DEFINING TOMORROW'S VASCULAR STRATEGIES
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The Initiative

Prof. Alan Tall

Prof. Alan Tall
Columbia University
USA
 

Tilden Weger Bieler Professor of Medicine

 
Personal statement
 

Dr Tall's major research interest throughout his career has been on the metabolism and cellular effects of plasma high density lipoproteins (HDL). His earlier work focused on the role of the plasma lipid transfer proteins, CETP and PLTP, in regulating HDL metabolism. This was defined using genetic approaches in mice and humans, and led to the development of CETP inhibitors that are in clinical trials. Subsequent studies have focused on the role of the ATP binding cassette transporters, ABCA1 and ABCG1, in mediating cellular cholesterol efflux to HDL, and their impact of macrophage inflammation and atherogenesis. Recently this has led to an investigation of the role of ABCA1, ABCG1, apoE and HDL in regulating the proliferation of hematopoietic stem cells and the monocytosis and leukocytosis associated with atherosclerosis.

 
Position and Honors
 
1977 Assistant Professor of Medicine, Boston University
1978 - 1981 Assistant Professor of Medicine, Columbia University
1982 - 1989 Associate Professor of Medicine, Columbia University
1989 - Professor of Medicine, Columbia University
1998 - Tilden Weger Bieler Professor of Medicine, Columbia University
1990 - Head, Division of Molecular Medicine, Department of Medicine, Columbia University
1991 - 2006 Director, Columbia University SCOR in Arteriosclerosis and Molecular Medicine
2005 - Professor of Physiology & Cellular Biophysics
1983 - 1987 Member, Metabolism Study Section, NIH
1982 - 1984 American Society of Clinical Investigation
1990 - Association of American Physicians
1995 - 2000 Board of Scientific Counselors, NHLBI
1999 - 2000 Research Committee, AHA
1999 Irvine Page Award, ATVB Council, AHA
2011 Robert I. Levy Lecturer, NPAM Council, AHA
   
 
Editorial Boards
 
Journal of Clinical Investigation (1987-2002; 2007-present); Associate Editor (2002-2007)
Journal of Biological Chemistry (1988-2000); ATVB (2001-present)

Circulation Research, Associate Editor (2012-present)

 
 
Selected peer-reviewed publications
 
1. Wang X, Collins HL, Ranalletta M, Fuki IV, Billheimer JT, Rothblat GH, Tall AR, Rader DJ (2007).  Macrophage ABCA1 and ABCG1, but not SR-BI, promote macrophage reverse cholesterol transport in vivo.  J Clin Invest. Aug;117(8):2216-24.
PMID: 17657311.

2. Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, Lopez-Sendon J, Mosca L, Tardif JC, Waters DD, Shear CL, Revkin JH, Buhr KA, Fisher MR, Tall AR, Brewer B; ILLUMINATE Investigators (2007).  Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med.Nov 22;357(21):2109-22. Epub Nov 5. PMID: 17984165.

3. Yvan-Charvet L, Ranalletta M, Wang N, Han S, Terasaka N, Li R, Welch C, Tall AR. J Clin Invest (2007).  Combined deficiency of ABCA1 and ABCG1 promotes foam cell accumulation and accelerates atherosclerosis in mice. Dec;117(12):3900-8.
PMID: 17992262.

4. Wang N, Yvan-Charvet L, Lütjohann D, Mulder M, Vanmierlo T, Kim TW, Tall AR (2007) (2008).  ATP-binding cassette transporters G1 and G4 mediate cholesterol and desmosterol efflux to HDL and regulate sterol accumulation in the brain.  FASEB J. Apr;22 (4):1073-82. Epub Nov 26. PMID: 18039927.

5. Tall AR, Yvan-Charvet L, Terasaka N, Pagler T, Wang N (2008).  HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis.  Cell Metab. May; 7 (5):365-75. Review. PMID: 18460328.

6. Yvan-Charvet L, Welch C, Pagler TA, Ranalletta M, Lamkanfi M, Han S, Ishibashi M, Li R, Wang N, Tall AR (2008).  Increased inflammatory gene expression in ABC transporter-deficient macrophages: free cholesterol accumulation, increased signaling via toll-like receptors, and neutrophil infiltration of atherosclerotic lesions.  Circulation. Oct 28; 118(18):1837-47. Epub Oct 13. PMID: 18852364.

7. Terasaka N, Yu S, Yvan-Charvet L, Wang N, Mzhavia N, Langlois R, Pagler T, Li R, Welch CL, Goldberg IJ, Tall AR (2008).  ABCG1 and HDL protect against endothelial dysfunction in mice fed a high-cholesterol diet.  J Clin Invest. Nov;118(11):  3701-13. Epub Oct 16. PMID: 18924609.

8. Westerterp M, Koetsveld J, Yu S, Han S, Li R, Goldberg I. J., Welch C. L., Tall AR.  Increased atherosclerosis in mice with vascular ABCG1 deficiency.  Arterioscler Thromb Vasc Biol. Author manuscript; available in PMC 2011 November 1.Published in final edited form as: Arterioscler Thromb Vasc Biol. 2010 November; 30(11): 2103–2105. Published online 2010 August 12.  PMCID: PMC3116721

9. Yvan-Charvet L, Pagler TA, Seimon TA, Thorp E, Welch CL, Witztum JL, Tabas I, Tall ARABCA1 and ABCG1 Protect Against Oxidative Stress-Induced Macrophage Apoptosis During Efferocytosis.  Circ Res. 2010 Jun 25;106(12):1861-9. Epub 2010 Apr 29.PMID: 20431058

10. Yvan-Charvet L, Pagler T, Gautier EL, Avagyan S, Siry RL, Han S, Welch CL, Wang N, Randolph GJ, Snoeck HW, Tall ARATP-Binding Cassette Transporters and HDL Suppress Hematopoietic Stem Cell Proliferation.  Science. 2010 Science. 2010 Jun 25;328(5986):1689-93. Epub 2010 May 20.PMID: 20488992

11. Pagler TA, Wang M, Mondal M, Murphy AJ, Westerterp M, Moore KJ, Maxfield FR, Tall ARDeletion of ABCA1 and ABCG1 Impairs Macrophage Migration Because of Increased Rac1 Signaling.
Circ Res. Author manuscript; Published in final edited form as: Circ Res. 2011 January 21; 108(2): 194–200. Published online 2010 December 9. PMCID: PMC3097897

12.  Murphy AJ, Akhtari M, Tolani S, Pagler T, Bijl N, Kuo CL, Wang M, Sanson M, Abramowicz S, Welch C, Bochem AE, Kuivenhoven JA, Yvan-Charvet L, Tall AR   ApoE regulates hematopoietic stem cell proliferation, monocytosis, and monocyte accumulation in atherosclerotic lesions in mice. J Clin Invest. 2011 Oct 3;121(10):4138-49. PMID: 21968112  PMCID:  PMC3195472

13.  Ai D, Chen C, Han S, Ganda A, Murphy AJ., Haeusler R, Thorp E, Accili D, Horton J. D., Tall AR. Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice.  J Clin Invest. 2012 April 2; 122(4): 1262–1270. PMCID: PMC3314476

14.  Ai D, Baez JM., Jiang H, Conlon DM., Hernandez-Ono A, Frank-Kamenetsky M, Milstein S, Fitzgerald K, Murphy AJ., Woo CW., Strong A, Ginsberg HN., Tabas I, Rader DJ., Tall AR (2012). Activation of ER stress and mTORC1 suppresses hepatic sortilin-1 levels in obese mice. J Clin Invest. 2012 May 1; 122(5): 1677–1687. PMCID: PMC3336989

15.  Westerterp M*, Gourion-Arsiquaud S*, Murphy AJ*, Shih A, Cremers S, Levine RL, Tall AR†, Yvan-Charvet L†. Regulation of hematopoietic stem and progenitor cell mobilization by cholesterol efflux pathways. Cell Stem Cell 2012, in press.
*,† authors contributed equally.