Dr. Aittaleb received his PhD in Biochemistry from the University of Liege in Belgium. His dissertation was on “molecular and structural adaptations to low temperatures of psychrophilic enzymes”.
As postdoctoral fellow at Florida State University’s Institute of Molecular Biophysics, he solved the crystal structure of tRNA methylation complex and demonstrated how snoRNA assemble into snoRNP to guide specific pre-tRNA methylation.
From 2004 to 2015, Dr. Aittaleb held different positions at the University of Michigan. As Howard Hughes Medical Institute Research Associate, he applied the biomolecular fluorescent complementation (BiFC) approach to investigate histone ubiquitylation and the role of poly-glutamine ataxin-3 in neurodegenerative Ataxia disease. Then, he worked as Senior Research Scientist at the Life Sciences Institute and Department of Pharmacology, where he studied the structure and spatiotemporal dynamics of G-protein regulated RhoGEFs. He then worked, as Research Investigator at Department of Molecular, Cellular and Developmental Biology, on the regulation and trafficking of postsynaptic scaffold proteins at the neuromuscular junction.
In 2015, Dr. Aittaleb moved to University of Cincinnati’s Vontz Institute and Brain Tumor Center as Senior Scientist. He was investigating Drug resistance to EGFR therapy and survival pathways of circulating tumor cells (CTCs) in the blood of glioblastoma metastatic patients.
Brain metastasis is the most common intracranial tumor in adults, and is an indicator of poor prognosis with only 15 months median survival. Approximately 90% of all cancer deaths arise from the metastatic spread of primary tumors. Metastasis is a multistep process including dissociation of cancer cells from primary sites, survival in the vascular system, and proliferation in distant target organs. Understanding the molecular mechanism underlying how malignant cells spread from the primary tumor to distant organs, particularly to the brain, is necessary for the development of new diagnostic and therapeutic strategies to improve the patients’ outcome and ultimately prevent/treat metastasis.
RhoGEFs emerged as key regulators of cell motility and invasion in many types of cancer and several activating mutations of various GEFs were found in glioblastoma patients. Depletion of TrioGEF inhibits glioma cell invasion and its over-expression in high grade gliomas correlated with poor patient’s outcome. In addition the VavGEFs were found to be over-expressed across varying grades of gliomas.
Using a battery of cell based assays and advanced imaging techniques, my goal is to understand how cancer cells acquire survival cell motility and proliferation properties that allow them to escape from the primary tumor and invade a secondary metastatic organ.
My ongoing projects are centered on two main topics:
1-defining the molecular mechanisms by which RhoGEFs control cancer cell motility and invasion.
2-elucidating the survival pathway of circulating tumor cells (CTCs) and their dissemination in the blood stream of metastatic patients.
College of Health and Life Sciences - Hamad Bin Khalifa University
2018 - PresentThe Vontz Institute and Brain Tumor Center, Division of Hematology-Oncology, University of Cincinnati.
2015 - 2017Department of Molecular, Cellular, and developmental Biology, University of Michigan.
2011 - 2015Life Sciences and department of Pharmacology, University of Michigan.
2006 - 2011HHMI and department of Biological Chemistry, University of Michigan.
2004 - 2006Kasha Laboratory and Institute of Molecular Biophysics, Florida State University
2000 - 2004University of Liege, Liege, Belgium.
2000“Genetic Mutations Associated with Lung Cancer Metastasis to the Brain”. Mutagenesis 2018 April 13; 33(2): 137-145
2018“Spatial distribution and molecular dynamics of dystrophin glycoprotein components at the neuromuscular junctions in vivo”. J. Cell Sc. 2017 March 15; 130(10): 1752-59
2017“Failure of lysosome clustering and positioning in the juxtanuclear region in cells deficient in rapsyn”. J. Cell. Sci. 2015 Oct 15; 128(20):3744-56.
2015“A role for the CaM-kinase II related anchoring protein alpha-Kap in maintaining the stability of Nicotinic Acetylcholine Receptor” J. Neurosci. 2012 Apr 11; 32 (15): 5177-85
2012“Constitutive Plasma Membrane Association of p63RhoGEF is mediated by palmitoylation and required for basal activity in cells” J. Biol. Chem. 2011 Sep 30; 286(39): 34448-56
2011“Structure and Function of Heterotrimeric G protein-regulated Rho Guanine Nucleotide Exchange Factors” Mol. Pharmacol. 2010 Feb;77(2):111-25. (Figure 1 from this article has been selected for the cover of this issue).
2010“A Conserved Hydrophobic Surface of the LARG Pleckstrin Homology Domain is Critical for RhoA Activation in Cells”. Cell Signal. 2009 Nov; 21(11):1569-78. (This article has been selected by Faculty of 1000).
2009“Structural and Thermodynamic Evidence for a Stabilizing Role of Nop5p in S-adenosyl-L-methionine Binding to Fibrillarin” J. Biol. Chem. 2004 Oct 1; 79(40): 41822-9
2004“Functional Requirement for Symmetric Assembly of Archaeal Box C/D Small Ribonucleoprotein Particles” J. Mol. Biol. 2003 Oct 17; 333(2): 295-306
2003“Structure and Function of Archaeal Box C/D sRNP Core Proteins”. Nat. Struct. Biol. 2003 Apr; 0(4):256-63 (This article has been previewed in Nat. Struct. Biol. 2003 Apr; 10(4): 237-9)
2003