Monday, January 19, 2026 1/19/2026

Function and Regulation of MEIS1 in Vascular Disease

Award Number: K99HL169827
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/01/2023
PERIOD OF PERFORMANCE END DATE: 07/14/2025

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Function and Regulation of MEIS1 in Vascular Disease - PROJECT SUMMARY Vascular smooth muscle cells (VSMCs), the major cell type of medium- and large-sized arteries, undergo phenotypic switching in vascular diseases such as post-angioplasty restenosis and atherosclerosis. Understanding the key players that promote VSMC plasticity will inform targeting strategies for downstream signaling pathways and nuclear events effecting pathological changes in gene expression. Myocardin (MYOCD) is a potent transcriptional coactivator of the VSMC differentiated state and loss of expression portends vascular pathology. Despite the hundreds of papers describing MYOCD expression and activity in various contexts, its transcriptional regulation in vivo is virtually unknown. I have discovered a binding site for Myeloid Ecotropic Viral Integration Site 1 (MEIS1), a previously unrecognized transcription factor in VSMCs, in the 5’ promoter region of Myocd, and preliminary studies show MEIS1 binding and transactivation of the Myocd gene. MEIS1 is reduced in human VSMCs of atherosclerotic coronary arteries and transcriptomic profiling from Biobank of Karolinska Endoarterctomy (BiKE) showed significant down-regulation of MEIS1 in plaques versus normal arteries as well as in symptomatic versus asymptomatic patients. To date, there has been only one report of MEIS1 in VSMCs and nothing known beyond descriptive findings in pulmonary hypertension. Previous Meis1 loss-of-function and protein expression studies have been difficult to interpret because of the lack of a true null mouse model and faulty commercial antibodies. Preliminary studies below show an increased proliferation and migration of VSMCs with loss of Meis1 function; gain-of-function studies reveal the maintenance of the contractile state. I have generated a versatile mouse model representing the first true null Meis1 allele and its detection at the protein level. An important component of my studies will be the utilization of a new VSMC-restricted Cre driver I have helped characterize (Itga8-CRERT2) for more refined in vivo loss-of-function studies. Additional studies support multiple enhancers that drive VSMC expression of Meis1. Collectively, the preliminary work support my hypothesis that MEIS1 is a VSMC enriched transcription factor that promotes VSMC differentiation via transactivation of Myocd. I propose to test this hypothesis in three aims over the course of this K99/R00 award. The K99 Aim 1 will elucidate the VSMC phenotype with loss of endogenous MEIS1. R00 Aim 2 will elucidate the transcriptional regulation of Myocd in vivo through an evolutionarily-conserved MEIS1-response element using state-of-the-art genome editing in mice. R00 Aim 3 will elucidate the functional cis-regulome of MEIS1 in vascular disease. Completion of the proposed studies will provide new insight into the contribution of MEIS1 to VSMC differentiation and vascular homeostasis and the mechanistic regulation of Meis1 in vascular diseases. Conceptual and experimental training related to multi-omics related research during the K99 phase will help me pursue advanced MEIS1 studies as an independent investigator during my R00 phase and position me well for my first R01 application.


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 = $0 )
2026	2024	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	000	2	1/15/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	000	2	7/10/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $113,520 )
2024	2024	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	000	2	6/28/2024	NON-COMPETING CONTINUATION	$113,520
														Subtotal = $113,520

Issue Date FY: 2023 ( Subtotal = $113,520 )
2023	2023	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	000	1	7/26/2023	NEW	$113,520
														Subtotal = $113,520

Grand Total All Awards = $227,040

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Function and Regulation of MEIS1 in Vascular Disease

Award Number: K99HL169827

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/01/2023

PERIOD OF PERFORMANCE END DATE: 07/14/2025

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