Cells perceive their surroundings via a myriad of receptors on their surface which initiate a variety of signaling cascades to be transmitted to the nucleus. En route to the nucleus, these signals are selectively either amplified or attenuated in a spatio-temporally restricted fashion to efficiently drive one cellular process at any given time.
While timely amplification of signals is essential to tide over stress or injury in physiologic conditions (such as promote healing in any epithelial wounds/ulcers), sustained enhancement/amplification of signals (in response to growth factors/agonists) heralds oncogenesis and cancer metastasis.
Similarly, abnormal signal amplification is a key feature during an overzealous inflammatory response during wound healing and can be associated with yet another undesired outcome, i.e., fibrogenesis (cardiac fibrosis after myocardial infarction, all causes of liver cirrhosis, pulmonary and renal fibrosis) thereby distorting normal anatomy and impairing normal functions.
We seek to gain insights into how incoming signals initiated by a variety of cell surface receptors are amplified in an unrestricted fashion to drive key cellular processes (secretion, autophagy, growth, proliferation, migration) in health and disease, and identify novel ‘signal-amplification switches/interfaces’ within these signaling pathways which can also serve as therapeutic targets.