Current active projects in the Schatz lab include:

1. Tumor cell-intrinsic mechanisms of resistance to CAR-T cellular immunotherapies in diffuse large B-cell lymphoma (DLBCL). Novel genomic findings in tumors from patients who failed to respond to autologous T-cell immunotherapies permit new opportunities to understand the basis for clinical responses.
   
   
2. Mechanisms of lymphomagenesis and treatment resistance driven by recurrent mutations in DLBCL of the BCL10 signaling protein. BCL10 mutations directly activate a key signaling complex that promotes lymphoma and resistance to multiple drugs. We are developing combination drug strategies to overcome resistance.
   
   
3. Studies of the Cyclin-G Associated Kinase (GAK) as a drug-targetable critical dependency for cell cycle progression by DLBCL tumors. We are defining GAK’s mechanisms in promoting the rapid proliferation of DLBCL tumors and exploring it as a drug target, including synthesis and testing of novel inhibitors.
   
   
4. Mechanisms and therapeutic consequences of translational reprogramming in cancer cells exposed to rocaglate eIF4A inhibitors targeting oncogenic cap-dependent translation initiation. We have discovered key vulnerabilities that arise in lymphoma cells after treatment with these compounds, facilitating novel drug combinations with potent efficacy.