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Marisa GARIGLIO: Research interests/Expertises

Research interests

The laboratory of Viral Pathogenesis by Prof. Gariglio has two major research projects in active state:

  1. Understanding the biology of human papillomavirus infection focusing on the immunocompromised host

    Human Papillomaviruses (HPVs) are small DNA tumour viruses that have a circular double stranded DNA genome of ∼8 kb in length, including non-structural early (E) and structural late (L) genes.

    To date, more than 150 HPV types have been completely sequenced, belonging to five genera (α,β,μ,ν and γ) and a series of intragenus species (indicated by Arabic numbers) based on sequence analysis; the different types have different life-cycle characteristics and disease associations. The α genus contains the mucosal genotypes associated with genital cancer (e.g. HPV16 and 18), as well as some skin-tropic genotypes associated with common skin warts (e.g. HPV3, 27 and 28). In contrast, the β-genus HPVs result in asymptomatic cutaneous infections in immunocompetent individuals, while in subjects with impaired immune function, including epidermodysplasia verruciformis (EV) and other primary immunodeficiency disorders, they can cause cutaneous lesions that may become difficult to manage and in some circumstances progress to cancer. The main objective of our study is to clarify the molecular mechanisms underlying HPV-induced skin carcinogenesis through the use of human, animal and cellular models. Human model: characterization of the HPV infection pattern in patients with primary and secondary (namely organ transplant recipients) immunodeficiency: PCR, real time PCR, deep sequencing, tissue staining, and human tumor xenografting in nude mice. Animal model: HPV8-transgenic mice as a model of beta HPV-induced skin carcinogenesis. Cellular model: HPV replication assay in human keratinocytes, grown in monolayer or as organotypic raft culture.

  2. Role of the interferon-inducible IFI16 protein in the development of systemic autoimmune diseases

    The nuclear DNA sensor IFI16 protein has been implicated for its role in inflammasome signaling and as viral DNA sensor and restriction factor to a number of retro/herpes viruses. Recently we have described the occurrence of this protein in the sera of systemic autoimmune patients, while also we have demonstrated the clinical role of anti-IFI16 autoantibodies in autoimmune patients. Our present research is more focused on unraveling the molecular action of extracellular IFI16 protein and its role in inflammation. We are also investigating the activity of this protein as restriction factor for HPV replication.

 

Expertises

  • Organotypic Raft cultures of skin equivalents
  • In vitro model of virus replication (papillomavirus & herpesviruses)
  • Xenografting of human tumours in nude mice
  • Deep sequencing for virome analysis
  • Immunohistochemistry/immunofluorescence and digital scanning of the staining
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