MIBI employs secondary ion mass spectrometry to image antibodies tagged with metal reporters, thus avoiding the spectral overlap of fluorophores and allowing high dimensional single-cell phenotyping that retains the spatial organization of complex tissue samples. Our lab focuses on the development of this technology including instrumentation, development of in situ hybridization (ISH) platforms for MIBI, and computational tools for image analysis.
Computational Tools for Image Analysis
In addition to development of technologies for highly multiplexed imaging, our lab works on the application and development of analytical tools to harness both the high-dimensional single-cell phenotypic data and spatial information obtained with MIBI. Current projects include data extraction & processing, improvement of automated cell segmentation methods, and spatial analysis of tissue architecture & cellular niches. We are also developing analytical workflows for other spatial technologies, including glycan imaging and spatial transcriptomics
Tumors & the Immune Microenvironment
The immune system plays a critical role in modulating cancer progression. However, knowledge of the composition, phenotype, organization, and interactions between immune cells and tumor cells is limited. Our lab applies multiplexed imaging to study the interplay between the tumor and the immune system in order to probe tumor-immune interactions that may be therapeutically relevant. Current areas of focus include triple negative breast cancer (TNBC), ductal carcinoma in situ (DCIS), melanoma, and glioblastomas.
Little is known about the regulation of the maternal immune response to the fetus. We aim to use spatial technologies to delineate immune cell populations and their spatial organization in order to reveal the pathways that lead to spiral artery remodeling and induction of the regulatory immune response to the fetus. In addition to addressing a basic question in reproductive biology - why does the maternal immune system not attack the fetus - this research also aims to address obstetric complications related to immunological responses such as preeclampsia and preterm birth.
Tuberculosis (TB) granulomas exhibit a high degree of variability due to their histological subtypes, variable bacterial burden, and range of infection outcomes. Disparate infection outcomes are thought to be driven by underlying differences in the phenotype and histologic organization of immune cells within the granuloma. We are using spatial technologies to define immune cell populations, their phenotypes, and histologic organization within granulomas across the disease spectrum of TB. These results will enable deep characterization of the heterogeneous immune response to TB and may identify critical immune pathways for that could be targeted therapeutically.
The Brain & Alzheimer's Disease
Alzheimer’s disease (AD), a leading cause of disability and death in the US, is a major global public health problem due to an aging population. Our lab is utilizing MIBI to determine the high dimensional cellular and sub-cellular protein-level expression, interaction, and localization for AD-relevant molecules identified by genomic and proteomic studies in resilience and pathologic states of dementia and AD. Furthermore, these studies will further characterize the contribution of the immune system to normal and diseased brain function.
The gastrointestinal (GI) tract is a major interface for simultaneous protection against harmful pathogens and tolerance of commensal microbes along with food antigens. Our lab is utilizing MIBI to probe the mechanisms involved in IgE mediated peanut allergy, an example of when this interface fails to tolerate innocuous antigen. By analyzing GI biopsies from individuals undergoing oral immunotherapy to treat their allergy, we hope to understand the immunological mechanisms involved in desensitization.