A5051092791- Meningioma and schwannoma management
- Parkinson's Disease Mechanisms and Treatments
- CRISPR and Genetic Engineering
- Facial Nerve Paralysis Treatment and Research
- Trigeminal Neuralgia and Treatments
- Neuroscience and Neural Engineering
- Neurofibromatosis and Schwannoma Cases
- Pituitary Gland Disorders and Treatments
- Neurological disorders and treatments
- Salivary Gland Tumors Diagnosis and Treatment
- Pluripotent Stem Cells Research
- Neurosurgical Procedures and Complications
- MicroRNA in disease regulation
- Nuclear Receptors and Signaling
- Alzheimer's disease research and treatments
- Ear and Head Tumors
- Immune Cell Function and Interaction
- Mechanical Circulatory Support Devices
- Medical Education and Admissions
- Radiomics and Machine Learning in Medical Imaging
- Myasthenia Gravis and Thymoma
- Healthcare professionals’ stress and burnout
- Neurological diseases and metabolism
- Head and Neck Surgical Oncology
- Advanced Fluorescence Microscopy Techniques
University of Pennsylvania
2020-2024
Penn Center for AIDS Research
2023-2024
University of Pennsylvania Health System
2019-2024
Wellington Hospital
2024
University of Oxford
2013-2019
National Institutes of Health
2013-2017
University of North Carolina at Chapel Hill
2013-2017
National Institute of Arthritis and Musculoskeletal and Skin Diseases
2013-2015
Center for Neuroscience and Regenerative Medicine
2013
Mayo Clinic
2011
The recent generation of induced pluripotent stem cells (iPSCs) from a patient with Parkinson's disease (PD) resulting triplication the α-synuclein (SNCA) gene locus allows unprecedented opportunities to explore its contribution molecular pathogenesis PD. We used double-nicking CRISPR/Cas9 system conduct site-specific mutagenesis SNCA in these cells, generating an isogenic iPSC line normalized dosage. Comparative expression analysis neuronal derivatives iPSCs revealed ER stress phenotype,...
α-Synuclein is critical in the pathogenesis of Parkinson's disease and related disorders, yet it remains unclear how its aggregation causes degeneration human dopaminergic neurons. In this study, we induced α-synuclein iPSC-derived neurons using fibrils generated de novo or amplified presence brain homogenates from multiple system atrophy. Increased monomer levels promote seeded a dose time-dependent manner, which associated with further increase gene expression. Progressive neuronal death...
Abstract The ability to reprogram adult somatic cells into induced pluripotent stem (iPSCs) and the subsequent development of protocols for their differentiation disease-relevant cell types have enabled in-depth molecular analyses multiple disease states as hitherto impossible. Neurons differentiated from patient-specific iPSCs provide a means recapitulate phenotypes neurodegenerative diseases in vitro . However, it remains challenging conduct precise manipulations gene expression...
Rapid and effective drug discovery for neurodegenerative disease is currently impeded by an inability to source primary neural cells high-throughput phenotypic screens. This limitation can be addressed through the use of pluripotent stem (PSCs), which derived from patient-specific samples differentiated in identifying novel compounds treatment diseases. We have developed efficient protocol culture pure populations neurons, as confirmed gene expression analysis, 96-well format necessary These...
Parkin, an E3 ubiquitin ligase, is a central mediator of mitochondrial quality control and linked to familial forms Parkinson's disease (PD). Removal dysfunctional mitochondria from the cell by Parkin thought be neuroprotective, pharmacologically increasing levels may novel therapeutic approach. We used genome-editing integrate coincidence reporter into PARK2 gene locus neuroblastoma-derived line developed quantitative high-throughput screening (qHTS) assay capable accurately detecting...
Extracorporeal membrane oxygenation (ECMO) represents a life-saving therapy in cases of refractory hypoxia and has been utilized patients suffering from the most severe forms coronavirus disease 2019 (COVID-19). A strikingly high mortality rate 94% was described early reports with COVID-19 transitioned to ECMO. Later case series demonstrating successful recovery after ECMO have revived interest this therapeutic modality, including recent approval for by Food Drug Administration (FDA). Here,...
Astrocytes are the most abundant cell type in central nervous system (CNS) and have a multitude of functions that include maintenance CNS homeostasis, trophic support neurons, detoxification, immune surveillance. It has only recently been appreciated astrocyte dysfunction is primary cause many neurological disorders. Despite their importance disease very little known about global gene expression for human astrocytes. We performed microarray analysis fetal astrocytes to identify genes...
Abstract Vestibular schwannomas (VS) are the most common tumor of skull base with available treatment options that carry a risk iatrogenic injury to facial nerve, which can significantly impact patients’ quality life. As nerve outcomes remain challenging prognosticate, we endeavored utilize machine learning decipher predictive factors relevant following microsurgical resection VS. A database patient-, tumor- and surgery-specific features was constructed via retrospective chart review 242...
α-Synuclein (α-Syn) accumulation is a pathological hallmark of Parkinson's disease. Duplications and triplications SNCA , the gene coding for α-Syn, cause genetic forms disease, which suggests that increased α-Syn dosage can drive PD. To identify proteins regulate we previously performed screen potentially druggable genes led to identification 60 modifiers. Among them, Doublecortin-like kinase 1 (DCLK1), microtubule binding serine threonine kinase, emerged as promising target due its potent...
Abstract CD4 Th cells are critical to the development of coordinated immune responses infections and tumors. activated through interactions TCR with MHC class II complexed peptide. T cell activation is dependent on density peptide complexes as well duration interaction APCs. In this study, we sought determine whether peptides could be modified amino acid sequences that facilitated uptake presentation goal improving in vitro vivo. A model epitope derived from murine folate receptor α, a self-...
Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an incisionless therapy for the treatment of medication-resistant essential tremor. Although its safety and efficacy has been demonstrated, MRgFUS typically performed with patient awake, intraprocedural neurological assessments to guide lesioning.To report first case under general anesthesia in a whose medical comorbidities prohibit him from being supine position without secured airway.The dentatorubrothalamic tract was...
Abstract Objective Spontaneous temporal encephaloceles (STEs) are increasingly recognized as sequelae of idiopathic intracranial hypertension (IIH), which in turn may further complicate their management. We endeavored to review the University Pennsylvania institutional experience on operative management STEs, with a focus factors influence surgical outcomes, particularly IIH. Design Retrospective chart over 9 years from 2013 2022. Setting Single-center, two-hospital, tertiary care, academic...
Introduction: Pituitary adenomas have recently been proposed as a barometer for health care access in the United States, given recognition that insurance status impacts diagnosis, treatment, and outcomes affected patients. Growth hormone (GH)-secreting pituitary causing acromegaly represent rare subset of this condition, possessing high socioeconomic burden due to multiple downstream effects GH on cardiovascular metabolic systems. Patients with functioning tumors are thought present before...
Introduction: Trigeminal neuralgia (TN) is a debilitating pain disorder with roughly 10,000 to 15,000 new cases diagnosed in the United States each year. Microvascular decompression (MVD) recognized as most long-lasting treatment for TN caused by blood vessel compression. However, 80% success rate and increased risk relative alternate treatments (radiosurgery, ablation techniques) it remains an important challenge predict which patients will benefit from this considerably more invasive approach.
Introduction: Sociodemographic determinants of healthcare outcomes are well documented across many fields surgical diseases. We investigated the impact race, gender, and median household income on costs patients undergoing endonasal endoscopic pituitary surgery to determine role these determinants.
Heman-Ackah, Sabrina M.; Ironside, Natasha; Quick, Mark; Bird, Philip; Boet, Ronald Author Information
Burnout, decreased professional fulfillment, and resultant attrition across the medical professions are increasingly recognized as threats to sustainable cost-effective healthcare delivery. While skill level of leaders perceived by their direct reports has been correlated with rates burnout no studies, our knowledge, have directly evaluated whether intervention via leadership training impacts fulfillment among reports. The goal this study was evaluate effectiveness a on reports' perceptions...