User:Alejandro Colaneri

I received my degree in Clinical Biochemistry in Argentina from the National University of Rosario and my PhD in Molecular Biology from the University of Buenos Aires, The main topic of my PhD was the transcriptional network involved in the nuclear-mitochondrial crosstalk, using the plant Arabidopsis thaliana as a model. I traveled to the US to work as a postdoctoral fellow in the laboratory of Dr. Lutz Birnbaumer at NIEHS, who was beginning studies on the imprinting of the GNAS locus. Once in the lab I proposed a new line of work that consisted in the generation of detailed functional maps of DNA methylation patterns in different mammalian cells and tissues, under normal and disease-associated conditions. I designed and developed my own method to profile changes in methylation at genome wide scale. My work was the basis for the NIH Director Challenge Award application in January 2008. This proposal was granted in May 2008 at $450,000. The quality of my research was recognized and awarded by NIH in the FARE (Fellows Awards for Research Excellence) competition in 2010.

My first goal was to create a tool to identify genomic sequences that can be targets of epigenetic mechanisms as a result of environmental influences. The differentially methylated states of these sequences could function as epialleles that might influence complex phenotypes and diseases. That goal was successfully reached and the manuscript is being reviewed previous communication to PNAS with the proof of principal for the method. In this paper I present a detailed description of the methodology and the quantitative analysis pipeline as well as examples showing how the method can identify changes at the level of a single CpG. A second manuscript showing a comparison in the methylome for four different tissues (liver, brain, kidney and testis) is in preparation. At present I am evaluating the impact of the diet (in a proved model for environmental exposition) in the liver mouse methylome. For that purpose we fed animals with diets high or poor in methyl donating nutrients and compare the result against animals fed with a control diet. We pushed the metabolism toward hypo-methylation or hyper-methylation by supplementing the diet with bisphenol A or genistein. In addition I’m studying the genome wide methylation in a mouse model of exposure to undernutrition. In this model, underfeed animals in pregnancy produced a reduced availability of nutrients for the embryos during critical periods of development. Possible permanents changes in gene expression (reprogramming) are expected being detected in the pups by measuring differences in their liver methylation profiles.