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Exosome-mediated soluble insulin receptor secretion correlates with HAND Administrative Supplement Hurricanes

Award Number: R01NS099036
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/16/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2020

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Exosome-mediated soluble insulin receptor secretion correlates with HAND Administrative Supplement Hurricanes - The prevalence of HIV-associated neurocognitive disorders (HAND) has increased owing to the widespread use of combined antiretroviral treatment (cART) and resulting longer survival of HIV-infected patients. Among HIV-seropositive patients on cART, most suffer from the milder forms of HAND. Recently, blood sugar metabolism abnormalities have been identified in HIV-infected individuals and associated with HAND. Retrospective data from our cohort showed that exosomes from HIV-seropositive women on cART contain high levels of sIR as well as HIV-1 Tat, and that exosomal levels of both sIR and HIV-1 Tat are associated with the presence and severity of HAND in these women. Our long-term goal is to identify novel mechanisms to explain the pathogenic process of insulin resistance and cognitive impairment in HIV-seropositive population. The rationale for the current study lies with previous observations by our lab and others that blood sugar metabolism abnormalities are associated with HAND. Our central hypothesis is that elevated levels of plasma exosomal sIR and PBMCs SF2-ASF/hnRNPA1 ratio contribute to high levels of plasma sIR and the development and progression of HAND. The objective of this study is to examine the relationship of sIR plasma levels, exosomal sIR levels, SF2-ASF/hnRNPA1 ratio levels, insulin resistance, and HAND in a cohort of HIV-seropositive patients on cART. We propose the following AIMs: 1. To determine if sIR and HIV-1 Tat levels in plasma exosomes are associated with HAND, 2. To determine if the SF2-ASF/hnRNPA1 splicing factors ratio is associated with HAND and correlates with the levels of exosomal sIR, and 3. To determine the influence of gender differences in the levels of plasma exosomal sIR and HIV-1 Tat and PBMCs SF2- ASF/hnRNPA1 ratio of HIV-seropositive participants with HAND. We expect an association between plasma sIR levels, exosomal sIR and HIV-1 Tat, SF2-ASF/hnRNPA1 ratio levels, insulin resistance, and HAND in a cohort of HIV-seropositive women using cART. This is a novel study for the detection of exosomal sIR and HIV-1 Tat and the identification of the mechanisms responsible for the secretion of sIR-full length to the plasma of HIV-seropositive patients. It is significant since the identification of these molecular mechanisms in the neuropathophysiology of HAND could serve to design novel approaches and treatment regimens for the prevention and treatment of insulin resistance and cognitive impairment in HIV-seropositive patients.


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: 2026 ( Subtotal = -$85,294 )
2026	2019	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	B622 MAIN BUILDING FLR 6	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Restoration Program: Hurricanes Harvey, Maria, and Irma – non-construction	000	4	10/1/2025	SUPPLEMENT FOR EXPANSION	-$85,294
														Subtotal = -$85,294

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	B622 MAIN BUILDING FLR 6	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	4/4/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	B622 MAIN BUILDING FLR 6	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	3/30/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $485,146 )
2021	2021	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	3/9/2021	NON-COMPETING CONTINUATION	$485,146
2021	2019	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Restoration Program: Hurricanes Harvey, Maria, and Irma – non-construction	000	4	3/8/2021	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $485,146

Issue Date FY: 2019 ( Subtotal = $873,452 )
2019	2019	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Restoration Program: Hurricanes Harvey, Maria, and Irma – non-construction	002	4	4/16/2019	SUPPLEMENT FOR EXPANSION	$388,306
2019	2019	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	4/15/2019	NON-COMPETING CONTINUATION	$0
2019	2019	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/21/2019	NON-COMPETING CONTINUATION	$485,146
														Subtotal = $873,452

Issue Date FY: 2018 ( Subtotal = $452,866 )
2018	2018	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	9/19/2018	SUPPLEMENT FOR EXPANSION	$64,560
2018	2018	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	5/8/2018	NON-COMPETING CONTINUATION	$38,831
2018	2018	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/27/2018	NON-COMPETING CONTINUATION	$349,475
														Subtotal = $452,866

Issue Date FY: 2017 ( Subtotal = $388,306 )
2017	2017	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	6/2/2017	NON-COMPETING CONTINUATION	$38,831
2017	2017	UNIVERSITY OF PUERTO RICO MEDICAL SCIENCES CAMPUS	MAIN BLDG FLR 6 B-622	SAN JUAN	PR	00935	SAN JUAN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/28/2017	NON-COMPETING CONTINUATION	$349,475
														Subtotal = $388,306

Issue Date FY: 2016 ( Subtotal = $388,306 )
2016	2016	UNIVERSITY OF PUERTO RICO - MEDICAL SCIENCE CAMPUS	POST OFFICE BOX 365067	SAN JUAN	PR			USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/9/2016	NEW	$388,306
														Subtotal = $388,306

Grand Total All Awards = $2,502,782

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Exosome-mediated soluble insulin receptor secretion correlates with HAND Administrative Supplement Hurricanes

Award Number: R01NS099036

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/16/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2020

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