Intra-cellular signals and therapeutic targets

Highly networked signaling hubs are often associated with disease, but targeting them pharmacologically has largely been unsuccessful in the clinic because of their functional pleiotropy. Motivated by the hypothesis that a dynamic signaling code confers functional specificity, we investigated whether dynamic features may be targeted pharmacologically to achieve therapeutic specificity.

Protein kinases became the pharmaceutical industry’s most important class for drug target over the past decade. More focus on identification of signal transduction cascades in the brain regulated by protein kinases may have a significant impact in the field of Alzheimers’ and Parkinson diseases. Using our structural based analyses of protein complex assembly as well as the advanced cellular imaging tools we are investigating how the human brain give rise to these illnesses. We focus on deepening the understanding of the molecular and cellular aspects that promotes or drive brain dysfunction by collaborating with other researchers in the world to reinforce interdisciplinary thinking. This will ultimately lead to novel therapeutic strategies.

Manning, et al (2002)Science 298:1912

Signal Transduction Pathways as Therapeutic Targets in Cancer Therapy

Cancer is increasingly recognized as “miscommunication” disease, in which inter- and intracellular signals are aberrantly sent and/or received, resulting in the uncontrolled proliferation, survival, and invasiveness of the cancer cell. Indeed, many of the genetic and epigenetic aberrations, which underlie the process of neoplastic transformation and progression, ultimately impinge on the inappropriate activation/inactivation of intracellular signaling pathways. Such signaling cascades usually proceed from the cell surface, where growth factors interact with their specific receptors, to cytoplasmic signaling intermediates, where different signals are integrated and both positive and negative feedback circuitry are in place to ensure signal fidelity and transduction accuracy, to nuclear transcription factors/complexes, which ultimately lead to the transcription/translation of effector genes and proteins involved in specific cellular functions.

Intracellular signals determine the properties of a cell within an organism, and participates in the integration of extracellular cues leading to an appropriate cellular response. Our approach focuses on the dynamic aspects of this integration process. We use this experimental framework to monitor adaptations in physiopathological conditions and analyze the effects of pharmacological compounds.