Konstantinos Lefkimmiatis, Full Professor, P.I.
Liliana Felicia Iannucci (Assistant Professor)
Mauro Vismara (Postdoc)
Filippo Conca (PhD student)
Doruk Kaan Bayburtlu (PhD student)
Alessandra Tavoni (PhD student)
Our focus is the identification of the signals that allow the functional coordination of cellular organelles, with particular attention to the crosstalk between nucleus and mitochondria.
Ongoing projects:
1. Identification of the molecular mechanisms that regulate the cAMP and Ca2+ pathways in the nucleus during ageing.
While it is well known that during ageing, the balance between kinase and phosphatase in the nucleus is altered, the molecular mechanisms underlying this phenomenon are not well defined. We are developing novel Fluorescence Resonance Energy Transfer (FRET)-based sensors in order to study the molecular determinants of the nuclear cAMP and Ca2+ pathways. Using the ageing skeletal muscle as a model we are studying how phosphatases regulate nuclear kinases during this process.
2. Study the role of nuclear EPAC1 condensates in the pathophysiology of cancer Recent data suggest that PKA in not the only nuclear cAMP effector.
In fact, we recently discovered that another cAMP-activated protein, EPAC1, is present in the nucleus where it regulates the transcription through the generation of nuclear condensates. Currently, we are studying the biophysical mechanisms that determine the formation of nuclear EPAC1 condensates and the role of these structures in the pathophysiology of haematological and ovarian tumours.
3. Studying the communication between nucleus and mitochondria. Identifying the signalling events that govern the functional coordination between nucleus and mitochondria remains a major challenge.
Our laboratory, in collaboration with the Stadler (university of Aarhus) and Daskalakis laboratories (Harvard), is developing matrices capable of simultaneously hosting mitochondria, nuclei and molecular sensors. Thanks to this approach we are studying the signals that the two organelles exchange in real time, while single nuclei RNA sequencing is allowing us to couple the distinct signals exchanged among the two organelles to specific transcriptional signatures.