David Pitt, MD
Associate Professor of NeurologyCards
About
Research
Overview
Multiple Sclerosis (MS) is a common inflammatory disease of the central nervous system. MS has a prominent, neurodegenerative component that is most visible in the progressive phase of the disease. Neurodegeneration in MS is poorly understood and currently not treatable. Our research goal is to decipher the molecular and cellular mechanisms of MS-related neurodegeneration and to translate these insights into therapies.
Defining the Contribution of Astrocytes and Oligodendrocytes to Genetic MS Susceptibility
We are systematically identifying the MS risk variants that are active in astrocytes and oligodendrocytes and the genes that they perturb. For this, we are generating chromatin accessibility profiles of astrocytes/oligodendrocytes isolated from MS lesions and intersect these profiles with MS risk variants. The resulting list of variants and variant-dependent genes will provide a roadmap of astroglia/oligodendroglia pathways that are dysregulated by MS risk variants and are ikely to contribute to glia-mediated MS susceptibility.
Identifying Cellular Phenotypes and Generate Spatial and Functional Maps of their Interactions in MS Lesions
We are combining single nuclear RNA sequencing (sNuc-Seq) of MS lesion tissue with highly multiplexed tissue imaging to identify and localize cellular subpopulations within MS lesions and determine their molecular interactions. We are thus generating spatial and functional maps that provide unprecedented insight into the in situ-funcionality of lesional cellular subpopulations.
Astrocyte-Derived Exosomes as Biomarkers for MS Progression and Remyelination
Current MS research focuses increasingly on disease progression and myelin repair, and there is a surge of clinical trials that test potentially neuroprotective or remyelinating compounds. These trials face the fundamental challenge that MS progression and remyelination are difficult to quantity in vivo. We are exploring the potential of astrocyte-derived exosomes to monitor and predict disease progression, remyelination and treatment responses.
Innovative Techniques in our Lab include:
· Highly multiplexed imaging: Individual, histological sections are labeled with 40+ antibodies to capture cellular subpopulations in MS lesions, place them within the context of the lesion environment, and identify their specific interaction networks.
· Computational pipeline (Ilastik, CellProfiler, histoCAT, PHATE, and Pseudotime) for cellular segmentation, identiication o cellular phenotypes, and spatial analysis.
· Purification of astrocyte and oligodendrocyte nuclei from MS, Alzheimer's, and Parkinson's tissue for transcriptomal and genomic profiling with sNuc-Seq and ATAC-Seq.
· CRISPR/Cas9 genome editing of MS patient-derived iPSCs.
· Generation of iPSC-derived astrocytes.
· Purification and quantification of exosomes from patient plasma.
Medical Subject Headings (MeSH)
Academic Achievements and Community Involvement
Clinical Care
Overview
David Pitt, MD, is a neurologist specializing in multiple sclerosis (MS) and other neuro-inflammatory diseases at Yale Medicine.
Dr. Pitt spends the majority of his time as a researcher, investigating the causes of neurodegeneration in MS. He is also working on a new imaging method to make inflammation visible in the brain so that doctors can adjust the way they treat MS at different stages of the disease. His research into the biological mechanisms behind MS informs his work as a physician.
When seeing patients, Dr. Pitt values taking the time to educate them about the nature of MS and how the scientific knowledge and treatments of the condition have substantially improved over the years. “The reputation of MS as a terrible disease lags behind how well we can treat it nowadays,” he says.
“I find it important to explain to newly diagnosed patients what it really means to have multiples sclerosis and how this might be different from their conception of what it is.”
In addition to treating patients and conducting research, Dr. Pitt is an associate professor of Neurology at the Yale School of Medicine.
Clinical Specialties
Fact Sheets
Multiple Sclerosis (MS)
Learn More on Yale MedicineAdvanced Imaging for Multiple Sclerosis
Learn More on Yale MedicineCarotid Artery Disease Imaging
Learn More on Yale MedicineMeningitis
Learn More on Yale Medicine
Board Certifications
Neurology
- Certification Organization
- AB of Psychiatry & Neurology
- Latest Certification Date
- 2018
- Original Certification Date
- 2007
Yale Medicine News
Links & Media
Media
News
- May 05, 2023
9 Yale Neurologists Named Connecticut's 'Top Doctors'
- December 16, 2018
Gene Variant Found in Brain Complicit in MS Onset
- March 03, 2013
Yale’s clinical practice welcomes its newest physicians