Eliezer Calo

My research focuses on the molecular entities controlling and coordinating RNA metabolism, the compendium of all processes that involve RNA, such as synthesis, processing, modifications, export, translation and degradation, and their role in development and disease. Our goal is to understand how different aspects of RNA metabolism are coordinately controlled to generate structure and function during development and how mutations in components of the RNA metabolic program lead to congenital disorders and cancer

                     

Figure: Simplified schematic of the RNA metabolic program leading to the assembly of the translational apparatus. Ribosome biosynthesis relies on the coordinate action of all three RNA polymerases to produce the ribosomal RNAs (rRNAs) and each of the 81+ ribosomal proteins. Additionally, the processing and maturation of the rRNAs and the assembly of the ribosomes require an army of nearly 200 proteins. Mutations in ribosomal proteins result in ribosomopathies a collection of childhood disorders resulting in specific clinical phenotypes and predisposition to cancer. (in blue are a subset of known ribosomopathy-associated genes and their normal functions). 


Calo E, Flynn RA, Martin L, Spitale RC, Chang HY, Wysocka J. RNA helicase DDX21 coordinates transcription and ribosomal RNA processing. Nature. 2015 Feb 12;518(7538):249-53. PMCID: PMC4827702.

Calo E, Quintero-Estades JA, Danielian PS, Nedelcu S, Berman SD, Lees JA. Rb regulates fate choice and lineage commitment in vivo. Nature. 2010 Aug 26;466(7310):1110-4. PMCID: PMC2933655.

Flynn RA, Do BT, Rubin AJ, Calo E, Lee B, Kuchelmeister H, Rale M, Chu C, Kool ET, Wysocka J, Khavari PA, Chang HY. 7SK-BAF axis controls pervasive transcription at enhancers. Nat Struct Mol Biol. 2016 Mar;23(3):231-8. PMCID: PMC4982704.

Buecker C, Srinivasan R, Wu Z, Calo E, Acampora D, Faial T, Simeone A, Tan M, Swigut T, Wysocka J. Reorganization of enhancer patterns in transition from naive to primed pluripotency. Cell Stem Cell. 2014 Jun 5;14(6):838-53. PMCID: PMC4491504.

Calo E, Wysocka J. Modification of enhancer chromatin: what, how, and why? Mol Cell. 2013 Mar 7;49(5):825-37. PMCID: PMC3857148.

Hilgendorf KI, Leshchiner ES, Nedelcu S, Maynard MA, Calo E, Ianari A, Walensky LD, Lees JA. The retinoblastoma protein induces apoptosis directly at the mitochondria. Genes Dev. 2013 May 1;27(9):1003-15. PMCID: PMC3656319.

Pritchard CD, O'Shea TM, Siegwart DJ, Calo E, Anderson DG, Reynolds FM, Thomas JA, Slotkin JR, Woodard EJ, Langer R. An injectable thiol-acrylate poly(ethylene glycol) hydrogel for sustained release of methylprednisolone sodium succinate. Biomaterials. 2011 Jan;32(2):587-97. PMCID: PMC4070531.

Ianari A, Natale T, Calo E, Ferretti E, Alesse E, Screpanti I, Haigis K, Gulino A, Lees JA. Proapoptotic function of the retinoblastoma tumor suppressor protein. Cancer Cell. 2009 Mar 3;15(3):184-94. PMCID: PMC2880703.

Berman SD, Calo E, Landman AS, Danielian PS, Miller ES, West JC, Fonhoue BD, Caron A, Bronson R, Bouxsein ML, Mukherjee S, Lees JA. Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11851-6. PMCID: PMC2575280.