Constam lab – Developmental and Cancer Cell Biology
A current focus is on live imaging of proprotein convertases and their roles in regulating TGFβ-related activities and other signaling pathways in tumor cells and in their microenvironment. We also study the regulation of mRNA translation and cell metabolism by the RNA-binding protein Bicc1 and specific interacting factors that are mutated in polycystic kidney diseases and other ciliopathies.
Our research projects are grouped in three topics:
TGFβ signaling networks governing stem cell self-renewal and lineage differentiation are frequently co-opted and re-wired by cancer cells to promote tumor progression and metastasis. We investigate how such factors and their bioavailability in the tumor microenvironment are regulated at the level of precursor processing to promote tumor immune evasion and other cancer hallmarks.
Proprotein convertases (PC) comprise a family of nine serine endoproteases that process the precursors of secreted growth factors, hormones, adhesion molecules and matrix metalloprotease. We combine genetic approaches and live imaging of PC activities by compartment-specific biosensors to delineate how specific inhibitors should be delivered to preferentially suppress tumor-promoting PC functions.
Biochemical reactions can be compartmentalized in membrane-less organelles by phase-transitioning of aggregation-prone scaffold proteins. We study the regulation of this process by the self-polymerizing RNA-binding protein BICC1 and its impact on mRNA translation and energy metabolism in polycystic kidney diseases and other ciliopathies.