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Davide Cacchiarelli

Assistant Investigator, TIGEM

Assistant Professor of Molecular Biology, Department of Translational Medicine, University of Naples Federico II, Italy

Armenise/Harvard Laboratory of Integrative Genomics

Integrative genomic approaches to human cell fate reprogramming in development and genetic diseases

The past decade was characterized by unprecedented progress in the field of descriptive genomics, increasing the capacity to finely map regulatory regions and DNA sequence variants, which are responsible for the phenotypic differences among individuals and susceptibility to diseases. Recent findings into control of gene expression programs had an essential impact on our perception of transcriptional misregulation in pathologic conditions, as many different disorders can be due to mutations in regulatory sequences and their cognate transcription factors. Indeed, numerous mendelian diseases are attributable to alterations in transcription factors acting at the node of gene regulatory networks, often responsible for subtle changes in critical moments of cell fate decisions.
Some transcription factors with a dominant role in controlling cell fate decisions are also capable of reprogramming cell states when ectopically expressed, turning somatic cells into stem cells or new cell identities and thus stimulating new research directions into human regenerative medicine. However, the chance to successfully develop patient-tailored therapies is still very limited because reprogramming technologies lack a comprehensive understanding of the molecular processes involved, and manufacturing cells require knowing the exact combination of genes governing the transitions from the starting cell type to the target type. Also, the precise dynamics through which transcription factors regulate cell fate decisions and to what extent associated DNA sequence variants can determine pathogenic effects is still largely unknown.
In our lab, we carry out a multifaceted approach that combines a wide range of genomic strategies to significantly advance our understanding of the regulatory logic driving cell fate during human reprogramming. Our ultimate goal is to improve the quality and fidelity of such strategies to unlock the full potential of induced cell fate reprogramming in regenerative medicine therapies.

Davide Cacchiarelli PhD

Genomic Medicine

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