Trizzino Research

Marco Trizzino

Contact

Name: Marco Trizzino, PhD
Position: Assistant Professor, Biochemistry & Molecular Biology

233 S 10th Street
826 BLSB
Philadelphia 19107

Telephone: 215-503-0435

Our lab uses a combination of experimental and computational genomics to 1) investigate the function of chromatin remodelers and transcription factors in neurodevelopment, and 2) to unveil how transposable elements rewire gene regulatory networks in mammals.     

Research Projects

Project 1 – Role of the SWI/SNF subunit ARID1B in neurodevelopment

Project1

Many developmental disorders characterized by growth impairment and intellectual disability are associated with mutations in subunits of the multi-protein SWI/SNF chromatin remodeler complex, which is a master regulator of transcription.   For example, ~90% of the patients affected by Coffin-Siris Syndrome, a congenital disease whose phenotype includes hypoplastic fifth fingers and patterning defects in the craniofacial development, present mutations in subunits of SWI/SNF, the very large majority of them (>70%) being haploinsufficient mutations in ARID1B.  I recently demonstrated that ARID1B, and its paralog ARID1A, are not strictly required for the nucleosome remodeling activity of the SWI/SNF complex, instead they modulate promoter-proximal pausing of RNA Polymerase II (RNAPII), a widespread mechanism that controls the timing of expression of developmental genes. In this context, our lab uses induced Pluripotent Stem Cells, CRISPR and experimental genomics to unveil the function of the ARID1B subunit in neuronal differentiation and craniofacial development.

Project 2 – Mechanisms of gene regulation mediated by human-specific SVA transposons

Transposable Elements (TEs) account for ~50% of the human genome, and several studies have suggested an extensive role for these parasitic elements as a critical source of gene-regulatory novelty in mammals.  In this framework, my laboratory aims at unveiling the mechanisms that TEs adopt to regulate and rewire mammalian gene expression.  In particular, the compelling problem that we aim to solve is how a very recent genomic invasion by young mobile elements (SVAs) has set the ground for human-specific gene expression programs. Among the 5 main TE classes, SINE-VNTR-Alus (SVAs) are the youngest, and include 7 subfamilies being either hominid-specific (SVA-A, -B, -C, and -D) or human-specific (SVA-E, -F, and F1).  Importantly, our work demonstrated that SVAs are a significant source of novel cis-regulatory elements in the human genome, acting as both activators or repressors of host-gene expression in a tissue-specific fashion.  Moreover, our preliminary data show that genes proximal to human-specific SVA insertions are enriched for biological processes associated to brain development, craniofacial morphology, and cognitive behavior.  In this context, we use human and chimpanzee’s iPSCs and comparative genomics to characterize the impact and the role of human-specific SVAs to hippocampal neurogenesis, and to the evolution of human cognitive behavior.