Professor Manuela Zaccolo

Tiny Signals, Big Impact: Targeting cAMP Nanodomains for Precision Therapy

Abstract:
Cyclic AMP (cAMP) regulates a vast range of physiological processes yet generates highly specific cellular responses. This specificity is achieved through spatial compartmentation of cAMP signalling into discrete nanodomains, where phosphodiesterases, kinases, scaffolds and other regulatory components shape local signals. Disruption of this organisation is increasingly recognised as a feature of disease, including heart failure, where selective remodelling of individual nanodomains can impair cardiac function. In this lecture, I will discuss how defining the molecular architecture of cAMP nanodomains is revealing new mechanisms that regulate cardiac physiology and become altered in disease. Recent work from our laboratory illustrates how individual signalling compartments can be selectively manipulated without perturbing global cAMP signalling. I will also discuss how these insights open opportunities for subcellular precision pharmacology: targeting dysfunctional nanodomains rather than entire signalling pathways to achieve more selective and effective therapeutic interventions

Biography:
Manuela Zaccolo is Professor of Cell Biology at the University of Oxford, where she is Deputy Head of the Department of Physiology, Anatomy and Genetics, Director of the Burdon Sanderson Cardiac Sciences Centre and Director of the Centre for Integrative Physiology. Her research focuses on the molecular mechanisms that confer specificity to intracellular signalling, with particular emphasis on compartmentalised cyclic nucleotide signalling in the cardiovascular system, and on how disruption of these mechanisms contributes to disease.

Association: Manuela Zaccolo — University of Oxford, Medical Sciences Division

Host: Dr Anna Zoccarato