Robert Wood Johnson Medical School
Department of Medicine
The Cancer Institute of NJ
195 Little Albany Street, Room 4562
New Brunswick, NJ 08901
Stem cells, cell cycle regulation and zebrafish models for drug discovery
The research efforts in the Sabaawy laboratory are focused on targeting normal and tumor stem cells during malignant transformation using the zebrafish animal model. These studies aim to dissect stem cell developmental pathways subverted in normal stem cell development, and how cancer stem cells divert from these regulatory pathways. A powerful attribute of the zebrafish is its capacity for performing large-scale forward genetic screens on transparent, readily accessible embryos. Using modifier screens in conjunction with transgenic approaches, the laboratory is generating new conditional transgenic zebrafish models of several different cancers, including the major subtypes of human myeloid and lymphoid leukemias, lymphoma, and sarcoma. The laboratory has generated zebrafish with the t(12;21) translocation that develop leukemias similar to human pre-B ALL. The laboratory is conducting a modifier screen to identify both enhancers and suppressors of pre-B-cell leukemia. Chemical and genetic modifier screens using tumor-prone zebrafish lines may ultimately reveal mutant genes or drugs that can suppress or modify disease progression, and will be validated in human trials. Additionally, the laboratory is collaborating with several CINJ investigators to utilize zebrafish in human tumor initiating cell xenotransplants, in an effort to predict the tumor response to therapy in a personalized medicine approach. Through the combination of translational and drug discovery strategies, we hope to uncover novel genes and targets for the development of small molecule inhibitors that are more effective as cancer therapies.
A parallel research effort in the laboratory is to study human mesenchymal stroma cell (MSC)-based therapy and transplantation in regenerative medicine. Cell therapy using stem cells for regeneration of a failing organ or injury repair is a promising approach. Dr. Sabaawy and his colleagues are collaborating on international trials for utilizing MSCs cell therapy for injury repair.