The Lucas Lab's research interests include inherited human immune disorders, genomics, proteomics, post-translational modifications, phosphoinositide 3-kinase (PI3K), Antigen Receptor signal transduction, T cell senescence, cell death, inflammation, targeted therapies.
Our studies begin with patients suffering from inherited immune disorders and utilize various approaches to uncover the genetic and biochemical defects responsible for disease with the goal of applying this knowledge not only to devise targeted therapies for rare disorders but also to more generally dissect basic pathways critical for adaptive immunity. We aim to identify novel signaling pathways using unbiased approaches including not only genomics but also phosphoproteomics with mass spectrometry to address questions related to human T cell biology (e.g., regulation of TCR-induced cell death, terminal differentiation, telomere length and cellular senescence/DNA damage responses). A major current focus of the lab is on phosphoinositide 3-kinase (PI3K) signaling and mechanisms of disease in patients with inherited mutations in PI3K subunits.
What We've Achieved
- Collaborative discovery of a novel human primary immunodeficiency (PASLI/APDS) caused by germline mutations that hyperactive PI3Kdelta
- Identification of new, N-terminal mutation sites in the gene encoding the catalytic subunit of PI3Kdelta in patients with PASLI/APDS
- Collaborative investigation of targeted PI3Kdelta inhibition as a therapy for PASLI/APDS
- Discovery of novel roles for senescence-related kinases in T cell biology
- Solved disease genes in ongoing studies of patients with undiagnosed inherited immune disorders