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Effect of methodological and biological variability on molecular profiling of extracellular vesicles in cancer detection

Award Number: R01CA218500
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary A novel paradigm in paracrine signaling has recently emerged based on the findings identifying extracellular vesicles (EVs) as intercellular conveyors of biological information both in normal and pathological conditions such as cancer. EVs and their cargo have been shown by us and others to regulate gene expression and alter cell function in various cell types. Moreover, during pathological conditions such as cancer, the number and compositions of EVs alter the host immune response as well as synchronize the behavior of secondary tumors. Isolation and molecular profiling of EVs (i.e. RNAs, proteins, post-translational modifications, lipids, metabolites) both in health and disease are critical for understanding EVs' biogenesis and effector functions. Currently, the study of EVs as biological entities relevant for intracellular signaling and disease diagnosis is based on the assumption that the biogenesis and removal of EVs happen at a steady state rate, being modified mostly by the healthy/diseased status of the host. Our published results show that that is not the case. Our data indicate that the tissue-origin, number, size distribution, as well as protein, lipid, metabolite and RNA composition of EVs isolated by standard techniques depend not just on the blood collection methods, but also on the time of the day the blood samples were collected. Therefore, systematic assessment of these factors and other sources of variability in EV profiles are important for enabling basic biology, clinical and personalized medicine applications. Although it is beyond the purpose of this grant, the long-term goal of our team is to establish reproducible methods for blood collection and sample processing that would allow us to identify the specific molecular EV signatures during the day/night cycle, with the aim of pinpointing the ideal, organ-specific times for blood collection, which would increase the reliability and specificity of early cancer detection. We believe that establishing biological and methodological baselines are absolutely vital for correctly comparing proteomics and glycomics data obtained in various studies, as well as interpreting the data obtained from patients' samples.


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: 2022 ( Subtotal = $1,080,874 )
2022	2022	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	5	2/24/2022	NON-COMPETING CONTINUATION	$611,815
2022	2022	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	002	5	9/9/2022	SUPPLEMENT FOR EXPANSION	$414,671
2022	2022	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	5	5/23/2022	NON-COMPETING CONTINUATION	$54,388
														Subtotal = $1,080,874

Issue Date FY: 2021 ( Subtotal = $680,042 )
2021	2021	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	4	3/17/2021	NON-COMPETING CONTINUATION	$680,042
														Subtotal = $680,042

Issue Date FY: 2020 ( Subtotal = $680,809 )
2020	2020	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	3	2/27/2020	NON-COMPETING CONTINUATION	$680,809
2020	2019	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	2	11/20/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $680,809

Issue Date FY: 2019 ( Subtotal = $851,560 )
2019	2019	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	001	2	9/6/2019	NON-COMPETING CONTINUATION	$188,122
2019	2019	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	2	2/12/2019	NON-COMPETING CONTINUATION	$663,438
														Subtotal = $851,560

Issue Date FY: 2018 ( Subtotal = $677,886 )
2018	2018	NORTHEASTERN UNIVERSITY	360 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Cancer Detection and Diagnosis Research	000	1	3/15/2018	NEW	$677,886
														Subtotal = $677,886

Grand Total All Awards = $3,971,171

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Effect of methodological and biological variability on molecular profiling of extracellular vesicles in cancer detection

Award Number: R01CA218500

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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