Corrado Spadafora

Corrado Spadafora

Istituto Superiore di Sanità (Italian National Institute of Health); Rome, Italy

Corrado Spadafora's laboratory originally discovered that mature sperm cells from a variety of species share the ability to spontaneously take up exogenous DNA molecules and deliver them to oocytes at fertilization: they called that phenomenon cell-mediated sperm-mediated gene transfer (SMGT). That feature was subsequently exploited, in theirs and other laboratories, to generate genetically modified animals in different species.

SUMMARY OF SCIENTIFIC INTERESTS/ RESEARCH ACTIVITY

In the last twenty years, his research has focussed on the following lines:

a) studies of  sperm cells as vectors of exogenous nucleic acids and the ensuing discovery of sperm-mediated gene transfer (SMGT) as a means of transmission of new genetic information from  males to their progeny;

b) role of Reverse Transcriptase (RT) encoded by LINE-1 retrotransposable elements in SMGT and in the genesis and propagation of new genetic information;

c) characterization of an RT-dependent mechanism, active in early embryogenesis and erroneously reactivated in tumorigenesis;

d) role of  RT as a therapeutic target in cancer.

Profile continued

Spadafora's laboratory originally discovered that mature sperm cells from a variety of species share the spontaneous ability to take up exogenous DNA molecules and deliver them to oocytes at fertilization: they called that phenomenon cell-mediated sperm-mediated gene transfer (SMGT). That feature was subsequently exploited, in their and other laboratories, to generate genetically modified animals in different species). They also found that sperm cells can also take up exogenous RNA molecules and transmit RNA-encoded genetic  information in a process called reverse sperm-mediated gene transfer (SMRGT).

In further efforts to characterize the basic biological and molecular features underlying SMGT, they have identified a complex network of factors that are normally silent in spermatozoa, yet are activated soon after fertilization and contribute to early development. Among those, they have identified an endogenous reverse transcriptase RT activity (5, 6), they we have shown to play a central role in RSMGT and to be involved in the genesis and propagation of new genetic traits, besides those encoded by chromosomal genes and inheritable in a non-mendelian fashion. 

"Our recent studies indicate that the relevant RT activity in this mode of genetic transmission originates from LINE-1 transposable elements and that it is indispensable in early murine embryonic development" says Spadafora.

In developments of these studies we found that the RT activity also plays key roles in cell transformation and cancer progression: indeed, both RT inhibition, and LINE-1 silencing, consistently inhibit cancer cell proliferation and promote their differentiation. These findings have formed the basis for the design of clinical trials using RT inhibitors in a novel differentiating cancer therapy (ongoing trials). Our current efforts are focussing on in-depth studies of RT-mediated molecular mechanisms implicated in normal development and in tumorigenesis.

Quote

 

""Such diverse biological processes as embryonic development, tumorigenesis and evolutionary changes all originate from one same genomic dynamic mechanism, activated at fertilization and dependent on reverse transcriptase encoded by mobile genetic elements. The unscheduled activation of this mechanism outside of the embryonic developmental window, i.e. in differentiated cells, generates cancer, which can therefore be viewed as the price that individuals pay to species evolution.”"

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