Members

Massimo Castagnaro, Francesco Quaglio, Valentina Elena Giuditta Zappulli, Laura Cavicchioli, Silvia Ferro, Maria Elena Gelain, Sandro Mazzariol

Research topic

Neoplastic diseases of dogs and cats in comparative medicine

The Canine Lymphoma Genomics & Epigenomics Group features research programs joining basic science and clinics to study genetics, transcriptome, and epigenetics in lymphoma in dogs. Research focuses on molecular and genomic determinants of lymphoma predisposition, tumour biology, and therapy response. Lymphoma-specific mutations in canine DLBCL and MZL using high-throughput sequencing approaches have been identified by the group in the last years and investigation to characterize the function and clinical aspect in the dogs of the most highly mutated genes is the goal of the group.

To facilitate this research, the group has established collaboration with dr. Stefano Comazzi of the DIVET, Milan to create a bank of lymphoma samples.

The group specific aims are as follow:

-Application of the brand new transcriptome techniques (RNA-seq) to describe the lesions underlying DLBCL in dog and to identify new potential therapeutic targets

-Identification of epigenetic profiling in canine B-cell lymphoma for therapeutic and prognostic stratification and new therapeutic approaches

-Functional studies on the most prevalent DNA binding domains that recognizes and binds specific target sequences in canine lymphoma

-Testing the most promising monoclonal antibodies for lymphoma and melanoma treatment in collaboration with Prof. Hupp, ECRC, Edinburgh

-Exome Sequencing Analysis in Canine Melanoma to investigate mutations associated to the primary tumor and relapse

-Generation of stabilized cell lines and dog derived tumorgrafts (DDT) from canine DLBCL and PTCL in collaboration with Prof. Piva, BIOTEC, Turin

Mammary cancer is the most frequent cancer in pets and women. The aim of the lab is to study the morphological and phenotypical features of this cancer in dogs and cats to standardize the diagnostic histopathological approach as the gold standard for further analysis as prognosis and therapeutic approach are affected by a precise morphological classification.

International collaboration and worldwide standardization are at the base of this activity.

In particular, the collaboration with prof. Michael Goldschmidt (USA), prof. Laura Pena (Spain) and dr. Roberta Rasotto (UK) are strongly addressed in this direction in order to share cases and build an international network.

Additionally, in order to better understand the mechanisms associated with cancer relapses and metastases and innovative therapies, in vitro and in vivo studies are performed, aiming at the identification of genetic and epigenetic changes associated with cancer stem cells and epithelial to mesenchymal transition.

Further, recently described mechanisms (i.e. extracellular vesicles) of interaction between cancer cells and cancer cells with their microenvironment are addressed as responsible of cancer survival, and as relevant biomarkers and potential therapeutic shuttles. The latter aspect is studied also in collaboration with MGH/Harvard Medical School (Boston).

Canine melanoma: The aim of this research topic is to overcome the relative lack of relevant integrated information on proliferative pathways and metastatic features in canine melanomas. Study perspectives including analysis on proteins expression, DNA mutations, RNA expression and epigenetic changes will potentially help to identify key molecules involved with critical improvement in diagnostic and prognostic evaluations and for the development of specific target therapies.

Better defining melanomas through correlations of point mutations, chromosomal, epigenetic, and expression changes between dog and human melanoma, will be important to future goals for modeling human melanoma and improving canine cancer care.

European Veterinary Renal Pathology Service (EVRPS)

Renal failure is one of the most frequent causes of illness and death in veterinary medicine. The Renal Pathology service reviews hundreds of cases annually, for primary diagnosis and consultation/second opinion. Standard light microscopy, direct immunofluorescence and electron microscopy are performed on virtually all biopsies. Special stains are used as needed to evaluate microorganisms, collagen type (IV) chains, and amyloid types. Approximately 80% of cases are from dogs, and the remainders are from cats. Non-neoplastic portions of nephrectomy and autopsy kidneys also are evaluated. In most cases we provide a 48 hours turnaround time. All urgent or significant diagnoses are immediately relayed by telephone to the referring clinicians. The service is provided under the direction of Prof. Luca Aresu, who has a decade internationally recognized experience in the field of renal pathology and research. He is a member of the World Small Animal Veterinary Association’s Renal Standardization group and he has authored or co-authored multiple publications on the canine renal diseases and book chapters on evaluation of the renal biopsy.

Feline Diabetes. Spontaneous feline diabetes is an endocrine syndrome of the aged cat with epidemiologic and clinical features similar to the human counterpart. Histopathology, immunohistochemistry and distribution of the endocrine cells are studied.

Pathology and clinical pathology of marine mammals. The Marine Strategy Framework Directive (EU Directive 2008/56/CE) underlines the urgent need to define target species and biomarkers to assess marine environment health status. Among all, cetaceans may be considered crucial indicators of the health status of animals living in open sea since they are threatened by the risk of accumulating persistent environmental pollutants within their body tissues as top predators. In marine mammals, these chemical substances often act synergistically with biological agents like Cetacean Morbillivirus (CeMV), Toxoplasma gondii and Brucella spp. Despite the huge number of papers suggesting the existence of a pathogenetic synergism between these agents and a range of immunotoxic environmental pollutants, biomolecular mechanisms and immune dynamics regulating this biological/chemical noxae interaction are far from having been elucidated. Main goal of this research is to define a set of suitable biomarkers and matrices in species that usually strand along the Italian coastlines, as stated by Marine Strategy Framework Directive (MSFD), which identifies the need of biomarkers to assess ecological status of the marine environment and the subsequent impact on human health. Particularly, the aim of the research group is identified how CeMV structure varies depending on the different host species affected and how the host immune system reacts and interacts with this infection. The research could be also useful to understand how this RNA virus is causing outbreaks of disease in odontocetes and mysticetes in the Italian basin.
Moreover, our purpose is also the definition of baseline values for clinical-pathological and immunological parameters in cetaceans, in order to provide new tools to evaluate health status, immunological function and host/pathogen interactions.

Zoo and wildlife pathology .The aim is to identify the main diseases and causes of death of animal species living under human care as well as in to wild environment.In addition, the research could be also useful for the study and characterization of possible transmissible diseases and zoonosis as a support for the parks owners and the legislator.

Diseases of aquatic species: turtles, fishes and invertebrates. The aim of this research is to investigate  the pathology of both wild aquatic animals and animals in breeding farms. Little is known about the diseases of wild species in freshwater and salt water. Thanks to the collaboration with other groups of infectious and parasitic diseases, causes of death of individuals and animal groups, such as stranding, are investigated. Researches on pathology (viral, bacterial, fungal, nutritional and environmental) of fish and aquatic organisms are valuable both from a scientific point of view and from the economic repercussions on fishing and aquaculture.