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High Dimensional Mass Cytometry Analysis of the Effects of Vedolizumab in Intestinal Cellular Subsets and its Correlation with Clinical Parameters

Award Number: R21DK118927
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary Our understanding of the specific cell subsets that are being depleted by vedolizumab and other effective agents within the intestine remains superficial. This is in part due to technical limitations which had hampered the unbiased interrogation of cellular and molecular composition of the human intestinal lamina propria. Recently, these technological challenges have been overcome by the development of mass cytometry, which enables the simultaneous quantification of up to 40 surface and/or intracellular markers on cell subsets. We have recently adapted existing mass cytometry methodology previously employed mainly for peripheral blood cell analyses, to allow for the interrogation of intestinal lamina propria cells. We have developed, tested and optimized a panel of 37 immune cell markers that allow us to simultaneously identify all major immune cell populations, as well as numerous sub-populations, intracellular cytokines and transcription factors. Here we will prospectively assess the effects of vedolizumab on the cellular composition of intestine by performing deep immunophenotyping of immune cell subsets, prior to and after the drug’s administration. We will then determine whether changes on cell subsets correlate with clinical, endoscopic or histologic parameters of disease activity. These studies will test the validity of mass cytometry outcomes as surrogate markers for the efficacy of drugs that target lymphocyte traffic (vedolizumab, etrolizumab, anti- MAdCAM-1, ozanimod) and may directly shed light on the specific mechanism of action of these traffic-targeted therapies.


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 = -$4,844 )
2022	2020	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/30/2022	NON-COMPETING CONTINUATION	-$4,844
														Subtotal = -$4,844

Issue Date FY: 2020 ( Subtotal = $178,125 )
2020	2020	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	3/19/2020	NON-COMPETING CONTINUATION	$178,125
														Subtotal = $178,125

Issue Date FY: 2019 ( Subtotal = $213,750 )
2019	2019	VETERANS MEDICAL RESEARCH FOUNDATION OF SAN DIEGO	3350 LA JOLLA VILLAGE DR STE 151A	SAN DIEGO	CA	92161	SAN DIEGO	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/8/2019	NEW	$213,750
														Subtotal = $213,750

Grand Total All Awards = $387,031

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High Dimensional Mass Cytometry Analysis of the Effects of Vedolizumab in Intestinal Cellular Subsets and its Correlation with Clinical Parameters

Award Number: R21DK118927

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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