I am currently a researcher within the Italian National Research Council (CNR), Neuroscience Institute, and I work at the Department of Biomedical Science at the University of Padua. I was previously affiliated with the CNR Institute of Biomedical Technologies (ITB) in Milan. The long-term interest of my work is mitochondrial pathophysiology, in particular the molecular characterization and functioning of the permeability transition pore (PTP), and, more recently, the role mitochondria play in neurodegenerative diseases such as Alzheimer's disease, concerning in particular Ca²⁺ dyshomeostasis, reactive oxidative species (ROS) production and metabolic imbalance.
I graduated from the University of Padua with a BSc Degree in Biology, and from the same University I earned a MSc Degree in Biochemistry and Clinical Chemistry. I spent three years of postgraduate research in Molecular Biology at the Vollum Institute, the Oregon Health & Science University, Portland Oregon. From those years in the Pacific North West, together with a robust training in molecular biology, I gained also a love for outdoor sport activities, and in particular for biking.

I have mainly contributed to the study of the role played by the physical/functional connection between endoplasmic reticulum (ER) and mitochondria in the regulation of key intracellular processes, such as the modulation of cell death and cell bioenergetics. In particular, ER-mitochondria interplay has been investigated in the context of Familial Alzheimer's disease. My research focused on the exploration of the molecular nature and of the relationship between proteins mediating ER-mitochondria tethering. I'm currently interested in the generation of novel tools to study organelle juxtaposition in living cells, as well as to investigate the mechanisms leading to the generation and deciphering of Ca²⁺ microdomains in localized subcellular compartments. In addition, by employing and creating specific genetically-encoded fluorescent probes, I'm investigating the dynamics (particularly within mitochondria) of different metabolites and signalling molecules (Ca²⁺, ATP, pyruvate, lactate, etc.), both in cell physiology and pathology. The final goal of my research activity is to understand whether alterations in these pathways are linked to the onset and progression of human pathologies, as well as to test their potential as possible therapeutic targets or as disease biomarkers.

Over the last years, I have been involved in studying calcium (Ca²⁺) signaling in pathophysiology. My research focused on the development of new tools to explore the mitochondrial functionality, and in particular mitochondrial Ca²⁺ dynamics, in vivo. Therefore, I worked on the improvement of mitochondria-targeted Ca²⁺ probes and the creation of a new mitochondria-targeted Channelrhodopsin. These methodologies are instrumental for addressing with novel approaches the role of second messenger heterogeneity in different pathophysiological conditions not only in cell cultures, but also in tissue preparations (acute slices) and in vivo. Currently, I am interested in studying Familial Alzheimer's Disease (FAD), focusing on the imbalance of cellular Ca²⁺ homeostasis. Indeed, Alzheimer's disease (AD) is the most frequent form of dementia, a small percentage of cases is inherited (FAD), due to dominant mutations in the genes encoding for Amyloid Precursor Protein (APP), Presenilin-1 (PS1) and Presenilin-2 (PS2). PS1 and PS2 are the catalytic core of the γ-secretase complex. Beside the current hypothesis about amyloid and tau hyperphosphorylated, cellular Ca²⁺ alterations have been reported to contribute to the AD pathogenesis, however this topic is still debated in the scientific community. The final goal is the employment of these newly created tools to perform in vivo Ca²⁺ measurements in different tissues and subcellular compartments in animal models of AD.

Diana Pendin is a Researcher at the Neuroscience Institute of the National Research Council since 2018. Her research aims to untangle the molecular basis of the pathogenesis of the neurodegenerative disease Hereditary Spastic Paraplegia (HSP), using Drosophila melanogaster as an animal model. Since the very beginning of her career, she has been particularly interested in understanding how ER morphology alterations affect cellular, and more specifically neuronal, function. Recently, she explored the role of Ca²⁺ homeostasis dysregulation in the development of HSP by employing Ca²⁺ imaging techniques. She also contributed in developing novel tools to study in vivo Ca²⁺ dynamics, including viral vectors and transgenic animals (mice and Drosophila) expressing FRET-based Ca²⁺ probes.

Hi! I am Irene and I recently graduated in Cellular and Molecular Biotechnology. Currently I am a CNR research fellow, my main focus is on the dynamics of interorganelles contacts which I study through chemogenetic reporters.

From '87 to '91, I worked for my Ph.D. under the supervision of T. Pozzan. From '92 to '93, as an EMBO Fellow, I expanded my expertise in electrophysiology at the Max Plank Institut für Biophysikalische Chemie of Göttingen (Germany), under the supervision of R. Penner and M. Hoth. There, I participated in the characterization of the long sought after current responsible for capacitative Ca²⁺ entry (I_CRAC), which they described in '92. In '96, I continued this research in the group directed by B. Nilius in Leuven (Belgium). In '98 I got a permanent position as Assistant Professor at the Dept of Biomedical Sciences (DBS), University of Padua. Here, I continued the characterization of I_CRAC and Ca²⁺ stores in different model cells. In 2000, my interest turned to Ca²⁺ homeostasis in brain cells, under both physiological and pathological conditions. In recent years, I focused on mutant presenilins and their role in Ca²⁺ dysregulation and Alzheimer's disease.

• Selected Publications
  • A. Leparulo , M. Mahmud , E. Scremin, T. Pozzan, S. Vassanelli S, C. Fasolato "Dampened Slow Oscillation Connectivity Anticipates Amyloid Deposition in the PS2APP Mouse Model of Alzheimer's Disease." Cells 2020, 9(1) pii: E54. doi: 10.3390/cells9010054 (2020) 9(1), 54.
  • R. Fontana, M. Agostini, E. Murana, M. Mahmud, E. Scremin, M. Rubega, G. Sparacino, S. Vassanelli and C. Fasolato (2017) "Early hippocampal hyper-excitability in PS2APP mice: role of mutant PS2 and APP" Neurobiology of Aging 50, 64-76.
  • M. Agostini and C. Fasolato (2016) “When, where and how? Focus on neuronal calcium dysfunctions in Alzheimer's Disease” Cell Calcium Nov;60(5):289-298. doi:10.1016/j.ceca.2016.06.008. Review.
  • C. Lazzari, M.J. Kipanyula, M. Agostini, T. Pozzan and C. Fasolato (2015) Aβ42 oligomers selectively disrupt neuronal calcium release. Neurobiology of Aging 36, 877-885.
  • M.J. Kipanyula, L. Contreras, E. Zampese, C. Lazzari, A.K.C. Wong, P. Pizzo, C. Fasolato (corresponding author) and T. Pozzan (2012) Ca²⁺ dysregulation in neurons from transgenic mice expressing mutant presenilin 2. Aging Cell 11, 885–893 ISSN: 1474-9718, doi: 10.1111/j.1474-9726.2012.00858.x.