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Metabolomics for Determining Mechanism of Action of Botanical Medicines

Award Number: F31AT011152
ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/01/2021
PERIOD OF PERFORMANCE END DATE: 12/09/2022

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Metabolomics for Determining Mechanism of Action of Botanical Medicines - PROJECT SUMMARY The effectiveness of botanical medical therapies has been observed for centuries and has served as a source of inspiration for modern medical practice, with 25% of prescribed pharmaceuticals derived from botanicals. Yet, understanding of the complex chemical interactions and mechanisms of action of botanical natural products has remained a challenge for the scientific community. With advanced analytical chemistry instrumentation and access to systems designed for processing large datasets, we are poised to develop a metabolomics tool to predict mechanism of action of complex botanical extracts to addresses this knowledge gap. To develop this model, we will evaluate activity of botanical natural products against highly-drug resistant Acinetobacter baumannii, a common bacterial pathogen. The botanicals tested will include Viola odorata, which is known to produce antimicrobial cyclic peptides, as well as a series of other botanicals with reported activity against A. baumannii. Activity of the botanicals will be compared with that of known antibiotics and pure compounds of botanical origin. Development of a metabolomics-based mechanism of action prediction approach with be the first goal of this project, while the second goal will be comparison of the mechanism of action demonstrated by a complex botanical extract to its known constituents. Botanicals displaying a mechanism of action different than its known constituents, as informed by the metabolomics approach, will be candidates for isolation and characterization of the combination effects. Finally, a previously established in vivo model using Galleria mellonella will be employed to predict the cytotoxicity of the botanical natural products. We expect that the findings of this study will be of benefit to other investigators studying mechanisms of action for complex botanical natural products and will not be limited to antimicrobial applications. The proposed research is relevant to the National Center for Complementary and Integrative Health (NCCIH) strategic plan because it involves the investigation of alterative and complementary health practices common in the US. These studies will be conducted by a highly qualified trainee (Heather Winter) who seeks to pursue a career in biomedical research. She has already established a track record for successful research in natural products, and will benefit from the proposed training plan by expanding her experience with mass spectrometry based metabolomics methodologies and by gaining experience characterizing complex botanicals. The mentor, Dr. Nadja Cech, is Patricia A. Sullivan Professor of Chemistry at the University of North Carolina Greensboro, and has effectively mentored multiple PhD students, including trainees supported by the F31 and T32 fellowships.


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 = -$5,377 )
2024	2022	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN ST	GREENSBORO	NC	27412	GUILFORD	USA	Research and Training in Complementary and Integrative Health	000	2	10/31/2023	NON-COMPETING CONTINUATION	-$3,219
2024	2022	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN ST	GREENSBORO	NC	27412	GUILFORD	USA	Research and Training in Complementary and Integrative Health	001	2	10/31/2023	NON-COMPETING CONTINUATION	-$2,158
														Subtotal = -$5,377

Issue Date FY: 2023 ( Subtotal = -$10,364 )
2023	2022	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Research and Training in Complementary and Integrative Health	001	2	2/9/2023	NON-COMPETING CONTINUATION	$0
2023	2022	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Research and Training in Complementary and Integrative Health	000	2	2/8/2023	NON-COMPETING CONTINUATION	-$10,364
														Subtotal = -$10,364

Issue Date FY: 2022 ( Subtotal = $35,275 )
2022	2022	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Research and Training in Complementary and Integrative Health	000	2	4/21/2022	NON-COMPETING CONTINUATION	$35,275
														Subtotal = $35,275

Issue Date FY: 2021 ( Subtotal = $34,558 )
2021	2021	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Research and Training in Complementary and Integrative Health	000	1	4/1/2021	NEW	$34,558
2021	2021	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Research and Training in Complementary and Integrative Health	001	1	4/1/2021	NEW	$0
2021	2021	UNIVERSITY OF NORTH CAROLINA AT GREENSBORO	1000 SPRING GARDEN STREET	GREENSBORO	NC	27412	GUILFORD	USA	Research and Training in Complementary and Integrative Health	002	1	5/17/2021	NEW	$0
														Subtotal = $34,558

Grand Total All Awards = $54,092

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Metabolomics for Determining Mechanism of Action of Botanical Medicines

Award Number: F31AT011152

ORGANIZATION: CENTER FOR DRUG EVALUATION AND RESEARCH, NIH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/01/2021

PERIOD OF PERFORMANCE END DATE: 12/09/2022

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