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The role of HIV Vif in clonal hematopoiesis and malignant transformation (HIV-Associated Cancers in Aging Populations)

Award Number: P30CA125123
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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The role of HIV Vif in clonal hematopoiesis and malignant transformation (HIV-Associated Cancers in Aging Populations) - We accrue somatic mosaicism with age in many tissues. In the blood system, this is called clonal hematopoiesis (CH). CH is a premalignant condition in which hematopoietic stem cells (HSCs) accrue 1-2 mutations among ~20 genes such as DNMT3A, TET2, and ASXL1. The CH clone size and the rate at which clones expand, which are promoted by external factors such as inflammation, are strong predictors of malignant transformation of CH into hematologic malignancies. Consistently, inflammation has been shown to promote the progression of CH to hematologic malignancies. HIV-infected patients exhibit signatures of enhanced inflammation, such as activated immune cells and cytokine expression, even when the patients are treated with antiretroviral therapies (ART). Indeed, people living with HIV (PLWH) have higher incidence of CH, particularly those with ASXL1 mutations, than HIV negative population. Notably, PLWH have a higher risk of developing hematologic malignancies such as non-Hodgkin lymphoma (NHL) and myelodysplastic syndromes (MDS), suggesting an association between the elevated CH prevalence among PLWH and its malignant transformation. The fact that PLWH treated with ART have high incidence of CH raises a possibility that HIV infection promotes CH independently of viral load or inflammation. HIV-infected human hematopoietic stem cells (HSCs) have been found in PLWH, further supporting the possibility that HIV infection may alter HSC function cell intrinsically to confer competitive advantages to mutant HSCs. The objective of this project is to elucidate the molecular mechanisms underpinning the increased prevalence of CH and its transformation to malignancies among PLWH. In Aim 1, we will study whether Asxl1 mutant HSCs expands upon HIV infection. In Aim 2, we will examine whether HIV infection transforms Asxl1 mutant HSCs to myeloid neoplasms. Completion of this study will provide novel insights into the effects of HIV infection on clonal expansion and subsequent transformation of Asxl1 mutant HSCs.


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 = $3,767,288 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	000	18	6/21/2024	NON-COMPETING CONTINUATION	$3,517,288
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	001	18	9/20/2024	SUPPLEMENT FOR EXPANSION	$250,000
														Subtotal = $3,767,288

Issue Date FY: 2023 ( Subtotal = $3,610,888 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	004	17	6/28/2023	NON-COMPETING CONTINUATION	$3,517,288
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	005	17	8/25/2023	SUPPLEMENT FOR EXPANSION	$93,600
2023	2022	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	003	16	6/6/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2022	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	002	16	6/6/2023	NON-COMPETING CONTINUATION	$0
2023	2020	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	001	14	2/28/2023	COMPETING CONTINUATION	$194,100
2023	2019	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	000	13	2/28/2023	NON-COMPETING CONTINUATION	-$194,100
														Subtotal = $3,610,888

Issue Date FY: 2022 ( Subtotal = $3,667,054 )
2022	2022	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Detection and Diagnosis Research	001	14	5/10/2022	SUPPLEMENT FOR EXPANSION	$69,560
2022	2022	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	003	16	9/12/2022	SUPPLEMENT FOR EXPANSION	$149,766
2022	2022	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	002	16	7/29/2022	NON-COMPETING CONTINUATION	$3,517,288
2022	2020	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Cancer Detection and Diagnosis Research	000	14	10/25/2021	SUPPLEMENT FOR EXPANSION	-$69,560
														Subtotal = $3,667,054

Issue Date FY: 2021 ( Subtotal = $4,151,242 )
2021	2021	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	006	15	8/13/2021	SUPPLEMENT FOR EXPANSION	$175,577
2021	2021	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	003	15	6/28/2021	NON-COMPETING CONTINUATION	$3,517,288
2021	2021	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	007	15	9/23/2021	SUPPLEMENT FOR EXPANSION	$149,836
2021	2021	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	005	15	6/30/2021	SUPPLEMENT FOR EXPANSION	$60,000
2021	2021	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	004	15	6/29/2021	SUPPLEMENT FOR EXPANSION	$248,541
2021	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	002	14	1/11/2021	COMPETING CONTINUATION	$850,082
2021	2019	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	001	13	1/11/2021	SUPPLEMENT FOR EXPANSION	-$118,875
2021	2019	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	000	13	1/11/2021	NON-COMPETING CONTINUATION	-$731,207
														Subtotal = $4,151,242

Issue Date FY: 2020 ( Subtotal = $5,098,587 )
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	006	14	9/4/2020	SUPPLEMENT FOR EXPANSION	$150,000
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	005	14	9/3/2020	SUPPLEMENT FOR EXPANSION	$100,000
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	004	14	9/2/2020	COMPETING CONTINUATION	$0
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	000	14	8/14/2020	COMPETING CONTINUATION	$3,517,288
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	009	14	9/9/2020	SUPPLEMENT FOR EXPANSION	$150,000
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Detection and Diagnosis Research	001	14	8/24/2020	SUPPLEMENT FOR EXPANSION	$400,938
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	007	14	9/7/2020	SUPPLEMENT FOR EXPANSION	$0
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	003	14	8/26/2020	SUPPLEMENT FOR EXPANSION	$250,000
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	002	14	8/25/2020	SUPPLEMENT FOR EXPANSION	$60,000
2020	2020	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	008	14	9/8/2020	SUPPLEMENT FOR EXPANSION	$470,361
														Subtotal = $5,098,587

Issue Date FY: 2019 ( Subtotal = $3,321,994 )
2019	2019	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	001	13	8/30/2019	SUPPLEMENT FOR EXPANSION	$118,875
2019	2019	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	000	13	7/22/2019	NON-COMPETING CONTINUATION	$3,203,119
														Subtotal = $3,321,994

Issue Date FY: 2018 ( Subtotal = $4,196,995 )
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	001	12	8/20/2018	SUPPLEMENT FOR EXPANSION	$118,875
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	002	12	8/21/2018	SUPPLEMENT FOR EXPANSION	$249,997
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	000	12	8/8/2018	NON-COMPETING CONTINUATION	$3,203,119
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Minority Health and Health Disparities Research	004	12	9/18/2018	SUPPLEMENT FOR EXPANSION	$500,000
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	003	12	9/11/2018	SUPPLEMENT FOR EXPANSION	$125,004
														Subtotal = $4,196,995

Issue Date FY: 2017 ( Subtotal = $3,862,579 ) (Continued on the next page)
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	003	11	7/28/2017	SUPPLEMENT FOR EXPANSION	$118,875
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	004	11	8/1/2017	SUPPLEMENT FOR EXPANSION	$122,250
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	005	11	9/20/2017	SUPPLEMENT FOR EXPANSION	$250,002
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	001	11	7/10/2017	NON-COMPETING CONTINUATION	$3,253,119
2017	2017	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Cancer Centers Support Grants	002	11	7/17/2017	SUPPLEMENT FOR EXPANSION	$118,333
Grand Total All Awards = $63,056,563

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The role of HIV Vif in clonal hematopoiesis and malignant transformation (HIV-Associated Cancers in Aging Populations)

Award Number: P30CA125123

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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