The research efforts in the Sabaawy laboratory are focused on studying cell biology and development in disease and cancer models utilizing single cell patient-derived organoids, single cell multiomics, 3D microenvironment cocultures, and humanized mouse and zebrafish grafts for drug discovery. We aim to dissect the genomic and epigenomic cell developmental pathways, and how tumor cells divert from the regulatory signals to identify novel therapies. One major pathway for research focus is the regulation of the cellular self-renewal by the polycomb repressor complex 1 (PRC1) member BMI1, the canonical and non-canonical BMI1-mediated chromatin effects, genomic non-coding polycomb response elements, and interactions with cell cycle and immune checkpoints during cell cycle progression and immune activation. Utilizing organoids, CRISPR- and recombinase-based genome editing, drug modifiers, and transgenic and surgical grafting approaches; the laboratory is advancing precision medicine platforms in prostate, brain, breast, and lung cancers, and leukemias.
The research in the laboratory has uncovered novel self-renewal mechanisms using genomic conditional ablation and Cas9-based genome editing and is developing small molecules targeting self-renewal and immune checkpoints for combined synergistic targeted therapies.
The current research projects in the Sabaawy laboratory include: 1) Study of genetic diversity in prostate and brain cancers using 3D organoids and mouse models, 2) Study of clonal dynamics using single cell fluorescent reporters, 3) Targeting of cellular self-renewal and immune checkpoint activity using organoid stromal cocultures and humanized mouse models, and 4) Developing functional assays for self-renewal and polycomb-mediated transcriptional repression and activation.
Patient derived organoids
We have established standard operating procedures for generating patient single cell-derived organoid models using adult stem cells and iPSCs from multiple normal and cancer tissues. We generated a growing biobank of annotated and gene profiled patient derived organoid (PDO) and corresponding patient derived xenograft (PDX) lines from prostate, lung, breast, renal, and brain cancers and normal associated tissues.
We are performing high-throughput drug sensitivity screening in these organoid models to identify compounds with best on target activity and testing combined therapy in humanized PDX and allograft models for immune oncology studies.