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Biochemistry and Molecular Pharmacology

Laboratory of Human Pathology in Model Organisms

Head
Luisa
Diomede
Head of Laboratory
Biochemistry and Molecular Pharmacology
luisa.diomede@marionegri.it
Senior Advisor
No items found.

The Laboratory investigates the molecular mechanisms underlying central and systemic amyloidosis, diseases with heterogeneous and complex symptoms caused by proteins impairment. In particular, we focus our attention on the processes that drive protein aggregation, the resulting effects on cellular processes and the toxicity of these aggregates.

For this purpose, we use several experimental models, including the nematode Caenorhabditis elegans, mammalian cell lines and transgenic mice.

The ultimate goal of our studies is the identification of new molecular targets and the development of innovative therapeutic approaches for these diseases, still without a cure.

RESEARCH AREAS

Generation of new invertebrate animal models for the study of central and systemic amyloidosis

Using C. elegans, a small worm less than 1 mm long, we generate "avatars" reproducing the pathogenetic characteristics of central and peripheral amyloidosis. This is very important for studying the mechanisms underlying diseases, especially for rare pathologies for which no animal models are currently available. C. elegans is closer to humans than one might imagine (it shares about 60% of its genes with humans) and, being an invertebrate animal, it does not pose ethical problems related to animal testing.

Investigation of the mechanisms underlying the toxicity of amyloidogenic proteins

We study the pathogenetic process by which some proteins, physiologically present in our organism, change their conformation and acquire the ability to aggregate thus becoming "amyloidogenic" and toxic. This mechanism is at the basis of numerous well-known amyloidoses, such as Alzheimer's disease, but also of rarer diseases such as gelsoline amyloidosis. Once aggregated, amyloidogenic proteins can be deposited in various tissues in the form of aggregates and cause organ dysfunction, but they can also migrate from one cell to another, transferring their toxic potential and altering cellular protein metabolism and nucleic acids.

Development of new therapeutic strategies for immunoglobulin light chain amyloidosis

C. elegans represents the only animal model available to investigate the cause of this disease. We correlate the degenerative process associated with proteotoxicity induced by immunoglobulin light chains with its expression levels, its state of aggregation as well as the expression of genes that can be actively involved in the different phases of the disease. We thus experiment and develop new effective pharmacological approaches and transfer our observations to the clinic.

Studies on new drugs against Covid-19

Since the beginning of the pandemic, in collaboration with the other laboratories of the Department, we have search for new drugs capable of fighting the SARS-CoV-2 infection. The ability of the different compounds to prevent virus entry into cells is evaluated using pseudo-infection cellular and C. elegans models.

Head Unit
Maddalena
Fratelli
Head of Unit
maddalena.fratelli@marionegri.it
Staff
Andrea
Conz
Researcher
andrea.conz@marionegri.it
Anna
Giabelli
Researcher
anna.giabelli@marionegri.it
Carmina
Natale
Researcher
carmina.natale@marionegri.it
Chiara
Nalin
Researcher
chiara.nalin@marionegri.it
Ilaria
Rossoni
Researcher
ilaria.rossoni@guest.marionegri.it
Margherita
Romeo
Researcher
margherita.romeo@marionegri.it
Maria Monica
Barzago
Researcher
mariamonica.barzago@marionegri.it
Michele
Mosconi
Researcher
michele.mosconi@marionegri.it
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International Consensus on Cardiopulmonary Resuscitation.

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Head
Luisa
Diomede
Head of Laboratory
Biochemistry and Molecular Pharmacology
luisa.diomede@marionegri.it
Senior Advisor
No items found.

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