Principal Investigator

Brian Lawson, PhD

I received both my undergraduate and graduate degrees in Microbiology from Clemson University in South Carolina.  Following this, I undertook post-doctoral training in Immunology at The Scripps Research Institute in La Jolla, California, where I was mentored by Professor Argyrios N. Theofilopoulos, M.D.  After a relatively short foray into industrial reagent production and preclinical research, I returned to Scripps.  Upon returning to Scripps and subsequent promotion to faculty, I managed my lab and directed an international undergraduate summer research program.  This immersive ten-week program attracted talented undergraduates globally.  A substantial component of our summer program was minority outreach, supported by yearly funding from Novartis for additional under-represented minority students in science, over and above those supported by Scripps.  In addition to my responsibilities at Scripps, I held a joint role as a Principal Investigator at both the California Institute of Biomedical Research and The International AIDS Vaccine Initiative (IAVI).  In 2020, I moved to The Scintillon Institute in San Diego to carry on my research work and direct a summer research program, this time for high school students.

My early research papers focused on the role of cytokines, T cells, and cell cycle regulators in systemic autoimmunity.  I successfully developed gene therapeutic approaches for lupus treatment and demonstrated T cells' essential role in lupus pathogenesis.  Later lupus-related studies revealed the critical roles of Coronin-1A and transmethylation reactions in systemic autoimmunity.  I also concentrated on Experimental Autoimmune Encephalomyelitis (EAE), an animal model for the autoimmune disease Multiple Sclerosis.   In this model, I found similarities with lupus, as T cells require methylation reactions for proper activation, and inhibiting this process is beneficial.  In separate studies, we performed an image based in vitro high-throughput small molecule screen.  Repurposing drugs identified in the screen, we were able to break the maturation block of resident oligodendrocyte precursor cells, pushing them to mature to fully remyelinating oligodendrocytes, thus reversing established EAE.  We also identified that by blocking IL-7R, we could treat and reverse established EAE.  Throughout my career, I have actively collaborated with various teams, predominantly within the realm of autoimmune diseases.  Our team has demonstrated the essential role of terminal deoxynucleotidyl transferase in lupus development (in collaboration with the Feeney group).  We've also shown that donor thymic dendritic cells, but not splenic ones, can prolong graft survival in recipient mice by educating naïve, newly emerging host T cells (Duncan group).  Further, post-translational modifications like isoaspartylation likely have significant roles in lupus development (Mamula group).  Our research revealed that blocking IL-7R successfully treated lupus-prone animals, similar to our work in the EAE model.  We also showed that nucleic acid sensing TLRs are necessary for the varied anti-nuclear antibodies seen in lupus (Theofilopoulos and Kono groups).  In a collaborative study with Nobel Laureate Dr.  Bruce Beutler, we reported that SHP-1 ENU mutants exhibited a chronic inflammatory phenotype driven by enhanced microbe-activated TLR signaling.  Reapplying ENU mutagenesis with Dr.  Beutler, we showed a beneficial effect of an Unc93b mutation in lupus mouse models.  Furthermore, Slfn2 ENU mutants demonstrated increased susceptibility to bacterial and viral infections due to reduced T cell numbers failing to proliferate upon antigenic challenge.  We have made several significant findings in cancer-related studies with Peter Schultz's group.  These include the development of a novel small-molecule/bispecific antibody conjugate for prostate cancer treatment and confirmation that CLL-1 is a valid target for Acute Myeloid Leukemia via bispecific antibody administration.  We have created two anti-CXCR4-drug conjugates using unnatural amino acid technology, which were successful in eliminating pulmonary lesions in a lung-seeding tumor mouse model and treating xenograft rodent models of multiple myeloma with bispecific and CAR T cell therapies targeting BCMA or CS-1.  We've also evaluated structurally diverse bispecific antibodies, assessing their valency and the necessity of an Fc domain in their structures for treating breast cancers with low or heterogeneous Her2 expression.  In our most recent work with the Nemazee group at Scripps, we discovered that mice deficient in either PLD3 or PLD4 developed severe liver inflammation due to exaggerated responses to TLR9 engagement.  This finding underlines the importance of these enzymes in regulating inflammatory cytokine responses via the degradation of nucleic acids.

More recently, I have ventured into a new research area focused on lentiviral-mediated CAR T cell immunotherapeutic approaches for HIV treatment.  Initially funded by amfAR, this project led to an NIH R21 and a full R01.  We are also supported by CIRM to extend these studies to hematopoietic stem cells, where we aim to target and destroy virus-producing host cells using scFVs derived from anti-HIV broadly neutralizing antibodies.