W. Sean Davidson, Ph.D.
Professor, Department of Pathology and Laboratory Medicine
Genome Research Institute
2120 East Galbraith Road
Cincinnati OH, 45237

Phone: 513-558-3707
Fax: 513-5581312
Sean.Davidson@uc.edu


Email Sean


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• THE DAVIDSON LAB HOMEPAGE

Honors
Funding
Publications

In human beings, the blood levels of high-density lipoprotein (HDL) are inversely correlated with the risk of cardiovascular diseases, the #1 killer in this country. A major cause of cardiovascular disease is the accumulation of cholesterol in blood vessels such as those that supply oxygen to the heart or brain. Fatty plaques accumulate in the artery wall and eventually close off the artery to blood flow - a condition called atherosclerosis. Unfortunately, the detailed mechanisms for HDL’s protective role are not well understood.

The goal of our laboratory is to understand the detailed molecular events by which HDL removes cholesterol from cells. We are particularly interested in the three dimenstional structure of apolipoproteins composing HDL as well as the mode of cholesterol efflux mediated by a transport protein called the ATP binding cassette transporter (ABCA1). We use a wide range of techniques spanning biophysical chemistry, molecular biology and cell biology to understand the structural basis underlying HDL metabolism. The projects in the lab are well suited for graduate or PTSP students because they are highly focused, mechanistic studies on disease-relevant problems that do not have the time constraints of long-term animal studies. Our ultimate objective is to apply what we learn to future drug therapies designed to reduce the high prevalence of cardiovascular disease.


Honors:
2004 Peter Dolphin Award for original and outstanding contributions to HDL research. The International HDL Research Awards Program.

2000/01/03/04 “Teacher of the Year”, Pathobiology Graduate Program, University of Cincinnati.

2003 Richard Akeson Excellence in Graduate Teaching Award. UC College of Medicine

2000 “Established Investigator” National American Heart Association.


Funding Support
HL082734-01A1 (PI: Davidson) 7/1/2006 – 6/30/2010
NIH/NHLBI “The roles of apolipoprotein A-IV structure and lipid affinity in its function”

2 R01 HL 62542-06 (PI: Davidson) \ 4/1/2004 – 3/31/2009
NIH/NHLBI “Mechanisms of apolipoprotein-mediated cholesterol efflux.”

Pfizer International HDL Award (PI: Davidson) 10/1/2005-9/30/2007
Pfizer Pharmaceuticals “The role of ceramide in ABCA1-mediated cholesterol efflux.”

1-U24DK59630-01 (Core A) (PI: Patrick Tso) 8/01/06-7/31/11
NIH/NIDDK “The University of Cincinnati Mouse Diabetes Phenotyping Center.”

1 RO1 HL67093-03 (PI: Davidson) 8/1/2002 – 7/31/2006 (no cost ext.)
NIH/NHLBI “The structure of apolipoprotein A-I in high density lipoprotein.”


Publications

1:	Davidson WS, Ghering AB, Beish L, Tubb MR, Hui DY, Pearson K The biotin-capture lipid affinity assay: a rapid method for determining lipid binding parameters for apolipoproteins. J Lipid Res. 2006 Feb;47(2):440-9. PMID: 16267343 [PubMed - indexed for MEDLINE]

2:	Pearson K, Tubb MR, Tanaka M, Zhang XQ, Tso P, Weinberg RB, Davidson WS Specific sequences in the N and C termini of apolipoprotein A-IV modulate its conformation and lipid association. J Biol Chem. 2005 Nov;280(46):38576-82. PMID: 16159879 [PubMed - indexed for MEDLINE]

3:	Silva RA, Hilliard GM, Li L, Segrest JP, Davidson WS A mass spectrometric determination of the conformation of dimeric apolipoprotein A-I in discoidal high density lipoproteins. Biochemistry. 2005 Jun;44(24):8600-7. PMID: 15952766 [PubMed - indexed for MEDLINE]

4:	Davidson WS, Silva RA Apolipoprotein structural organization in high density lipoproteins: belts, bundles, hinges and hairpins. Curr Opin Lipidol. 2005 Jun;16(3):295-300. PMID: 15891390 [PubMed - indexed for MEDLINE]

5:	Pearson K, Liu M, Shen L, Tso P, Davidson WS Bacterial expression and characterization of rat apolipoprotein E. Protein Expr Purif. 2005 Jun;41(2):447-53. PMID: 15866734 [PubMed - indexed for MEDLINE]

6:	Silva RA, Hilliard GM, Fang J, Macha S, Davidson WS A three-dimensional molecular model of lipid-free apolipoprotein A-I determined by cross-linking/mass spectrometry and sequence threading. Biochemistry. 2005 Mar;44(8):2759-69. PMID: 15723520 [PubMed - indexed for MEDLINE]

7:	Maiorano JN, Jandacek RJ, Horace EM, Davidson WS Identification and structural ramifications of a hinge domain in apolipoprotein A-I discoidal high-density lipoproteins of different size. Biochemistry. 2004 Sep;43(37):11717-26. PMID: 15362856 [PubMed - indexed for MEDLINE]

8:

Pearson K, Saito H, Woods SC, Lund-Katz S, Tso P, Phillips MC, Davidson WS Structure of human apolipoprotein A-IV: a distinct domain architecture among exchangeable apolipoproteins with potential functional implications. Biochemistry. 2004 Aug;43(33):10719-29. PMID: 15311933 [PubMed - indexed for MEDLINE]

9:	Davidson WS 5th Annual International Conference on HDL Cholesterol: metabolic pathways and drug developments. Expert Opin Ther Targets. 2004 Aug;8(4):359-66. PMID: 15268630 [PubMed - indexed for MEDLINE]

10:	Narayanaswami V, Maiorano JN, Dhanasekaran P, Ryan RO, Phillips MC, Lund-Katz S, Davidson WS Helix orientation of the functional domains in apolipoprotein e in discoidal high density lipoprotein particles. J Biol Chem. 2004 Apr;279(14):14273-9. PMID: 14739281 [PubMed - indexed for MEDLINE]