Harvard Catalyst Profiles

The interplay between the brain and the immune system plays critical roles in the pathogenesis of many debilitating conditions, including Alzheimer’s disease. This intricate crosstalk between the nervous and immune systems can have either beneficial or harmful effects on brain function, depending on the context. Our lab recently found that CD8+ T cells shape the brain by infiltrating and activating glial cells, which leads to exacerbation of neuroinflammation and neurodegeneration. This biological misstep exacerbates various brain disorders, depending on the timing and location of the occurrence. Understanding the mechanisms governing these diverse outcomes is crucial. Our research sits at the intersection of neuroscience, immunology, and engineering. The ultimate goal is to understand the critical signaling between brain cells and the immune system and how these processes are disrupted in neurological disorders. To achieve this, we employ innovative microfluidic systems, stem cells, and various profiling techniques (transcriptomic, proteomic, and functional) to precisely measure biological processes in cells. Skills required: We welcome students with basic biology lab skills to apply, and no prior research experience is necessary. Selected students will receive training in lab techniques under the guidance of senior scientists. Learning outcomes: Students involved in the project will gain research skills, including study design, data analysis methods, presentations, and scientific writing. Additionally, they will acquire wet lab skillsets such as brain-on-chips, cell culture, stem cells, neuronal and glia differentiation, brain barriers modeling, immune cell isolation (e.g., T cells and monocytes), immunofluorescence staining, confocal imaging, MSD/ELISA assays, flow cytometry, qPCR, western blot, and experience working in a lithography clean room to engineer microfluidic systems. Length of the project: Flexible, ranging from 6 to 12 months. Mentoring: Students will be mentored by senior lab members, including postdocs. The PI will also have regular weekly meetings with students.

Multiple sclerosis (MS) is a debilitating central nervous system (CNS) inflammatory disease involving a complex interplay between CNS resident cells and inflammatory peripheral immune cells. Progressive forms of MS pose a significant challenge due to the limited effectiveness of current therapies that target immune cells in Relapsing-Remitting MS. Thus, there is a critical need for a better understanding of the mechanisms by which progressive MS develops. Our research sits at the intersection of neuroscience, immunology, and engineering. The ultimate goal is to understand the critical signaling between brain cells and the immune system, how these processes are disrupted in progressive MS, and identify novel pathological mechanisms and potential therapeutic targets. To achieve this, we employ innovative microfluidic systems, stem cells, immune cells from MS patients and various profiling techniques (transcriptomic, proteomic, and functional) to precisely measure biological processes in cells. Skills required: We welcome students with basic biology lab skills to apply, and no prior research experience is necessary. Selected students will receive training in lab techniques under the guidance of senior scientists. Learning outcomes: Students involved in the project will gain research skills, including study design, data analysis methods, presentations, and scientific writing. Additionally, they will acquire wet lab skillsets such as brain-on-chips, cell culture, stem cells, neuronal and glia differentiation, brain barriers modeling, immune cell isolation (e.g., T cells and monocytes), immunofluorescence staining, confocal imaging, MSD/ELISA assays, flow cytometry, qPCR, western blot, and experience working in a lithography clean room to engineer microfluidic systems. Length of the project: Flexible, ranging from 6 to 12 months. Mentoring: Students will be mentored by senior lab members, including postdocs. The PI will also have regular weekly meetings with students.

Barrier interfaces play crucial roles in both maintaining healthy brain function and contributing to disease states. Specifically, dysfunction of the blood-brain barrier (BBB) has been implicated in the development of various neurodegenerative diseases like Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). However, our comprehension of the functioning of barrier interfaces in the brain, including the BBB and blood-CSF barrier in the choroid plexus, is hindered by the lack of human cellular models that faithfully replicate their intricate structure and function. To address this, our lab is modeling and studying barrier interfaces to better understand the complexities of healthy brain function and identify deviations in disease states, such as Alzheimer’s. Our approach involves incorporating iPSC-derived brain endothelial cells, pericytes, astrocytes, and neurons into microfluidic systems. We also use CRISPR-mediated genome editing to introduce specific causal and risk mutations into iPSCs to facilitate cross-comparisons between genotypes and the creation of allelic libraries within similar genetic backgrounds. Ultimately, our goal is to gain insights into the critical signaling between brain cells and brain barriers and understand how these biological processes are disrupted in neurological diseases. Skills required: We welcome students with basic biology lab skills to apply, and no prior research experience is necessary. Selected students will receive training in lab techniques under the guidance of senior scientists. Learning outcomes: Students involved in the project will gain research skills, including study design, data analysis methods, presentations, and scientific writing. Additionally, they will acquire wet lab skillsets such as brain-on-chips, cell culture, stem cells, neuronal and glia differentiation, brain barriers modeling, immune cell isolation, immunofluorescence staining, confocal imaging, MSD/ELISA assays, flow cytometry, qPCR, western blot, and experience working in a lithography clean room to engineer microfluidic systems. Length of the project: Flexible, ranging from 6 to 12 months. Mentoring: Students will be mentored by senior lab members, including postdocs. The PI will also have regular weekly meetings with students.