Khalil N. Bitar, PhD
Khalil N. Bitar, PhD, AGAF, Professor
Dr. Khalil N. Bitar grew up in Beirut, Lebanon. After graduation from the American University of Beirut (AUB), he pursued a career in Neurogastroenterology. He obtained his Masters in Physiology with emphasis on neurophysiology from the Universite de Provence (Marseilles, France) under Professeur Claude Roman and trained with Professeur Noel Mei at the Centre National de la Recherche Scientifique (CNRS) at the Institut De Neurophysiologie Vegetative (INP1). After obtaining his PhD in 1976, Dr. Bitar immigrated to the USA, trained with Dr Gabriel Makhlouf at the Medical College of Virginia and became a faculty member there. Dr. Bitar then moved to the University of Michigan where he spent 22 years directing the GI molecular motors laboratory at the Medical School. He has received several awards, including the Research Scientist Achievement Award and the League of Research Excellence from the University of Michigan, and was inducted as a Fellow of the American Gastroenterological Association.
SYNOPSIS OF AREA OF INTEREST: Dr. Bitar is the director of the Gastrointestinal (GI) Program at WFIRM. The GI program is a translational program that utilizes regenerative medicine approaches to potentially treat patients with deficiencies in the physiological functions of the GI tract. The program will utilize basic science information and apply it to the bioengineering and implantation of functional GI constructs generated from autologous cells. The program goals are intended to help pediatric, adult and geriatric patients.
SPECIFIC INTERESTS ARE:
- To study signal transduction pathways involved in gastrointestinal smooth muscle cells, and in particular, to examine agonist-induced recruitment of signal transduction molecules to the membrane of these cells
- To study thin filament regulation of smooth muscle activity and provide a regenerative medicine approach to the treatment of gastric motility disorders in an ever expanding aging population.
- To develop regenerative medicine approaches to manufacture replacement parts for the human gastrointestinal tract. This has already resulted in manufacturing of different components:
- Development of a 3-dimensional physiological model of the internal anal sphincter (IAS) and colon, bioengineered in-vitro from isolated circular and sphincter smooth muscle cells.
- Generation of 3-D bioengineered sheets (2x4 cm) of longitudinal smooth muscle.
- Successful co-culture of bioengineered IAS and colon circular constructs with enteric progenitor neural crest cells. The enteric neural progenitor cells differentiate and are able to express VIP and acetylcholine.
- Generation of in vitro bioengineered constructs with intrinsic enteric innervations that are able to generate force and respond to electrical field, cholinergic, and relaxant (VIP) stimulation, indicating the integrity of receptors and neural release of neurotransmitters.
- Successful implantation (in situ) of constructs with intrinsic neural innervations generated from mouse IAS into sibling mice, and of human muscle and neural progenitor cells in athymic rats. These constructs were not rejected after implantation and preserved all the functions they had before implantation.
- We have preliminary results indicating that bioengineered constructs from human IAS cells were able to co-culture with progenitor enteric neural cells. These human constructs were implanted successfully under the skin and in situ in nude mice. The bioengineered constructs were not rejected and were able to maintain all the characteristics of IAS.
These proofs of concept reinforce a strong belief that this direction of our research offers new insight and possible therapeutic models (either direct injection or autologous implantation) for GI motility (fecal incontinence, sluggish motility associated with aging, LES) and possibly urinary incontinence. This also offers a new outlook for providing a better quality of life to children afflicted with aganglionic disorders (e.g., Hirschprung’s disease).