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Transendothelial transport mediated modulations to the High Density Lipoprotein

Award Number: SC3GM105561
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2013
PERIOD OF PERFORMANCE END DATE: 08/31/2023

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Transendothelial transport mediated modulations to the High Density Lipoprotein - Title: Transendothelial transport mediated modulations to the High Density Lipoprotein Summary Despite the vast amount of literature that indicates low plasma levels of HDL-cholesterol (HDL-C) is a risk factor for cardiovascular disease (CVD), the last decade has seen a paradigm shift in the concept that it may not be HDL-C levels per se but the functionality of HDL that is a determining factor in CVD. The shift in focus is in light of several studies that show that neither pharmacological nor genetic intervention to increase HDL-C levels, lower the risk for CVD. Thus, there is a pressing need to fill the gap in knowledge regarding the role of HDL in CVD from a mechanistic perspective and understand structure-function relationships in HDL. In the current proposal, we hypothesize that apolipoprotein (apo) AI and apoE3, two critical apos on HDL, undergo structural alterations and post translational modifications (PTM) and that HDL undergoes particle modulation as a consequence of transendothelial transport from plasma to the arterial intima with significant functional penalties. We will test this hypothesis by interrogating structure-function changes to the HDL with two specific aims: (1) Identify structural and proteomic alterations to the HDL associated with transendothelial transport across aortic endothelial cells, and, (2) Determine changes in HDL function following transendothelial transport. We will carry out spectroscopic analysis of reconstituted HDL (rHDL) bearing spatially sensitive fluorescent probes at flexible locations on apoAI or apoE3 to obtain insight into conformational alterations following transcytosis. Based on previous findings about oxidatively modified apoAI in atherosclerotic plaques, we postulate that the apos are susceptible to oxidative modification during transcytosis. To address this, we will determine PTM in transcytosed HDL, specifically on apoAI, apoE3 and selected proteins involved in lipoprotein metabolism by mass spectrometry. We will also perform lipoproteomic analysis to identify changes to the protein and lipid composition of transcytosed HDL. In an independent but complementary approach, we will examine changes in two major functional effects of transcytosed HDL: its ability to promote cholesterol efflux from macrophages, and, its antioxidant activity. Completion of these studies will significantly advance our understanding of the relationship between structure/composition and the atheroprotective effect of HDL at the vascular wall. The expected outcome of the proposed studies is to have a deeper understanding of modulations in HDL that render it dysfunctional. Establishing this relationship will aid in development of HDL- based therapies and identification of biomarkers of CVD risk. The research enhancement objectives of the PI are to: (i) develop expertise in HDL and endothelial cell biology, (ii) increase competitiveness to apply for major external funding by publishing research findings, (iii) strengthen existing and develop new collaborations, submit joint publications and lay the groundwork for developing proposals, and, (iv) establish mentoring, networking, and leadership skills, and offer research training opportunities and mentorship for students from diverse backgrounds in biomedical research.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	CALIFORNIA STATE UNIVERSITY LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	8	5/15/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $110,625 )
2021	2021	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	8	8/16/2021	NON-COMPETING CONTINUATION	$110,625
														Subtotal = $110,625

Issue Date FY: 2020 ( Subtotal = $110,625 )
2020	2020	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	7	8/21/2020	NON-COMPETING CONTINUATION	$110,625
														Subtotal = $110,625

Issue Date FY: 2019 ( Subtotal = $110,625 )
2019	2019	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	001	6	8/13/2019	NON-COMPETING CONTINUATION	$110,625
2019	2016	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	2/17/2019	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $110,625

Issue Date FY: 2018 ( Subtotal = $110,625 )
2018	2018	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	5	9/13/2018	COMPETING CONTINUATION	$110,625
														Subtotal = $110,625

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	001	4	1/23/2017	EXTENSION WITH OR WITHOUT FUNDS	$22,941
2017	2015	CALIFORNIA STATE UNIVERSITY, LONG BEACH RESEARCH FOUNDATION	6300 E STATE UNIVERSITY DR STE 332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	1/23/2017	NON-COMPETING CONTINUATION	-$22,941
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $108,375 )
2016	2016	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	4	5/26/2016	EXTENSION WITH OR WITHOUT FUNDS	$108,375
														Subtotal = $108,375

Issue Date FY: 2015 ( Subtotal = $108,375 )
2015	2015	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	3	5/15/2015	NON-COMPETING CONTINUATION	$108,375
														Subtotal = $108,375

Issue Date FY: 2014 ( Subtotal = $108,375 )
2014	2014	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	2	5/29/2014	NON-COMPETING CONTINUATION	$108,375
														Subtotal = $108,375

Issue Date FY: 2013 ( Subtotal = $108,375 )
2013	2013	CALIFORNIA STATE UNIVERSITY, LONG BEACH FND	6300 STATE UNIVERSITY DR #332	LONG BEACH	CA	90815	LOS ANGELES	USA	Biomedical Research and Research Training	000	1	5/28/2013	NEW	$108,375
														Subtotal = $108,375

Grand Total All Awards = $876,000

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Transendothelial transport mediated modulations to the High Density Lipoprotein

Award Number: SC3GM105561

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2013

PERIOD OF PERFORMANCE END DATE: 08/31/2023

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