03/25/2024
By Rasha El Ghazal
The Francis College of Engineering, Department of Biomedical Engineering, invites you to attend a doctoral dissertation proposal defense by Rasha El Ghazal on “Phenotypic screening of FDA approved compounds using an in vitro inflammatory nociception model comprised of hiPSC derived sensory neurons and glia on micro electrode array to identify lead analgesics.”
Candidate Name: Rasha El Ghazal
Degree: Doctoral
Defe
nse Date: Friday, April 5, 2024
Time: 10 a.m. to noon
Location: Perry Hall 315
Those interested in attending should contact Rasha_ElGhazal@student.uml.edu and committee advisor, Bryan_Black@uml.edu, at least 24 hours prior to the defense to request access to the meeting.
Committee:
- Bryan Black, Ph.D., Assistant Professor, Biomedical Engineering, University of Massachusetts Lowell
- Chiara Ghezzi, Ph.D., Assistant Professor, Biomedical Engineering, University of Massachusetts Lowell
- Suzanne Marcia Marcel Young, Ph.D., Associate Teaching Professor, Chemistry, University of Massachusetts Lowell
- Seongkyu Yoon, Ph.D., MBA, Professor, Chemical Engineering, University of Massachusetts Lowell
Brief Abstract:
Currently, 1 in 5 Americans suffer from chronic pain. It is associated with reduced quality of life due to physical disabilities and mental health problems such as depression and anxiety. Additionally, chronic pain burdens both individuals and government with substantial economic costs from medical bills, disabilities compensation, and loss of productivity; costing upwards of half a billion dollars annually. As of today, there are no treatments for chronic pain, only pain management options ranging from mind and body connection, group therapy, physiotherapy, and limited pharmacological option such as NSAIDs, corticosteroids, tricyclic antidepressants, and opioids. One challenge in developing new analgesics is the reliance on the identification of “druggable” targets. This has led to a broadcast call from the National Institutes of Health (NIH), through the Helping End Addiction Long-term (HEAL) Initiative, and the National Center for Advancing Translational Science (NCATS) for the rapid development of microphysiological systems that may be used to screen drugs in a way that does not require a detailed understanding of the pathology or assumptions regarding a compound’s mechanism(s) of action. Phenotypic screening, an alternative to druggable target-based screening, exploits a pathophysiologically-relevant phenotypic trait to simulate disease progression and/or treatment. At the Pain Research Lab, we developed a phenotypic screening assay that is comprised of human induced pluripotent stem cell (hiPSCs) derived sensory neurons and glia co-cultured on microelectrode arrays. In a previous publication, we showed that our model is an excellent stand-alone assay, based on the modified Z’ metric (an assay quality metric) with a score of 0.61. We publish on a preliminary screening with 15 FDA approved compounds known to affect targets within the pain pathway, where 10 of 15 were identified as hits. I propose to utilize our model to screen a small chemical library of FDA approved compounds and identify a lead analgesic compound. The project will be carried out based on the following aims: (1) phenotypically screen 100 FDA approved compounds known to work on targets involved in the development and maintenance of chronic pain, (2) conduct dosing and cytotoxicity assessment on hits and assess dysregulated transcripts and proteins, (3) identify one lead compound that will undergo target deconvolution to validate its analgesic mechanism of action.