The Schuele lab works on gene discovery and novel stem cell technologies to generate stem cell models from patients with Parkinson’s disease to understand the underlying causes of neurodegeneration and to develop biomarkers and new therapies for Parkinson’s disease.
Genetics program and gene discovery
We have an ongoing program to ascertain familial and sporadic cases of PD for genetic studies through our Clinical Center. We are currently treating estimated 1,500 patients per year. At this point, our database and DNA bank includes over 1000 samples from patients with PD and controls and we have identified over 200 families with two or more affected individuals with PD. The overarching goal is to identify new genes or mutations that help us to better understand the factors leading to disease and to possibly genetically categorize patients better for clinical interventions.
Modeling Parkinson’s disease in-a-dish
Skin-derived human stem cells build the foundation for studies in vitro. Patient-derived stem cells can be differentiated into neurons, specifically neurons that produce and release dopamine resembling the neurons that die in the brain of Parkinson’s patients. This unique human cellular model allows replicating conditions as in the human brain. These neurons are also electrically active and can ”fire” action potentials.
We have collected over 80 skin cell lines from donors with disease including PD, multiple system atrophy (MSA), and progressive supranuclear palsy (PSP), genetic carriers of the most common mutations in the SNCA, LRRK2, PARKIN, PINK1, and GBA genes, sporadic cases, and matched healthy controls. This is a unique collection invaluable for studying mechanisms of Parkinson’s disease.
With these novel stem cell-derived neuronal model systems, living human dopamine neurons can be manipulated and studied for changes leading to neurodegeneration. This modeling approach has great promise for advancing science and discovery by having the tools to study early changes in the disease process as well as understanding environmental exposure.
Patient specific fibroblast derived from skin biopsy.
Fibroblast are reprogrammed into induced pluripotent stem cells (iPSCs) via reprogramming factors.
iPSCs have the potential to be differentiated into a variety of different cell types. This image is of dopaminergic neurons.
Patient-Specific Induced Pluripotent Stem Cells for Disease Modeling
Recent groundbreaking discoveries allow us to transduce adult human skin cells with specific genes to generate cells that exhibit characteristics of embryonic stem cells.
Disease modeling of Parkinson's disease includes:
Derivation of patient specific iPSC lines
Optimizing neuronal differentiation
Genetic engineering of iPSC lines
Clinical Genetic Studies
The neurogenetics program at the Parkinson’s Institute includes clinical genetic studies of over 120 families afflicted with Parkinson’s disease as well as several prospective case-control studies. This rich patient population and over 1000 DNA and tissue samples built the core and basis for gene discovery, functional phenotype analysis, and biomarker studies
Biomarker discovery in patient-derived samples
Michael J Fox Foundation LRRK2 consortium
Tutorial, Videos and Protocols
A collection of protocols and video tutorials from the Schuele Lab. Protocols may be used for training and educational purposes to educate on stem cell cultures and disease modeling.
In addition the Schuele lab has provided many students the opportunity to build cell culture skills through internships, including the Stem Cell Internships in Laboratory-based Learning (SCILL) program. View posters from past SCILL students.