Davide Cacchiarelli

Biography Research Interests Research Group Publications

Associate Investigator

Other positions:
"Rita-Levi Montalcini" Associate Professor of Molecular Biology - Department of Translational Medicine, University of Naples "Federico II"
"Armenise-Harvard" Principal Investigator of the Laboratory of Integrative Genomics

Davide Cacchiarelli obtained a Master’s Degree and a Doctorate Degree in Genetics and Molecular Biology from University of Rome “La Sapienza”, working on mechanisms of RNA regulation. In 2011, he moved to The Broad Institute of MIT and Harvard and The Department of Stem Cell and Regenerative Biology at Harvard University to focus his research on the rules governing cell fate transitions and reprogramming using genomic approaches. He returned to Italy in 2017 thanks to the Armenise Harvard Foundation Career Development Award and now he leads the Laboratory of Integrative Genomics at TIGEM and coordinates a research group focused on understanding the dynamics of cell fate decisions, funded by an ERC-StG. Davide Cacchiarelli is an experienced genomics leader with a demonstrated history of working in academia and industry. He has made important contributions to the field of descriptive, functional and clinical genomics, epigenomics, and miRNA function. Cacchiarelli’s research leverages an interdisciplinary approach that brings together pluripotency and stem cell biology with cellular engineering, molecular diagnostics, genomic approaches and mathematical modeling.

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

We are a computational and functional genomics laboratory focused on understanding how gene regulation determines cellular identity and how its disruption causes genetic diseases. By combining innovative experimental techniques with advanced computational models, we greatly improve our ability to precisely map regulatory regions and DNA sequence variants. These variants contribute to individual phenotypic differences and disease risk.

Key Research Areas

Interpreting Genetic Variation (VUS)

Moving beyond descriptive catalogs, we emphasize the functional and diagnostic analysis of Variants of Unknown Significance (VUS). Our aim is to provide direct insights for patient care through:

Large-scale targeted sequencing of real-world cohorts.
Diagnostic RNA sequencing to identify splicing issues.
High-throughput saturation mutagenesis for systematic evaluation of variant impacts in key genomic areas.

Computational Genomics and Multi-Omics

Our dedicated computational team specializes in the integrative analysis of large-scale datasets to understand chromatin accessibility and transcription factor dynamics. We utilize:

Single-cell technologies: scRNA-seq, scATAC-seq, and multiomics approaches.
Advanced modeling: Machine learning, regulatory network inference, and combined epigenomic-transcriptomic methods.

Cell Fate decision and reprogramming

We analyze how Transcription Factors (TFs) coordinate cell fate decisions.

Master Regulators: We examine how TFs define and sustain cell identity.
Perturbation Assays: We employ combinatorial TF perturbation and spatial transcriptomics to decipher regulatory logic.
Translational Goal: Our aim is to overcome challenges in cellular reprogramming to create safe and effective clinical therapies.

Our Impact

From deciphering Mendelian disorders to advancing regenerative medicine, our scientific program is designed to translate fundamental genomic insights into robust clinical solutions. We are redefining how transcriptional misregulation is understood in pathology.

Genomics Medicine

Antonio Grimaldi

Postdoctoral Fellow