Dr. Maria Hatzoglou is seeking post-doctoral fellows with technical expertise in molecular biology and with knowledge of stress-response mechanisms.
(Contact Dr. Hatzoglou)
Dr. Maria Hatzoglou graduated from the University of Thessaloniki in Greece in 1981, majoring in Chemistry. She received her Ph.D. in 1985 from the Department of Biology of the University of Athens, where she studied the structure/function of HnRNPs and mechanisms of RNA splicing. She completed her post-doctoral studies in the Department of Biochemistry at Case Western Reserve University, where she studied the regulation of expression of genes contained in retroviruses after infection of cells in vitro and in vivo.
Dr. Hatzoglou joined the Department of Nutrition Faculty in 1991.
Her honors include a fellowship from the National Hellenic Research Foundation, a Basil O'Connor Research Award from the March of Dimes, a Grant in Aid from the American Heart Association (AHA) and continuous funding from the National Institutes of Health (NIH) since 1993.
My laboratory's major research interest for the last 20 years has been the regulation of gene expression by nutrient availability. My laboratory has produced a large body of work on the regulation of expression of the arginine/lysine amino acid transporter gene, cat-1, an essential gene for postnatal life.
Although in the early 1980's biochemists were fascinated by studies showing that cells have adaptive mechanisms to transport amino acids during the stress of amino acid limitation (called adaptive regulation), the molecular mechanisms of this regulation were hampered by the difficulty of cloning the genes for the amino acid transporters. We published the first paper in 1997, on the molecular mechanism of adaptive regulation of cationic amino acid (arginine and lysine) transport (publication 1). This was the beginning of a journey of discoveries on the regulation of expression of the cationic amino acid transporter gene cat-1, by nutrient availability that were published in 18 papers.
A major finding was the regulation of the cat-1 mRNA translation by amino acid availability via a viral-like mechanism, IRES (internal ribosome entry site), which we showed to be dependent on the stress-induced eIF2a-phosphorylation signaling. We published the first regulated mammalian IRES (publication 2, publication 3). This was also the first mammalian riboswitch (publication 4), similar to metabolite control of gene expression in bacteria (publication 5). We also answered the long lasting question of the biochemists in the '80s, by showing that the regulation of transport of neutral amino acids by amino acid availability occurred via an IRES in the SNAT2 amino acid transporter mRNA (publication 6).
Over the last 5 years, our main interest has been on the molecular mechanisms of the cellular response to diverse stress conditions, including inflammation and diabetes. Cellular stress causes reprogramming of transcription and mRNA translation and depending on the intensity of stress and specific cell type factors, cells can adapt to live under stress or they induce apoptosis.
Because the signaling of eIF2a phosphorylation is the MASTER regulator of most cellular responses to stress, we are interested to identify targets of this signaling that contribute to reprogramming of cells in the stressed state. We recently discovered two important molecular mechanisms that control cell fate during stress:
(i) on the nuclear localization of the pro-apoptotic transcription factor chop during endoplasmic reticulum stress (publication 7) and,
(ii) on the regulation of translation of anti-apoptotic mRNAs via the translocation of splicing factors in the cytoplasm during osmotic stress (publication 8).
We are using tissue culture cells and mouse models to further explore these mechanisms under disease conditions.
1. Hyatt SL, Aulak KS, Malandro M, Kilberg MS, Hatzoglou M. Adaptive regulation of the cationic amino acid transporter (Cat-1) in Fao cells. (1997) J. Biol. Chem. 272: 19951-19957.
2. Fernandez J, Yaman I, Mishra R, Merrick WC, Snider MD, Lamers HW, Hatzoglou M. Internal Ribosome Entry Site-mediated Translation of a Mammalian mRNA Is Regulated by Amino Acid Availability. (2001) J. Biol. Chem. 276: 12285-12291.
3. Fernandez J, Yaman I, Sarnow P, Snider MD, Hatzoglou M. Regulation of internal ribosomal entry site-mediated translation by phosphorylation of the translation initiation factor eIF2α. (2002) J. Biol. Chem. 277: 19198-19205.
4. Yaman I, Fernandez J, Liu H, Caprara M, Komar AA, Koromilas AE, Zhou L, Snider MD, Scheuner D, Kaufman RJ, Hatzoglou M. The zipper model of translational control: A small upstream ORF is the switch that controls structural remodeling of an mRNA leader. (2003) Cell 13: 519-531.
5. Fernandez J, Yaman I, Huang C, Liu H, Lopez AB, Komar AA, Caprara MG, Merrick WC, Snider MD, Kaufman RJ, Lamers WH, Hatzoglou M. Ribosome stalling regulates IRES-mediated translation in eukaryotes, a parallel to prokaryotic attenuation. (2005) Mol. Cell. 17: 405-416.
6. Gaccioli F, Huang CC, Wang C, Bevilacqua E, Franchi-Gazzola R, Gazzola GC, Bussolati O, Snider MD, Hatzoglou, M. Amino acid starvation induces the SNAT2 neutral amino acid transporter by a mechanism that involves eukaryotic initiation factor 2alpha phosphorylation and cap-independent translation. (2006) J. Biol. Chem. 281: 17929-17940.
7. Chiribau CB, Gaccioli F, Huang CC, Yuan CL, Hatzoglou, M. Molecular symbiosis of CHOP and C/EB β isoform LIP contributes to ER stress-induced apoptosis. (2010) Mol. Cell. Biol. 30: 3722-31.
8. Bevilacqua E, Wang X, Majumder M, Gaccioli F, Yuan CL, Wang C, Zhu X, Jordan LE, Scheuner D, Kaufman RJ, Koromilas AE, Snider MD, Holcik M, Hatzoglou M. eIF2alpha phosphorylation tips the balance to apoptosis during osmotic stress. (2010) J. Biol. Chem. 285: 17098-111.
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