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Regulation and modeling of transport across tissue barriers

Award Number: R35GM142835
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: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Regulation and modeling of transport across tissue barriers - Project Summary Physiological transport of fluid, molecules, proteins, and cells throughout the body is critical for homeostasis. While transport processes like cell migration and molecular passage across cellular barriers are well documented, less is known about transport across the interstitial tissue spaces and into lymphatic vessels. Lymphatic vessels are critical for maintenance of tissue homeostasis and forming the adaptive immune response, as they are the natural conduit between peripheral tissues and the lymph nodes (LNs), where the immune response is shaped. Because particulates are primarily shuttled via lymphatic vessels, lymphatics have received considerable attention in recent years as potential targets for drug delivery, particularly for immune modulation. Transport across interstitial tissue governs what enters lymphatic vessels vs. blood vessels and thus understanding extracellular tissues is vital to design therapeutics. However, we do not yet fully understand how physiological processes and conditions such as interstitial flow or inflammation affect transport across interstitial tissue spaces and into lymphatics. My research program will answer two key questions: 1) How do physiological processes affect 1) lymphatic transport and its regulation, and 2) transport across extracellular tissue? To address the first question, we propose to develop physiologically relevant in vitro model systems that can recapitulate conditions within peripheral tissues and nanoparticle tools that both allow probing how specific mechanisms, including fluid flow and inflammation, modulate lymphatic transport specifically. Results from these studies will provide new insights into regulation of lymphatic transport, new model systems for studying lymphatic transport, and new design criteria to maximize targeting lymphatic transport for therapeutic purposes. To address the second question, we will combine two techniques: multiple particle tracking (MPT) and live ex vivo tissue slice cultures. MPT uses nanoparticle diffusion over time to extract information about tissue mesh spacing or microrheology and provides a medium for studying physiological processes like flow. Live tissue slice cultures maintain tissue structure ex vivo and allow for real-time assessment of interstitial tissue structures. Results from combining these techniques will provide a better understanding of how physiological processes affect extracellular spaces and provide insights into design criteria for therapeutics to cross extracellular tissue barriers. In summary, the proposed work will advance our knowledge about physiological processes governing lymphatic transport and its regulation, and also shed light into how processes like inflammation, interstitial flow, and edema affect extracellular tissue spaces. Ultimately, the vision for my lab’s research is to design crucial scientific methods to be used by the broader community, identify design criteria and computational models to predict transport across biological barriers, and design therapeutics and their delivery vehicles for treating diseases by harnessing lymphatic vessel physiology.


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 = $365,998 )
2025	2025	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	5	6/4/2025	NON-COMPETING CONTINUATION	$365,998
														Subtotal = $365,998

Issue Date FY: 2024 ( Subtotal = $381,563 )
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	001	4	6/4/2024	SUPPLEMENT FOR EXPANSION	$21,565
2024	2024	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BUILDING	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	4	6/3/2024	NON-COMPETING CONTINUATION	$359,998
														Subtotal = $381,563

Issue Date FY: 2023 ( Subtotal = $487,320 )
2023	2023	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	001	3	5/25/2023	SUPPLEMENT FOR EXPANSION	$86,259
2023	2023	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	002	3	6/27/2023	SUPPLEMENT FOR EXPANSION	$35,063
2023	2023	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	3	5/24/2023	NON-COMPETING CONTINUATION	$365,998
														Subtotal = $487,320

Issue Date FY: 2022 ( Subtotal = $430,692 )
2022	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	001	2	8/26/2022	SUPPLEMENT FOR EXPANSION	$64,694
2022	2022	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	2	5/6/2022	NON-COMPETING CONTINUATION	$365,998
														Subtotal = $430,692

Issue Date FY: 2021 ( Subtotal = $365,998 )
2021	2021	UNIVERSITY OF MARYLAND, COLLEGE PARK	3112 LEE BLDG 7809 REGENTS DR	COLLEGE PARK	MD	20742	PRINCE GEORGES	USA	Biomedical Research and Research Training	000	1	6/17/2021	NEW	$365,998
														Subtotal = $365,998

Grand Total All Awards = $2,031,571

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Regulation and modeling of transport across tissue barriers

Award Number: R35GM142835

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: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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