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Your search keyword '"Heman-Ackah, Sabrina"' showing total 24 results
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24 results on '"Heman-Ackah, Sabrina"'

2. A multi-institutional machine learning algorithm for prognosticating facial nerve injury following microsurgical resection of vestibular schwannoma

Author

Heman-Ackah, Sabrina M., primary, Blue, Rachel, additional, Quimby, Alexandra E., additional, Abdallah, Hussein, additional, Sweeney, Elizabeth M., additional, Chauhan, Daksh, additional, Hwa, Tiffany, additional, Brant, Jason, additional, Ruckenstein, Michael J., additional, Bigelow, Douglas C., additional, Jackson, Christina, additional, Zenonos, Georgios, additional, Gardner, Paul, additional, Briggs, Selena E., additional, Cohen, Yale, additional, and Lee, John Y. K., additional

Published
2024
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6. Alpha-synuclein in Parkinson's disease : molecular pathogenesis and development of genome engineering-based silencing approaches

Author

Heman-Ackah, Sabrina M. and Wood, Matthew J. A.

Subjects
616.8
Abstract

The ability to reprogram adult somatic cells into induced pluripotent stem cells (iPSCs) and subsequent development of protocols for their differentiation into disease-relevant cell types have enabled in-depth molecular analyses of multiple disease states as hitherto impossible. Parkinson's disease (PD) is one such example, in which the dopaminergic neurons that manifest pathology are embedded in an inaccessible region of the midbrain, the substantia nigra pars compacta, making it unfeasible to obtain samples of the affected region from living patients. Overabundance of alpha-synuclein, encoded by the SNCA gene, has long been implicated in the pathogenesis of PD. However, the precise mechanism by which overexpression of alpha-synuclein leads to the demise of dopaminergic neurons remains elusive. Neurons differentiated from PD patient-specific iPSCs carrying multiplications of the SNCA gene may provide a means to recapitulate molecular phenotypes of the disease in vitro. The application of CRISPR/Cas9 to mammalian systems is likewise revolutionizing the utilization of genome editing in the study of molecular contributors to the pathogenesis of numerous diseases, including PD. In this body of work, I have utilized the double-nicking CRISPR/Cas9 system to mediate site-specific mutagenesis of SNCA in PD patient-specific iPSCs harboring a triplication of the SNCA gene locus, resulting in isogenic cells which can be used to phenocopy normal alpha-synuclein expression from two alleles. I have further demonstrated the utility of nuclease null or "dead" Cas9, for transcriptional silencing of alpha-synuclein expression. Finally, I have used these systems to interrogate phenotypic outcomes of SNCA triplication, demonstrating that alpha-synuclein induces endoplasmic reticulum stress and aberrant activation of a highly conserved arm of the unfolded protein response. The tools generated in these studies can be applied in future efforts to dissect the contributions of alpha-synuclein overexpression to PD pathogenesis and as a platform for the discovery of disease-modifying therapeutic approaches for PD.

Published
2015

8. Impact of Patient Demographics and Socioeconomic Status on Surgical Outcomes in Endonasal Endoscopic Pituitary Surgery.

Author

Blue, Rachel, Miranda, Stephen P., Ajmera, Sonia, Kumar, Nankee, Alexis, Maya, Heman-Ackah, Sabrina, Salwi, Sanjana, Palmer, James N., Adappa, Nithin D., Lee, John Y.K., Grady, M. Sean, Yoshor, Daniel, and Jackson, Christina

Subjects
ENDOSCOPIC surgery, SOCIOECONOMIC status, INCOME
Abstract

This article explores the impact of patient demographics and socioeconomic status on surgical outcomes in endonasal endoscopic pituitary surgery. The study reviewed 187 patients who underwent this surgery between 2017 and 2019. The findings revealed that male patients were more likely to have larger tumors and higher comorbidity scores, while Hispanic patients had smaller tumors and lower comorbidity scores. Black patients experienced longer hospital stays, higher costs, and higher rates of readmission, regardless of income. These results suggest that racial health disparities are not solely due to socioeconomic status and emphasize the importance of considering social determinants of health in clinical practice. [Extracted from the article]

Published
2024
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19. Doublecortin-like Kinase 1 Regulates α-Synuclein Levels and Toxicity

Author

Vázquez-Vélez, Gabriel E., primary, Gonzales, Kristyn A., additional, Revelli, Jean-Pierre, additional, Adamski, Carolyn J., additional, Alavi Naini, Fatemeh, additional, Bajić, Aleksandar, additional, Craigen, Evelyn, additional, Richman, Ronald, additional, Heman-Ackah, Sabrina M., additional, Wood, Matthew J.A., additional, Rousseaux, Maxime W.C., additional, and Zoghbi, Huda Y., additional

Published
2019
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20. Doublecortin-like Kinase 1 Regulates α-Synuclein Levels and Toxicity.

Author

Vázquez-Vélez, Gabriel E., Gonzales, Kristyn A., Revelli, Jean-Pierre, Adamski, Carolyn J., Naini, Fatemeh Alavi, Bajić, Aleksandar, Craigen, Evelyn, Richman, Ronald, Heman-Ackah, Sabrina M., Wood, Matthew J. A., Rousseaux, Maxime W. C., and Zoghbi, Huda Y.

Subjects
SERINE/THREONINE kinases, PARKINSON'S disease, GENETIC code, GENETIC disorders
Abstract

α-Synuclein (α-Syn) accumulation is a pathological hallmark of Parkinson's disease. Duplications and triplications of SNCA, the gene coding for α-Syn, cause genetic forms of the disease, which suggests that increased α-Syn dosage can drive PD. To identify the proteins that regulate α-Syn, we previously performed a screen of potentially druggable genes that led to the identification of 60 modifiers. Among them, Doublecortin-like kinase 1 (DCLK1), a microtubule binding serine threonine kinase, emerged as a promising target due to its potent effect on α-Syn and potential druggability as a neuron-expressed kinase. In this study, we explore the relationship between DCLK1 and α-Syn in human cellular and mouse models of PD. First, we show that DCLK1 regulates α-Syn levels post-transcriptionally. Second, we demonstrate that knockdown of Dclk1 reduces phosphorylated species of α-Syn and α-Syn-induced neurotoxicity in the SNc in two distinct mouse models of synucleinopathy. Last, silencing DCLK1 in human neurons derived from individuals with SNCA triplications reduces phosphorylated and total α-Syn, thereby highlighting DCLK1 as a potential therapeutic target to reduce pathological α-Syn in disease. [ABSTRACT FROM AUTHOR]

Published
2020
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24. Chemogenomic Profiling of Endogenous PARK2Expression Using a Genome-Edited Coincidence Reporter

Author

Hasson, Samuel A., Fogel, Adam I., Wang, Chunxin, MacArthur, Ryan, Guha, Rajarshi, Heman-Ackah, Sabrina, Martin, Scott, Youle, Richard J., and Inglese, James

Abstract

Parkin, an E3 ubiquitin ligase, is a central mediator of mitochondrial quality control and is linked to familial forms of Parkinson’s disease (PD). Removal of dysfunctional mitochondria from the cell by Parkin is thought to be neuroprotective, and pharmacologically increasing Parkin levels may be a novel therapeutic approach. We used genome-editing to integrate a coincidence reporter into the PARK2gene locus of a neuroblastoma-derived cell line and developed a quantitative high-throughput screening (qHTS) assay capable of accurately detecting subtle compound-mediated increases in endogenous PARK2expression. Interrogation of a chemogenomic library revealed diverse chemical classes that up-regulate the PARK2transcript, including epigenetic agents, drugs controlling cholesterol biosynthesis, and JNK inhibitors. Use of the coincidence reporter eliminated wasted time pursuing reporter-biased false positives accounting for ∼2/3 of the actives and, coupled with titration-based screening, greatly improves the efficiency of compound selection. This approach represents a strategy to revitalize reporter-gene assays for drug discovery.

Published
2015
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