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Development of Highly Multiplexed Raman Imaging Platform for Alzheimer’s Disease

Award Number: K99EB035706
ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 01/01/2025
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Development of Highly Multiplexed Raman Imaging Platform for Alzheimer’s Disease - PROJECT SUMMARY The immune system plays a significant role in aging and in autoimmune, neurodevelopmental, and neurodegenerative diseases. Functionally diverse immune cells change with disease progression and shape disease pathology through complex mechanisms. Current molecular imaging techniques do not allow for simultaneous interrogation of multiple biomarkers from a single tissue sample. In the proposed preclinical study, I will develop a nanoparticle-based Raman imaging approach capable of highly multiplexed molecular spatial profiling of brain histology sections of Alzheimer’s disease (AD) patients. There is a critical need to improve our understanding of brain immunity to offer intervention tools for designing new therapeutic strategies for treating and preventing brain pathologies. My new multiplexed imaging platform will identify and capture the underlying cellular and phenotypic diversity in intricate neural tissues within the spatial context of the brain. Sharp and unique spectral barcodes of the carefully selected ensemble of surface-enhanced Raman scattering (SERS) nanoparticles (NPs) will ensure reliable and accurate spectral unmixing. During the K99 mentored phase, I will design NP constructs exhibiting strong and unique Raman scattering signals (SA1). Unlike traditional imaging techniques, the developed SERS NPs will be capable of visualizing at least 30 biomarkers in a single imaging acquisition. I will validate the high spectral specificity and quantitative accuracy of the spectral unmixing. In SA2, the NPs will be decorated with biotargeting species to ensure highly specific recognition of immune-brain biomarkers in cell culture and tissue sections. An innovative strategy will be used to stain and image archived patient samples starting with single plex Raman imaging and correlated with the gold standard IHC histology. As an independent investigator, I will use targeted SERS NPs to produce highly multiplexed proteomic images of brain tissue. To confirm the sensitivity and specificity of the Raman imaging approach, the adjacent tissue sections will be assessed by IHC and conventional immunofluorescence imaging. These highly multiplexed molecular maps of the brain-immune spatial biology will pave the way for future studies focused on improving our ability to understand, prevent, and treat AD. I have a unique set of expertise in SERS imaging and believe I am highly qualified to lead and conduct the proposed project at the University of Southern California. I also have identified the following key areas which require additional training to support my transition to independence: (1) quantitative spectral unmixing and image processing; (2) active cell targeting; (3) histopathological evaluation of postmortem brain tissue with a solid knowledge base in AD biology. I have deliberately chosen and carefully assembled a world-class committee of mentors and advisors including my primary mentor Dr. Cristina Zavaleta and co-mentor Dr. Peter Y. Wang. My mentors are in full support of my research and career goals. I am committed to the research proposed here and strongly believe that it will help me gain the necessary training required to enable my long-term career goal of being an established investigator in the field of molecular imaging.


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: 2026 ( Subtotal = $124,562 )
2026	2026	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	2	12/15/2025	NON-COMPETING CONTINUATION	$124,562
														Subtotal = $124,562

Issue Date FY: 2025 ( Subtotal = $124,562 )
2025	2025	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Discovery and Applied Research for Technological Innovations to Improve Human Health	000	1	12/16/2024	NEW	$124,562
														Subtotal = $124,562

Grand Total All Awards = $249,124

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Development of Highly Multiplexed Raman Imaging Platform for Alzheimer’s Disease

Award Number: K99EB035706

ORGANIZATION: NATIONAL INSTITUTE Of BIOMEDICAL IMAGING & BIOENGINEERING

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 01/01/2025

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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