Amir Orian, MD, PhD
Associate Professor of Cell Biology
MD PhD, 2000 - Technion, Israel
Biology of identity and non-oncogenic addiction gene networks in cancer
My laboratory seeks to understand the fundamental mechanisms whereby regulatory gene networks determine gene expression. Specifically, we study genes belonging to the ubiquitin and ubiquitin-like pathways that are critical for maintenance of cellular identity. Notably, deregulation of such genes is associated with aging and cancer.
We focus on two gene networks. The first is the “Identity network”, comprising genes required to maintain the identity of differentiated cells and therefore may serve as a barrier for tumorigenesis as well as cellular reprograming. The second is the “Non-oncogenic addiction network (NOA),” involving genes essential for cancer cells to cope with oncogenic stress. The latter is vital for cancer cell survival, but less critical for non-transformed cells and therefore constituent genes have the potential to serve as targets for molecular cancer therapy.
Our current projects include: (1) characterizing the role of SUMO-Targeted-Ubiquitin Ligase proteins in human cancers; and (2) delineating genes within the ubiquitin and ubiquitin-like pathways that regulate adult gut homeostasis and investigating their role(s) in maintaining enterocyte identity, de-differentiation and epithelial cancers. Towards these aims we employ advanced genetic and genomic tools including Drosophila genetics, functional in vivo screens, genomics, biochemistry and cell biology of mammalian cells, mouse-derived intestinal organoids and patient-derived specimens.
For more information, see: https://www.youtube.com/watch?v=yC53-lREHQg or http://www.technioncancer.co.il
Singer R, Shimshi A, Atias O, Oron E, Segal D, Hirsch JA, Tuller T, Orian A, and Chamovitz DA. 2014. Drosophila COP9 Signalosome Subunit 7 interacts with multiple genomic loci to regulate development. Nuc. Acid. Research 42, 9761-9770.
Abed M, Barry KC, Kenyagin D, Koltun B, Phippen TP, Delrow JJ, Parkhurst SM, and Orian A. 2011. The STUbL protein Degringolade is a negative regulator of hairy-mediated Groucho-dependent repression. EMBO J. 30, 1289-1301.
Barry KC, Abed M, Kenyagin D, Werwie TR, Boiko O, Orian A, and Parkhurst SM. 2011. Degringolade a Drosophila STUbL is required for cellularization, sex determination, and early embryonic patterning. Development 138, 1759-1769.
Homeostasis of Drosophila adult gut.
(A) Wild-type adult gut: small intestinal somatic stem cells (ISC, Red) are intercalated between a well-organized array of fully differentiated enterocytes (Green).
(B) Conditional, gene-specific targeting in fully differentiated enterocytes results in re-programing of the gut, impacts tissue architecture and aberrant differentiation. Note the appearance of large cells expressing a stem cell marker (Red) and reduction in the number of fully differentiated enterocytes (Green).