Alessandro Gardini, Ph.D.

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Wistar Institute Assistant Professor of Biochemistry and Biophysics
Department: Biochemistry and Biophysics

Contact information
The Wistar Institute
3601 Spruce Street
Philadelphia, PA 19104-4265
Education:
B.S., M.S. (Biotechnology)
University of Bologna Medical School, Italy, 2001.
Ph.D. (Molecular Medicine)
University of Milan, Italy, 2008.
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Description of Research Expertise

The Gardini lab investigates how global transcription is regulated during cell differentiation and oncogenesis using a variety of genomics and biochemistry approaches.

Transcription of coding and noncoding genes by RNA Polymerase II (RNAPII) is regulated at several steps: a) transcription factors and chromatin remodelers determine chromatin accessibility and recruitment of the basal transcription machinery; b) RNAPII processivity is determined by a set of elongation factors such as the PAF, Integrator and Super Elongation complexes; c) distal DNA regulatory elements known as ‘enhancers’ establish chromatin loops with neighboring genes and ultimately control RNAPII recruitment and stimulus-dependent gene activation.

There are three major lines of research in the lab:
1 - Role of enhancer and enhancer-derived noncoding RNAs during normal hematopoiesis and leukemia.
2 - Role of chromatin remodelers in ovarian cancer.
3 - Functional dissection of the Integrator protein complex to characterize its role in a) RNAPII elongation and b) processing of noncoding RNAs.

We integrate genome-wide techniques (such as ChIP-seq, RNA-seq and Global RunOn --GRO-seq-- ) with biochemical purification of transcriptional regulatory complexes to assess their subunit composition and identify novel RNA and protein partners.


Transcriptional Activation Mediated by eRNAs

Transcriptional activation mediated by eRNAs.


A typical enhancer is located distal to its target protein coding locus (I) and depends on p300/CBP to maintain an open chromatin status. Binding of a sequence specific TF (II) recruits the Mediator complex (Med) to the enhancer and engages the RNAPII machinery (III) to initiate transcription on both strands. eRNAs are processed by Integrator (Int) to a mature form and bind to Mediator and Cohesin to help enforce a DNA looping between the enhancer and the distal gene (IV), culminating in activation of the target protein coding gene. (adapted from Gardini et al. FEBS J. 2015)




Selected Publications

Lai F. *, Gardini A.*, Zhang A. and Shiekhattar R: Integrator mediates the biogenesis of enhancer RNAs 2015 Sep 17, 525: 399-403. Nature 525: 399-403, 2015 Notes: (*equal contribution).

Gardini A. and Shiekhattar R. : The many faces of long noncoding RNAs. FEBS Journal 282: 1647-1657, 2015.

Chen F., Woodfin A.R., Gardini A., Rickels R.A., Marshall S.A., Smith E.R., Shiekhattar R. and Shilatifard A. : PAF1, a molecular regulator of promoter-proximal pausing by RNA Polymerase II Cell 143: 46-58, 2015.

Gardini A., Baillat D., Cesaroni M., Deqing H., Marinis JM., Wagner EJ., Lazar MA, Shilatifard A. and Shiekhattar R. : Integrator Regulates Transcriptional Initiation and Pause Release Following Activation Mol Cell 56: 128-39, 2014.

Gardini A., Baillat D., Cesaroni M., Shiekhattar R.: Genome-wide analysis reveals a role for BRCA1 and PALB2 in transcriptional co-activation EMBO J 33: 890-905, 2014.

Baillat D., Gardini A., Cesaroni M., Shiekhattar R.: Requirement for SNAPC1 in transcriptional responsiveness to diverse extracellular signals. Mol Cell Biol 32: 4642-4650 2012.

Gardini A, Cesaroni M, Luzi L, Okumura AJ, Biggs JR, et al. : AML1/ETO Oncoprotein Is Directed to AML1 Binding Regions and Co-Localizes with AML1 and HEB on Its Targets. PLoS Genet 4, November 2008.

Neri S., Gardini A., Facchini A., Olivieri F., Franceschi C., Ravaglia G., Mariani E. : Mismatch repair system and aging: microsatellite instability in peripheral blood cells from differently aged participants. Journal of Gerontology:Biological Sciences 60A(3), 2005.

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Last updated: 05/24/2016
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