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Microsystems to Decipher Leukocyte Decision-Making

Award Number: R35GM133610
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: 09/01/2019
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Microsystems to Decipher Leukocyte Decision-Making - Emerging studies suggest that innate immune cells, such neutrophils, can adopt multiple activation/differentiation states, either conducive or detrimental to host defense and inflammation resolution. The conceptual existence of diverse activation states of innate leukocytes is also evident in circulating leukocytes from healthy individuals and patients with system inflammatory syndromes such as sepsis. However, quantification and understanding of single-cell phenotypes in a spectrum of differentiation states is lacking. This bottle-neck explains the complete lack of cure for sepsis, despite decades of extensive basic and translational studies. The overarching focus of the research program in my laboratory is to define and quantify principal factors that underlie the decision-making processes of immune cell migration, differentiation and activation in response to challenges. The research funded by this award will combine technologies, experimental methods, and modeling approaches to investigate leukocyte decision-making in the context of activation state and sepsis. In the past 5 years, we have engineered microfluidic platforms to quantify neutrophil migratory and anti-microbial decision-making. Building off of our current work with neutrophils and microfluidic platforms, over the next five years we propose to: 1) Develop, improve and implement state-of-the-art multi-sensing platforms to analyze septic patient leukocyte migratory and antimicrobial phenotypes in precisely defined microenvironments. Mathematical models will be created based on known molecular pathways and will be validated by the molecular signatures from septic patients and healthy donors; 2) Quantify leukocyte migratory and anti-microbial functions in vivo using novel implantable hydrogels combined with intra-vital imaging techniques in a mouse sepsis model. By defining the fundamental processes, including differentiation state and microenvironment, that determine a leukocyte’s phenotype, we can better predict, diagnose, and eventually design effective treatments for sepsis. These fundamental processes involve general biology principles at cellular and molecular levels applicable to diverse eukaryotic cells, lending broader significance to our proposed investigation. The work proposed is highly innovative because it integrates methods from different scientific disciplines to solve the “big problem” of sepsis. Novel microfluidic platforms will be engineered to measure single-cell phenotypes in precisely defined conditions and directly connect these phenotypes to the molecular signature of the cell. Our vision is to integrate these quantitative single cell measurements with computational modeling and analysis to create intuitive descriptions of complex leukocyte decision-making processes. Finally, these devices have clear translational potential and may be used in the future in a hospital setting to assist with diagnosing or monitoring treatment of sepsis.


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	2023	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Biomedical Research and Research Training	000	6	1/29/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $386,568 )
2023	2023	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Biomedical Research and Research Training	000	6	6/26/2023	NON-COMPETING CONTINUATION	$386,568
														Subtotal = $386,568

Issue Date FY: 2022 ( Subtotal = $375,882 )
2022	2022	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Biomedical Research and Research Training	000	5	6/29/2022	NON-COMPETING CONTINUATION	$375,882
														Subtotal = $375,882

Issue Date FY: 2021 ( Subtotal = $356,565 )
2021	2021	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Biomedical Research and Research Training	002	4	6/21/2021	NON-COMPETING CONTINUATION	$364,437
2021	2021	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Biomedical Research and Research Training	005	4	7/19/2021	NON-COMPETING CONTINUATION	$0
2021	2020	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Biomedical Research and Research Training	001	3	2/19/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$348,887
2021	2020	VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY	300 TURNER ST NW STE 4200	BLACKSBURG	VA	24061	MONTGOMERY	USA	Biomedical Research and Research Training	000	2	2/19/2021	NON-COMPETING CONTINUATION	-$356,759
2021	2020	UNIVERSITY OF TEXAS AT DALLAS	800 W CAMPBELL RD	RICHARDSON	TX	75080	DALLAS	USA	Biomedical Research and Research Training	004	3	7/11/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$122,150
2021	2019	VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY	300 TURNER ST NW STE 4200	BLACKSBURG	VA	24061	MONTGOMERY	USA	Biomedical Research and Research Training	003	1	7/11/2021	NEW	-$122,150
														Subtotal = $356,565

Issue Date FY: 2020 ( Subtotal = $356,759 )
2020	2020	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW STE 4200	BLACKSBURG	VA	24061	MONTGOMERY	USA	Biomedical Research and Research Training	000	2	6/11/2020	NON-COMPETING CONTINUATION	$356,759
														Subtotal = $356,759

Issue Date FY: 2019 ( Subtotal = $359,514 )
2019	2019	VIRGINIA POLYTECHNIC INSTITUTE & STATE UNIVERSITY	300 TURNER ST NW STE 4200	BLACKSBURG	VA	24061	MONTGOMERY	USA	Biomedical Research and Research Training	000	1	8/12/2019	NEW	$359,514
														Subtotal = $359,514

Grand Total All Awards = $1,835,288

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Microsystems to Decipher Leukocyte Decision-Making

Award Number: R35GM133610

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: 09/01/2019

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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