Acosta-Alvear, Diego - University of California, Santa Barbara

个人简介

Dr. Acosta-Alvear earned B.S. and M.S. degrees in Biological Sciences at the Universidad de los Andes, in Bogotá, Colombia. He relocated to the US in 2002. He next earned M.S. and Ph.D. degrees in Cellular and Molecular Biology at the New York University Sackler Institute for Graduate Biomedical Sciences. His doctoral work focused on understanding the transcriptional plasticity of the endoplasmic reticulum stress response known as the “unfolded protein response” (UPR). As a postdoctoral fellow in the laboratory of Dr. Peter Walter at the University of California, San Francisco, he studied the inner workings of UPR and the wiring of the proteostasis network in health and disease. Dr. Acosta-Alvear joined the UCSB faculty in 2016.

研究领域

Cells employ complex mechanisms to maintain homeostasis. If homeostasis cannot be restored, apoptosis is initiated to eliminate injured cells for the benefit of the organism. This dichotomy places these homeostatic mechanisms -collectively known as cellular stress responses- at the core of the survival versus death decision. In disease, abnormal cells can remodel their stress responses to gain a survival advantage or evade apoptosis. Our overarching goal is to understand how these fundamental stress response networks operate in healthy cells so we can understand how they become remodeled in disease. By discerning the molecular principles that govern the wiring and re-wiring of cellular stress responses, we can discover new biomedical concepts and pinpoint potential nodes for therapeutic intervention for several diseases. A major current focus of our lab is to understand how RNAs interface with cellular stress response networks to exert regulatory control. In particular, we are interested in understanding the mechanisms by which cells preserve the integrity of their transcriptome; a task coordinated by RNAs and RNA-protein interactions within a specialized homeostatic network we refer to as the “RNA stress response (RSR)”. We pursue an in depth, network-level, understanding of the RSR. To that end, we use a combination of cutting edge high-throughput approaches that include the genome-wide mapping of RNA-protein interactions in living mammalian cells, and the identification of amplifiers and dampeners of the RSR using CRISPR-based genetic screens. Coupling these techniques to more traditional cell biology and biochemistry methods allows us to dissect the building blocks that make up the RSR network and uncover how they work.

近期论文

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Peschek J*, Acosta-Alvear D*, Walter P. A conformational RNA zipper promotes intron-ejection during non-conventional XBP1 mRNA splicing. 2015. EMBO Rep. 2015 Dec;16(12):1688-98. (*Equal contribution and corresponding authors). PMID: 26483401. Cover-featured article. Acosta-Alvear D*, Cho MY, Wild T, Buchholz TJ, Lerner AG, Simakova O, Hahn J, Korde N, Landgren O, Maric I, Choudhary C, Walter P, Weissman JS, Kampmann M*. Paradoxical resistance of multiple myeloma to proteasome inhibitors by decreased levels of 19S proteasomal subunits. eLife. 2015 Sep 1;4:e08153. (*Equal contribution). PMID: 26327694. Lu M, Lawrence DA, Martsers S, Acosta-Alvear D, Kimmig P, Mendez AS, Paton AW, Paton JC, Walter P, Ashkenazi A. Cell Death. Opposing unfolded-protein-response signals converge on death receptor 5 to control apoptosis. Science. 2014 Jul 4;345(6192):98-101. PMID: 24994655 Behrman S, Acosta-Alvear D*, Walter P. A CHOP-regulated microRNA controls rhodopsin expression. J Cell Biol. 2011 Mar 21;192(6):919-27. PMID: 21402790. (*Corresponding author). Acosta-Alvear D, Zhou Y, Blais A, Tsikitis M, Lents NH, Arias C, Lennon CJ, Kluger Y, Dynlacht BD. XBP1 controls diverse cell type- and condition-specific transcriptional regulatory networks. Mol Cell. 2007 Jul 6;27(1):53-66. PMID: 17612490.