Our research focuses on developing anti-mycobacterial agents and antibody drug conjugates (ADCs) for immunomodulation.
With the emergence of resistant M. tuberculosisstrains (MDR and XDR), co-infection with HIV, the existence of latent tuberculosis infectious (LTBI) and the extensive treatment regimen, our medicinal chemistry program aims at identifying new anti-TB drugs that target both MDR and XDR strains, that are compatible with ART and kill M. tuberculosisin its different physiological states, including LTBI. In this context, we are developing two classes of anti-mycobacterial compounds: MmpL3 inhibitors and compounds that inhibit tryptophan biosynthesis.
The rapid and robust transcriptional induction of the ELR+CXC class of chemokines is necessary to induce neutrophil chemotaxis, the first line of the mammalian innate immune defense. Many critical proinflammatory genes, such as the chemokines, exhibit accessible promoters and are therefore primed for rapid activation. The promoters of these genes are enriched for histone H3K4 trimethylation (H3K4me3), an active chromatin mark that is catalyzed by the mixed-lineage leukemia (MLL) family of methyltransferases. MLL1 is one of the six MLL histone methyltransferases (HMTs) in mammals. In this context, we are developing a new class of ADCs to deliver compounds that can block MLL1 activity.