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Comparative Retroviral Epigenomics

Award Number: K01OD026565
ORGANIZATION: OFFICE OF THE DIRECTOR, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 09/15/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2024

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Comparative Retroviral Epigenomics - Abstract Despite the successful development of antiretroviral therapies (ART), the long-awaited cure for HIV has still not been discovered. The virus integrates into DNA of tissues throughout the body and becomes latent after institution of ART. Persons receiving ART cannot discontinue their medications, as in most cases the virus will simply rebound upon ART cessation. One approach to finding a cure is to eliminate the reservoir by bringing the virus out of latency so that infected cells might be killed by ART or the host immune system. Epigenetic mechanisms are believed to play an important role in retroviral latency, yet little is known about the epigenetic markers associated with the latent reservoir for HIV. Surprisingly, even less has been published for SIV, where access to tissues and time lines of infection are better characterized and controlled. While SIV-infected macaques serve as a model for human HIV infection, there is no knowledge of whether SIV and HIV epigenetics have any similarity. To develop successful therapeutics that target epigenetic mechanisms of HIV latency, we must first identify these mechanisms and whether animal models will be suitable to test them. The proposed project will characterize the proportion of proviruses located in open chromatin and containing repressive epigenetic marks both during ART and after discontinuation of ART in HIV-infected humans and SIV-infected macaques. Further, I will use these parameters to evaluate the association with the size of the reservoir, cell-associated RNA, and viral rebound after ART cessation in both peripheral T cells and brain, which is a poorly characterized reservoir tissue. These studies will allow me to conclude what role repressive epigenetic marks play in proviral latency, and whether these mechanisms differ between tissues, and species. Importantly, this project will support my development as an independent researcher with expertise in clinical retroviral epigenetics and comparative research. The proposed training will provide me with exposure to trial design and analysis methods, including biostatistics and bioinformatics. These methods are critical to my career development, as we are now heavily reliant on next-generation sequencing technologies, and the comparative studies I wish to pursue will require an understanding of statistical methods for study design and data analysis. Finally, this project will build upon my background in comparative medicine, retrovirology, and epigenetics. I will receive training in 1) clinical epigenetics techniques 2) biostatistics and bioinformatics 3) non- human primate (NHP) procedures and NHP animal welfare 4) ethical conduct of HIV research and 5) professional development, including grantsmanship, building collaborations, and reporting research findings. My mentoring team includes an excellent track records in all proposed areas of training, including retrovirology, epigenetics, biostatistics, bioinformatics, and non-human primate SIV research. This proposal builds upon previous NIH funded research and complements current NIH funded projects.


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: 2025 ( Subtotal = $0 )
2025	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Infrastructure Programs	000	5	11/20/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Infrastructure Programs	000	5	11/3/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $122,640 )
2023	2023	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DRIVE	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Infrastructure Programs	000	5	7/18/2023	SUPPLEMENT FOR EXPANSION	$122,640
														Subtotal = $122,640

Issue Date FY: 2022 ( Subtotal = $122,640 )
2022	2022	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Infrastructure Programs	000	5	6/15/2022	NON-COMPETING CONTINUATION	$122,640
														Subtotal = $122,640

Issue Date FY: 2021 ( Subtotal = $122,640 )
2021	2021	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Infrastructure Programs	000	4	6/15/2021	NON-COMPETING CONTINUATION	$122,640
														Subtotal = $122,640

Issue Date FY: 2020 ( Subtotal = $183,960 )
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Infrastructure Programs	000	2	5/1/2020	SUPPLEMENT FOR EXPANSION	$61,320
2020	2020	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Infrastructure Programs	001	3	6/20/2020	NON-COMPETING CONTINUATION	$122,640
														Subtotal = $183,960

Issue Date FY: 2019 ( Subtotal = $122,640 )
2019	2019	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Infrastructure Programs	000	2	6/22/2019	NON-COMPETING CONTINUATION	$122,640
														Subtotal = $122,640

Issue Date FY: 2018 ( Subtotal = $122,640 )
2018	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Infrastructure Programs	000	1	9/11/2018	NEW	$122,640
2018	2018	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR DEPT 621	LA JOLLA	CA	92093	SAN DIEGO	USA	Research Infrastructure Programs	001	1	9/14/2018	NEW	$0
														Subtotal = $122,640

Grand Total All Awards = $797,160

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Comparative Retroviral Epigenomics

Award Number: K01OD026565

ORGANIZATION: OFFICE OF THE DIRECTOR, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 09/15/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2024

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