Research focus of my lab is to use novel synthetic biology approaches to manipulate conventional and memory-like Natural Killer (NK) cells to enhance their anti-tumor function. Using advanced CRISPR and non-CRISPR based gene editing approaches we are developing novel secondary arming strategies aimed at overcoming highly immunosuppressive TME particularly in the solid tumor setting. We are also developing novel TCR-mimetic CARs against liquid and solid malignancies with otherwise limited tumor specific antigen expression on the cell surface. 

Major projects in our lab include:

 a) TCR-mimetic CAR NK cells for targeting cancer specific neo-antigens
 b) Mesothelin CARs with secondary arming for ovarian, pancreatic and lung cancer
 c) STING modulation in the TME to enhance NK cell CAR function  
 e) CRISPR based gene editing for enhanced NK cell function
 f) Multiplex CRISPR edited iPSC derived NK cells for enhanced tumor immunotherapy
 g) Checkpoint targeted CARs to overcome tumor tolerance in advanced malignancies
 h) Novel peptide delivery system to the immune-suppressive tumor microenvironment 
 j) Development of nanoparticle based approaches to the immune cell gene editing

We have recently started early phase clinical trials of engineered memory-like NK cells in combination with novel immune-modulatory agents in patients with advanced malignancies including AML, MDS, platinum refractory head and neck cancer and multiple myeloma. Using flow cytometry, mass cytometry and single cell RNA sequencing on the samples collected from these studies allows us to study key aspects of the in vivo biology of the adoptively transferred memory-like NK cells and their interaction with other immune cells present in the tumor microenvironment. We hope this information will guide us in designing future NK cell based clinical protocols.