Our interests focus on cardiac arrhythmia
mechanisms and possible therapies as arrhythmia is a well-known
condition that leads to sudden death in the normal and failing
heart. Specifically we applied novel medical and customized
technologies for supporting these aims. Cardiac tissue encounters
modifications that start at nanoscale levels, by altering,
locally, the physiology of the subcellular compartments, inducing
structural/functional remodeling and leading to cardiac
arrhythmia. Ongoing efforts aim to define the full range of
subcellular modifications and the functional consequences thereof.
The laboratory is equipped with the state-or art-technologies for
cardiac electrophysiology and nanophysiology: 3D bioprinters,
scanning probe microscopy, non-linear microscopical imaging, FACS,
high-resolution epicardial array, computer vision technology,
optogenetics, Cardiac Organoids functional investigation,
long-terms EP acquisitions, cell culture facilities.
RESEARCH PROJECTS
AVATHEART:
Assessing the mechanisms of impairment of contraction in
Hypoplasic LEft Heart Failure (2024-2026).
The proposed research project aims to deepen our
understanding of the mechanisms underlying contraction impairment
in Hypoplastic Left Heart Syndrome (HLHS). Through a collaborative
effort with the University of Verona, we intend to pioneer
personalized medicine approaches for HLHS patients by creating
Avatheart, individualized organoids derived from induced
pluripotent stem cells (iPSCs) specific to each patient.
This groundbreaking initiative will involve comprehensive drug
screening and mechanical analysis, facilitated by advanced
artificial intelligence (AI) algorithms, concurrently with the
patients undergoing the three crucial cardiac surgical procedures:
the Norwood, Glenn, and Fontan operations.
We will leverage state-of-the-art technologies, including the LOKI
system, in conjunction with optical mapping and deep learning AI
utilizing network theory to analyze electromechanical signals. By
integrating these cutting-edge methodologies, we aim to elucidate
the intricate interplay between electrical and mechanical aspects
of cardiac function in HLHS, thereby paving the way for novel
therapeutic strategies tailored to individual patient profiles.
Through this multidisciplinary approach, we aspire to not only
advance our understanding of HLHS pathophysiology but also to
revolutionize clinical management by offering personalized
treatment modalities that optimize outcomes and quality of life
for affected individuals."
Dissecting
the role of neurogenic factors in Arrhythmogenic
Cardiomyopathy (PRIN 2022) 2023-2025
The research
project aims to elucidate the intricate interplay between
neurogenic factors and arrhythmogenic cardiomyopathy (ACM),
with a particular focus on understanding the mechanisms
underlying sudden cardiac death (SCD).
Our involvement in this project is dedicated to dissecting the
role of neuro-cardio interaction in ACM and SCD. Specifically,
we will investigate the pathophysiology of sudden death using
cardiac organoids derived from human induced pluripotent stem
cells (iPSCs) carrying mutations in desmoglein and plakophilin
genes, which are associated with ACM. These organoids will
comprise cardiomyocytes, endothelial cells, and sympathetic
nervous system (SNS) neurons, aiming to recapitulate the
complex microenvironment of the heart.
Furthermore, our research will encompass electromechanical
evaluations conducted in knockout (KO) mice models deficient
in the aforementioned tight junction proteins. These
assessments will provide crucial insights into the functional
consequences of these mutations on cardiac electromechanical
properties, thus shedding light on the pathogenesis of ACM and
SCD.
In addition, we will explore therapeutic interventions
targeting neurogenic pathways implicated in ACM and SCD.
Specifically, we plan to utilize nanocarriers to deliver
neuropeptide Y (NPY) agonists, leveraging the combined use of
advanced imaging techniques such as ViKIE and MUX for precise
drug delivery and monitoring of therapeutic outcomes.
Through this comprehensive approach, we aim to advance our
understanding of the neurogenic mechanisms underlying ACM and
SCD, ultimately paving the way for the development of targeted
therapies that can mitigate the risk of sudden cardiac death
in affected individuals.
Novel molecular probes
for 4D sensing of electromechanical activity in cardiac
tissue (PR-4D-EMA) 2021-2024
The proposed
research project is dedicated to the innovative design and
synthesis of electrochromic and mechanochromic fluorophores,
engineered to serve as highly sensitive probes for monitoring
membrane potential and tension dynamics within cells. These
advanced fluorophores will revolutionize our ability to
visualize and quantify cellular electromechanical activities
with unprecedented precision and sensitivity.
To facilitate the investigation of these novel fluorophores,
we will leverage the cutting-edge capabilities of the recently
installed multiphoton microscope at the Department of
Chemistry, Life Sciences, and Environmental Sustainability at
the University of Parma. This state-of-the-art facility offers
unparalleled capabilities for three-dimensional fluorescence
imaging based on multiphoton excitation, enabling deep tissue
imaging up to 2 millimeters with sub-micrometer spatial
resolution.
By harnessing the power of multiphoton microscopy, we will be
able to visualize stained specimens in exquisite detail,
capturing dynamic changes in membrane potential and tension at
the cellular level. This imaging modality not only allows for
high-resolution visualization of cellular structures but also
enables real-time tracking of fluorescence signals over time,
facilitating the analysis of electromechanical coupling
dynamics in a four-dimensional space-time framework.
Moreover, the versatility of multiphoton microscopy will
enable us to probe a wide range of variables, including
electric fields, strain, shear stress, and other mechanical
stimuli, which induce characteristic changes in the emission
spectrum of our fluorophores. By correlating these spectral
shifts with specific cellular events, we will gain
unprecedented insights into the complex interplay between
electrical and mechanical signaling pathways within living
cells.
In summary, this interdisciplinary research endeavor will
leverage the synergistic combination of advanced fluorophore
design and state-of-the-art multiphoton microscopy to unravel
the intricacies of electromechanical coupling in cellular
systems. By pushing the boundaries of imaging technology and
molecular design, we aim to unlock new frontiers in our
understanding of cellular physiology and pave the way for
groundbreaking advancements in biomedical research
YIRG:
Young Research Investigator Grant. Organoids on a Chip for
the investigation of inherited cardiac arrhythmias.
2022-2025. PNR 2021-2027 DM731
The project focuses on establishing four postdoctoral positions
within the thematic scope of the National Research Programme (PNR)
2021-2027, specifically targeting the recapitulation of inherited
diseases in vitro. To achieve this goal, we will utilize human
induced pluripotent stem cells (iPSCs) to generate cardiomyocytes
for constructing organoids suitable for high-throughput functional
and molecular screening, utilizing the LOKI System. Additionally,
a new bioreactor equipped with innovative technologies is
currently in development to further advance the project's
objectives.
This endeavor is made possible through collaboration with the
Departments of Drug Discovery and Development (DIA) and
Cardiovascular Sciences, Vascular and Applied Sciences (SCVSA) at
the University of Parma (UNIPR). The project will specifically
focus on studying arrhythmias through functional analyses and drug
screening, leveraging nanodelivery techniques to investigate
potential therapeutic interventions.
The project offers an opportunity to employ four postdoctoral
researchers from diverse disciplines, each contributing to the
multidisciplinary approach required for comprehensive
investigation in this field.
NanoKos: Increase Research Capacities in Kosovo. Nanoparticles in Environment and Medical Research. EuropeAID BGUE-B2020-22.020102-C1-NEAR DELKOS. 2023-2025.
The EU-funded project is dedicated to investigating inhalable
nanoparticles in both environmental and medical research contexts,
with a primary objective of enhancing research capacities in
Kosovo. As part of this initiative, students and postdoctoral
researchers from the University of Pristina will collaborate with
our laboratory, as well as with teams from King's College and the
University of Milan.
Through this collaborative effort, participants will receive
training and education focused on cardiovascular diseases and
nanotherapies, thereby fostering knowledge exchange and
strengthening collaboration among the involved groups. The project
is scheduled to commence in March 2023, marking the beginning of
an exciting journey toward advancing research capabilities and
addressing critical issues in the field.
Novel Nanomaterials
for cardiovascular nanomedicine: SPOKE 1, Materials for
sustainability and ecological transition. WP4: Advanced
materials and devices for health industry, diagnostics and
therapeutics with a one-Health approach. Source of Funding :
PNRR : Next Generation EU: 2022-2025
The second subproject aims to develop nanoparticles capable of releasing pharmaceutical compounds upon inhalation, targeting both pulmonary and cardiovascular applications, as well as ocular administration. We have a pending patent for the administration procedure of these nanoparticles. This subproject also involves the adoption of 3D bioprinting technology for the development of materials capable of localized release of pharmacological compounds, thereby enhancing precision and efficacy in drug delivery.
Through these subprojects, we aim to advance the field of cardiovascular nanomedicine by leveraging innovative nanomaterials and drug delivery strategies. Our efforts align with the overarching goals of promoting sustainability and ecological transition while addressing critical healthcare challenges with a one-health approach.
PAST
GRANTS
We are developing, in collaboration with the Bio engineer
Department and Mathematical Department at University of Pavia, and
the University of Verona a new method for studying kinematic
evaluation of cardiac contraction (ViKiE) at high spatial and
temporal resolutions. The ViKiE computer vision technology is part
of the new European Project on Personalized Medicine ERAPERMED
that aims to acquire right ventricular performance in patients
during Left ventricular assistant device implantation.
The system works in a different way as compared to the commercial ones: briefly, we are recording, in a contact-less fashion manner, the cardiac beating cycle from a beating syncytium, ranging from a single sarcomere of the cardiomyocyte to the entire heart with a high-speed bright-field camera for 1-5 sec. From the video file, a customized algorithm follows the trajectories of a given location during contraction/relaxation processes and returns Hamiltonian mechanical equations such as force, contraction velocity, kinetic energy and displacement. In clinics, VikiE works in parallel with trans-esophageal ecocardiografy during open-chest cardiac surgery and return, in real-time, prognostics and diagnostic values to the surgeons. LVAD-STRAT
New method for predict arrhythmia in Obstructive sleep Apnea Patients: The project SLEEP@SA 2019-2022
SLEEP@SA is a funded project from BRIC INAIL where our team are entitle to develop an Artificial Intelligence able to predict the worsening of cardiac dysfunction in OSA patients. In details we will acquire from worker (pilots, drivers that have a unbalanced biorhythm) ECG, BP and stress biomarkers. All acquired and analyzed data will feed a machine learning for developing such prediction more information at SLEEPOSAS webiste .
Nanoparticles
and cardiac drug delivery: targeting the disease heart via
respiratory pathway. The Project CUPIDO 2017-2021
This is indeed, the other side of the coin, i.e. developing
nanoparticles able to carry and deliver specific drugs to the
failing heart (such as microRNAs or specific peptides). This is
possible with manipulation of the physicochemical nanoparticle
characteristics. The goal of this subproject, conducted in
collaboration with the Department of Life Science University of
Parma, IRGB-CNR and ISTEC-CNR, joint partners in the European
Project Cupido, is to obtain a deeper understating of the
possibility to use electrically charged nanoparticles (promising
results are obtained with calcium phosphate nanoparticles) for
carrying drugs specifically to the failing heart. more details at:
www.cupidoproject.eu
FUNDING AGENCIES
