A5009782160- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Single-cell and spatial transcriptomics
- Immune Response and Inflammation
- Nerve injury and regeneration
- Atherosclerosis and Cardiovascular Diseases
- Eosinophilic Esophagitis
- IL-33, ST2, and ILC Pathways
- Amyotrophic Lateral Sclerosis Research
- Asthma and respiratory diseases
- MicroRNA in disease regulation
- Barrier Structure and Function Studies
- Molecular Biology Techniques and Applications
University of Pittsburgh
2022-2024
Boston Children's Hospital
2018-2024
Harvard University
2021
Microglial-derived inflammation has been linked to a broad range of neurodegenerative and neuropsychiatric conditions, including amyotrophic lateral sclerosis (ALS). Using single-cell RNA sequencing, class Disease-Associated Microglia (DAMs) have characterized in neurodegeneration. However, the DAM phenotype alone is insufficient explain functional complexity microglia, particularly with regard regulating that hallmark many diseases. Here, we identify subclass microglia mouse models ALS...
Immunomodulation holds therapeutic promise against brain injuries, but leveraging this approach requires a precise understanding of mechanisms. We report that CD8+CD122+CD49dlo T regulatory-like cells (CD8+ TRLs) are among the earliest lymphocytes to infiltrate mouse brains after ischemic stroke and temper inflammation; they also confer neuroprotection. TRL depletion worsened outcomes, an effect reversed by CD8+ reconstitution. The CXCR3/CXCL10 axis served as brain-homing mechanism for TRLs....
Abstract A key aspect of nearly all single cell experiments is the necessity to dissociate intact tissues into suspensions for processing. While many protocols have been optimized optimal yield, they often overlooked effects that dissociation can on ex vivo gene expression changes during this process. Microglia, brain’s resident macrophages, are a highly dynamic population extremely sensitive their microenvironment and shown dramatically alter transcriptome upon stimulation. We demonstrate...
Microglia, the resident immune cells of brain, rapidly change states in response to their environment, but we lack molecular and functional signatures different microglial populations. In this study, analyzed RNA expression patterns more than 76,000 individual microglia during development, old age after brain injury. Analysis uncovered at least nine transcriptionally distinct states, which expressed unique sets genes were localized using specific markers. The greatest heterogeneity was found...
A recent study by Bisht, Okojie, and Sharma, et al. characterizes a population of capillary-associated microglia (CAM) whose cell bodies are positioned along small blood vessels in the healthy mouse brain. Through elegant, longitudinal intravital imaging brain vasculature CAMs, authors have uncovered significance cerebral flow regulation. Further investigation into functions this CAM how they interact with surrounding cells within neurovascular unit will improve our understanding vascular...
Brain microglia and infiltrating monocyte-derived macrophages are vital in preserving blood vessel integrity after stroke. Understanding mechanisms that induce immune cells to adopt vascular-protective phenotypes may hasten the development of stroke treatments. IL-33 is a potent chemokine released from damaged cells, such as CNS glia The activation IL-33/ST2 signaling has been shown promote neuronal viability white matter ischemic impact on blood-brain barrier (BBB) integrity, however,...