Gian Luca Ferri

The NEF-Laboratory

Department of Biomedical Science

Tel: 070 6754001

e-mail: ferri@unica.it

Personal webpage: here

Principal areas of expertise: neuro-edocrine system; biomarkers of disease

Research topic: NEURO-ENDOCRINE SYSTEM

Complex networks in the brain, at the brain-hypothalamus-pituitary interface, and in many organs (stomach, intestine, pancreas, adrenal, adipose tissue, etc) cooperate “in real time” to regulate our eating behaviour and preference/s, sense of hunger and satiation, drinking behaviour and thirst, energy balance and resulting adiposity & body weight. In few words: our whole metabolism, with its alterations and their consequence on our overall cardio-vascular and general health.

Our research tackles the structure and organisation of the neuro-endocrine system, novel transmitter and modulatory molecules, their release and actions, response and modulation by feeding, or alteration in experimental models and human disease conditions.

Special attention is dedicated in our lab to a novel multi-functional precursor named VGF (not acronymic) and its end-product peptides and fragments. Such precursor gives raise to a rapidly adapting diversity of VGF peptides in neurons and endocrine cells. Many so far studied VGF peptides have powerful actions: some increase energy consumption / reduce eating, or inhibit / stimulate release of hormones (e.g. vasopressin), associate with neuronal Long Term Potentiation (LTP) and strengthen central synapses, reduce depression, and so on.

Research topic: BIOMARKERS OF DISEASE

The so-called “Biomarkers” are molecules which can be used as indicators of the risk to develope a certain disease, its stage of progression, the efficacy of a therapy given to a patient, or even to identify potentially new targets for novel therapeutic approaches. In some cases, e.g. autoimmune conditions, abnormal auto-antibodies can be both markers of the disease, as well as important actors in the patho-physiology of damage.

The above “VGF”, again, is relevant. Many VGF peptides were found by proteomics in the Cerebro Spinal fluid, with major changes in NeuroDegenerative and other disease conditions. Some may be related to cancer.

In this context, we investigate VGF peptides in patients affected by Parkinson’s, Alzheimer’s and other neurodegenerative diseases, and in related experimental animal models.

Lately, our expertise in developing antibody-based methods has been put at work to set up the assessment of a potential novel Biomarker of cancer, derived from a newly recognised oncogenic isoform of the BTK protein.

Technology: ADVANCED IMMUNE METHODS

We have wide experience in the production and use of novel antibodies: from selection of antigen molecule and conjugation, to advanced purification and molecular characterisation.

Over the years, we have set-up many novel, ad hoc methods in immunohistochemistry (including novel multi-channel fluorescence, developed with Chroma: www.chroma.com), immunochemistry (ELISA) and related approaches, interfaced with proteomic analyses (ongoing cooperation with Biochemistry labs at our University).

We are tackling parallel sandwich ELISA assays, with an eye to innovative “Antibody Arrays” or similar approaches to measure the multiplicity of cleaved, or otherwise post-translationally modified products derived from one and the same gene (primarily VGF and its derived, diversely bioactive peptides, fragments, molecular forms and biomarkers).

Some of our present RESEARCH LINES:

Neuro-endocrine systems: changes in experimental models of altered feeding, metabolic imbalance, stress conditions
VGF peptides in experimental and human diabetes: tissue changes, actions, possible role/s and significance for patients’ monitoring
VGF peptides in neurodegenerative diseases: experimental models, and plasma profiles at various disease stages in patients
Innovative approaches for the investigation of multi-functional precursors and their alternative peptide products
Autoantibodies to neuro-endocrine cells and neurons in autoimmune models and diseases: correlation to endocrine imbalance, brain alterations and clinical course

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Key publications:

Neuro-endocrine systems and Metabolic regulation

D’Amato F, et al. VGF Peptide Profiles in Type 2 Diabetic Patients’ Plasma and in Obese Mice. PLoS One 2015, doi: http://dx.doi.org/10.1371/journal.pone.0142333

Noli B, et al. Photoperiod Regulates vgf-Derived Peptide Processing in Siberian Hamsters. PLoS One 2015, doi: http://dx.doi.org/10.1371/journal.pone.0141193

Saderi N, et al. A role for VGF in the hypothalamic arcuate and paraventricular nuclei in the control of energy homeostasis. Neuroscience 2014, doi: http://dx.doi.org/10.1016/j.neuroscience.2014.01.060

Cocco C, et al. VGF metabolic-related gene: distribution of its derived peptides in mammalian pancreatic islets. J Histochem Cytochem. 2007 Jun;55(6):619-28. http://journals.sagepub.com/doi/pdf/10.1369/jhc.6A7040.2007

Bartolomucci A, et al. TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity. PNAS USA 2006 Sep 26;103(39):14584-9. http://www.pnas.org/content/103/39/14584.long

Adrian TE, et al. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 1985;89:1070-7 — contemporary classic: >500 citations 2005-2016 http://www.sciencedirect.com/science/article/pii/0016508585902112

Biomarkers, else

Brancia C, et al. VGF Protein and Its C-Terminal Derived Peptides in Amyotrophic Lateral Sclerosis: Human and Animal Model Studies. PLoS One 2016, doi: http://dx.doi.org/10.1371/journal.pone.0164689

Grassilli E, et al. A novel oncogenic BTK isoform is overexpressed in colon cancers and required for RAS-mediated transformation. Oncogene 2016, doi: 10.1038/onc.2015.504. http://www.nature.com/onc/journal/v35/n33/full/onc2015504a.html

Cocco C, et al. Distribution of VGF peptides in the human cortex and their selective changes in Parkinson’s and Alzheimer’s diseases. J Anat 2010, doi: 10.1111/j.1469-7580.2010.01309.x. http://onlinelibrary.wiley.com/doi/10.1111/j.1469-7580.2010.01309.x/full

Cocco C, et al. Median eminence dopaminergic nerve terminals: a novel target in autoimmune poly-endocrine syndrome? J Clin Endocrinol Metab 2005, doi: http://dx.doi.org/10.1210/jc.2004-2184

Massa F, et al. The endogenous cannabinoid system protects against colonic inflammation. J Clin Invest. 2004 Apr;113(8):1202-9. http://www.jci.org/articles/view/19465