biol Chem 291, no. 14 (April 1, 2016): 7450–64. https://doi.org/10.1074/jbc.M115.687129.

PMID
26839314
Full Text

Jean-Charles, P. -. Y., N. J. Freedman, and S. K. Shenoy. “Chapter Nine - Cellular Roles of Beta-Arrestins as Substrates and Adaptors of Ubiquitination and Deubiquitination..” Prog Mol Biol Transl Sci 141 (2016): 339–69. https://doi.org/10.1016/bs.pmbts.2016.04.003.

PMID
27378762
Full Text

Lu, Yuan, Lisheng Zhang, Xudong Liao, Panjamaporn Sangwung, Domenick A. Prosdocimo, Guangjin Zhou, Alexander R. Votruba, et al. “Kruppel-like factor 15 is critical for vascular inflammation..” J Clin Invest 123, no. 10 (October 2013): 4232–41. https://doi.org/10.1172/JCI68552.

PMID
23999430
Full Text

Chandra, Rashmi, Yu Wang, Rafiq A. Shahid, Steven R. Vigna, Neil J. Freedman, and Rodger A. Liddle. “Immunoglobulin-like domain containing receptor 1 mediates fat-stimulated cholecystokinin secretion..” J Clin Invest 123, no. 8 (August 2013): 3343–52. https://doi.org/10.1172/JCI68587.

PMID
23863714
Full Text

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