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New tools for tracking single cells in vivo

Award Number: R01EB030367
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2020
PERIOD OF PERFORMANCE END DATE: 10/31/2025

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New tools for tracking single cells in vivo - Abstract This project will develop a new pipeline for tracking the migration of single cells in vivo at the whole-body level. Cell migration is a crucial biological process involved in the pathology and treatment of some of the world’s most intractable diseases. Stem cell therapy and immunotherapy, for instance, are emerging as viable treatments for conditions previously thought incurable, such as heart failure and diabetes. Unfortunately, cell tracking methods remain inadequate to fully capitalize on these recent advances. Currently, cell tracking relies on imaging the distribution of a specific population of cell through a contrast agent, which is either directly affixed to the cells or targeted towards an engineered reporter protein. This approach precludes precise measurement of cell circulation kinetics or migration routes. Furthermore, due to efflux and non-specific retention, the distribution of the contrast agent does not necessarily match the underlying distribution of cells. In view of these challenges, we consider a novel approach that has the potential to revolutionize cell tracking. While current methods aim to track bulk populations of cells, we hypothesize that novel biological insight may be gained by tracking cells individually, in small numbers, with unprecedented temporal and spatial accuracy. We will pursue the development of CellGPS, a method capable of tracking the 3D position of individual cells continuously as these cells migrate through the body of a living subject. To accomplish this goal, we rely on a previously developed algorithm that can extract the position of a moving cell directly from the raw list-mode output of a positron emission tomography (PET) scanner. PET is the most sensitive imaging modality available for whole-body human imaging and, therefore, the ideal imaging modality for this project. Building on extensive preliminary studies, we plan to pursue the following four specific aims: (1) develop a rapid, safe and robust strategy for radiolabeling cells; (2) design and build a novel microfluidics pipeline to molecularly profile and isolate single cells for in vivo tracking; (3) evaluate single-cell tracking as a readout of cell dissemination in an experimental model of metastatic melanoma; and (4) explore translation of this technology to human imaging scanners. This project is expected to generate a positive impact for biomedical research both in the pre-clinical and clinical setting. For instance, single-cell tracking could be used to determine the spatiotemporal kinetics of cell migration during the earliest phase of the metastatic cascade. The method could also help determine the dynamic distribution of cells after transplantation for cell-based therapy, which could help predict response and optimize treatment regimen. This project will achieve critical milestones towards routine and reproducible tracking of single cells in vivo using PET.


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 = $589,925 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	4	6/26/2024	NON-COMPETING CONTINUATION	$48,157
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	4	12/5/2023	NON-COMPETING CONTINUATION	$541,768
														Subtotal = $589,925

Issue Date FY: 2023 ( Subtotal = $588,962 )
2023	2023	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	3	11/4/2022	NON-COMPETING CONTINUATION	$530,066
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	002	3	2/3/2023	NON-COMPETING CONTINUATION	$58,896
2023	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	11/3/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $588,962

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	5/20/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $620,088 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	2	5/26/2021	NON-COMPETING CONTINUATION	$0
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	4/30/2021	NON-COMPETING CONTINUATION	$620,088
														Subtotal = $620,088

Issue Date FY: 2020 ( Subtotal = $650,016 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	001	1	9/9/2020	NEW	$0
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	8/27/2020	NEW	$650,016
														Subtotal = $650,016

Grand Total All Awards = $2,448,991

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New tools for tracking single cells in vivo

Award Number: R01EB030367

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2020

PERIOD OF PERFORMANCE END DATE: 10/31/2025

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