Cellular Neurochemistry
Our team focuses on mapping the role local tissue/cell microenvironments have on homeostasis and pathological changes, in healthy and diseased human brain. We work at the cross section of molecular neurobiology and analytical chemistry. In our projects, we incorporate tissue, complex stem cell-derived model systems, and brain tumor cultures. To understand the contribution of single cells to broad disease phenotypes, we use spatially resolved chemical and molecular imaging approaches (such as mass spectrometry imaging).
Development of scalable approaches to study single-cell metabolic phenotypes
High throughput phenotyping approaches offer the possibility to broaden our understanding of the fundamental cellular changes across diverse aspects of human health. Their application includes conventional drug screening and assessment of the effects environmental factors have on the cell states. This project aims to develop and employ high throughput multi-omic phenotyping approaches to understand the fundamental metabolic changes of distinct neuronal and glial cell populations in the human brain. For this work, we develop and employ single-cell/cell-subtype analysis approaches, focus on the role of central bioenergetic pathways, and study the role of these pathways in development and aging.
Study of dynamic metabolic changes among brain tumors, and their microenvironment
Tumor cells exhibit alterations in their metabolism. These changes support their uncontrolled growth, proliferation, and metastasis. While selectively targeting such changes in tumor cell metabolism appears to be an attractive approach to target tumor cells, many metabolism-targeting drugs fail in clinical trials. Among other reasons, we still have insufficient knowledge about metabolic vulnerabilities of the surrounding non-cancer cells, and the supportive role this complex microenvironment can play in tumor progression. This project aims to, at a single cell level, investigate the precise metabolic profile of diverse forms of brain tumors and their interplay with local microenvironments, in a brain region-specific fashion. This is done by employing advanced co-cultures of human brain region-specific 3D models and 3D tumor models, and characterizing them through cutting-edge dynamic metabolic/lipidomic phenotyping and lineage mapping.
Targeting vascular complications in Alzheimer’s disease (immuno and gene) therapies
Intravenous delivery of FDA-approved antibody-based therapies for probable Alzheimer disease (AD) dementia can result in severe complications, such as edema or microhemorrhages. These complications are often referred to as amyloid-related imaging abnormalities (ARIA). Radiologically ARIA is similar to cerebral amyloid angiopathy-related inflammation (CAA-RI). The inflammation associated with both phenomena (ARIA and CAA-RI) are poorly understood. This project aims to characterize how differences in CAA Aβ isoform composition influence vascular-immune cell populations/interactions. Further, we aim to understand the effects antibody-based treatments have on CAA, local cellular and molecular microenvironment, both in short- and long-term treatments.