Dr. Jakub (Kobi) Abramson
The Dr. Celia Zwillenberg-Fridman and Dr. Lutz Zwillenberg
Career Development Chair

Office: Wolfson Building, Room 229
Department of Immunology
Weizmann Institute of Science
Rehovot 76100, Israel
Tel: +972-8-934-2776
Fax: +972-8-934-4141
E-mail: jakub.abramson@weizmann.ac.il


Our lab (est. Jan 2011) is broadly interested in deciphering the molecular and cellular mechanisms that control the establishment of immunologic tolerance to self, and understanding how breakdown of this process results in autoimmunity.

Specifically, we focus on a very unique population of the thymic stroma, called the medullary epithelial cells (MECs). Although these cells are extremely rare, they are absolutely essential for the establishment of immunological tolerance. This is due to their amazing capacity to express (and subsequently present) essentially all body antigens, including those whose expression was originally thought to be restricted only to peripheral organs (e.g. insulin, casein, etc). Hence, this “promiscuous” transcription of peripheral-tissue-antigen (PTA) genes in these unique cells “foreshadows” the self-antigens that T cells would encounter once they reach maturity and are released into the body. Many of these ectopic transcripts are regulated by the product of a single gene, the Autoimmune regulator (Aire), as mice with a mutation at this locus express only a fraction of the PTA repertoire. As a result, these animals develop antibodies and immune infiltrates directed at multiple peripheral tissues, resembling a multiorgan autoimmune disorder characteristic of humans with a mutated AIRE gene, the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED).

We aim at further delineation of the molecular and cellular mechanisms of this very important process. In particular we are interested in the identification of additional factors (e.g. transcriptional regulators, receptors, signaling molecules, etc), which operate in MECs and help them to become fully mature cells expressing Aire and complete PTA gene repertoire. We also study the crosstalk between MECs and the thymic microenvironment.

The lab’s research activities combine the use of classical molecular biology techniques with cellular immunology and work with mouse models. This involves a broad spectrum of technologies and procedures such as: Flow cytometry, generation of gene-targeted mice, siRNAs & lentigenics, histological analysis, FTOCs/RTOCs, cell signaling, microarrays and gene expression analysis, ChIP, mass spectrometry and protein-protein interactions analysis, imaging, immunomodulation.