Terzaghi / Luciano

Terzaghi

Laura Terzaghi graduated in Veterinary Medicine in 2011, University of Milan. She started working in private practice with particular interest in oncology; she completed an internship in oncology at Clinica Veterinaria Nerviano (MI) and thanks to a Leonardo project grant - Vets in Europe VII she trained for a six-month period in a Veterinary Referral Cancer and Critical Care Center (VRCC) in Laindon, Essex (UK). Dealing with clinical oncology, she became more and more interested in cancer laboratory diagnosis and mechanisms of action. From 2014 she started following the activity of the Reproductive and developmental biology laboratory (Redbiolab) at the University of Milan; initially dealing with reproductive biology, she is currently involved in a PhD project investigating the role of Progesterone Receptor Membrane Component 1 (PGRMC1) in cell division in both germ cells (oocytes) undergoing meiosis, and ovarian somatic cells undergoing mitosis, with wide implications in reproductive biology as well as ovarian cancer development.


Luciano

Alberto M. Luciano, biologist, graduated in 1991 at University of Milan. He completed a PhD program in Biotechnology applied to Veterinary Sciences at University of Milan and a Post-Doctorate appointment in Reproductive Physiology at University of Connecticut, School of Medicine, CT, USA. Since 2006 he is Associate Professor of Anatomy and Histology, at the Department of Health, Animal Science and Food Safety, University of Milan. Team leader of the Reproductive and Developmental Biology Laboratory (Redbiolab, www.redbiolab.unimi.it), his research interests focus on the processes that regulate mammalian oocyte growth and development. Specific topics are: chromatin remodeling and epigenetic landscaping during oocyte differentiation; Progesterone Receptor Membrane Component-1 and mammalian infertility; biomedical models for premature ovarian insufficiency and polycystic ovary syndrome.
More details on ongoing projects, active collaborations and recent scientific publications of Redbiolab Group at: http://www.redbiolab.unimi.it


Project
Role of Progesterone Receptor Membrane Component 1 (PGRMC1) in cell division

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Progesterone receptor membrane 1 (PGRMC1) is a conserved vertebrate protein, which is found in several tissues and takes part in numerous biological functions.

Figure 1: Human PGRMC1

PGRMC1 is found not only in normal tissues, but is also overexpressed in many types of cancer (i.e, breast, thyroid, colon, ovary, and lung cancer) in which it is involved in cell division and tumor growth. In addition to the well-characterized association with several organelles’ membranes, there is evidence that PGRMC1 takes part in cell division in both germinal and somatic cells, where it has been found among mitotic spindle proteins. However, the precise molecular mechanism(s) by which PGRMC1 takes part in cell division is not known.

Aim of the PhD project is to deepen our knowledge on the mechanism by which PGRMC1 regulates cell division by assessing the effect of its down- and up- regulation and by identifying proteins that interact with PGRMC1 and finally by testing whether post-translational modification regulates PGRMC1 function during both mitosis and meiosis.

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We will use bovine granulosa cells and human ovarian cancer cell lines as well bovine oocytes. Our hypothesis will be tested by using a multidisciplinary approach in which advanced techniques of cell culture, micromanipulation, siRNA mediated gene silencing, overexpression of wild type and mutated forms of PGRMC1, analysis of protein interactions by In situ proximity ligation assay, live imaging, immunofluorescence and confocal microscopy will be used.

 

Figure 2: Localization of PGRMC1 during bovine oocyte meiosis (from Luciano AM et al, Reproduction 2010; 140:663-672)

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Figure 3: Localization of PGRMC1 during SKOV-3 cell mitosis (from Lodde V and Peluso JJ, Biol Reprod 2011; 84:715–722)

 

Our study will clarify PGRMC1 role at each stage of meiotic and mitotic cell division. This knowledge can be useful in the field of oocyte biology and mammalian infertility and for the long-term goal to possibly develop new cancer therapies or diagnostic tools as PGRMC1 is over expressed and interferes with ovarian tumor growth.