Dissertation Defense: Faris Alkhilaiwi

Candidate Name: Faris Alkhilaiwi

Major: Biochemistry and Molecular & Cellular Biology

Advisor: Richard Schlegel, M.D/Ph.D.

Title: The Application of Conditional Reprogramming to Drug Discovery and Regenerative Medicine

The Conditional Reprogramming (CR) method has been shown to induce an in vitro stem-like state allowing for the continuous growth of patient derived epithelial cells. Due to this new culture system, it has been possible to identify potential therapies for multiple cancer types and to generate differentiated tissue from cultures of normal epithelia cells. Hence, CR has broad applications in the field of drug discovery and regenerative medicine.

Based upon the above findings, we evaluate the ability of CR to identify potential drugs to treat a rare but morbid disease called recurrent respiratory papillomatosis (RRP). Robotic high-throughput screening was performed in collaboration with the National Center for Advanced Technology (NCATS). The conditionally reprogrammed cells, GUMC-403 cells, were screened against two libraries of >4700 drugs. From the two libraries, we identified a total of 13 drugs that induced substantial cytotoxicity in GUMC-403. Furthermore, we validated the efficacy of the drugs in vitro using 2D and 3D models and further polished our list of drugs to panobinostat, dinaciclib and forskolin as potential treatments for RRP patients.

On another front, we investigated the ability of Conditional Reprogramming to propagate equine keratinocyte cultures for long-term expansion. 3D air-liquid interphase culture was used to investigate the ability of CR equine keratinocytes to differentiate and form stratified squamous epithelium that was positive for terminal differentiation markers. These unlimited supplies of autologous cells could be used to generate skin transplants without the risk of immune rejection.

Our work indicates that conditional reprogramming is a robust method that allows for the rapid and continued in vitro propagation of primary cancer cells or normal equine keratinocytes that can be used for drug discovery or regenerative medicine respectively.

Thursday, September 13 at 11:00am to 1:00pm

Medical and Dental Building, SW 107
3900 Reservoir Road, N.W., Washington

Event Type

Academic Events, Dissertation Defense

Departments

Biomedical Graduate Education, Biochemistry and Molecular & Cellular Biology, Graduate School of Arts and Sciences

Cost

Free

Open to the public and the press?

Yes

Event Contact Name

Lucy Cherner

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