Neil Jonathan Freedman, MD

Associate Professor of Medicine
Assistant 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

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, no. 8 (August 2013): 3343-3352.

PMID
23863714
Full Text

Wu, JH, 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, no. 4 (April 2013): 702-708.

PMID
23288169
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 infammation." Journal of Clinical Investigation 123, no. 10 (2013): 4232-4241.

PMID
23999430
Full Text

Han, SO, Xiao, K, Kim, J, Wu, JH, 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

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, no. 5 (November 2012): 1390-1397.

PMID
22796120
Full Text

Wu, JH, 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, no. 2 (February 2012): 308-316.

PMID
22095977
Full Text

Brown, MA, Zhang, L, Levering, VW, Wu, JH, 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, no. 11 (November 2010): 2150-2155.

PMID
20798381
Full Text

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, no. 1 (September 2010): 63-69.

PMID
20451204
Full Text

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, no. 14 (July 15, 2010): 2754-2766.

PMID
20421368
Full Text

Cai, X, Wu, JH, 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, no. 3 (March 2009): 626-636.

PMID
19092051
Full Text

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