TRANSAUTOPHAGY European Network for Multidisciplinary Research on Autophagy
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Curriculum Vitae
CURRICULUM VITAE Name : Prof. Devrim GOZUACIK, MD PhD Address : Koç University, School of Medicine, KUTTAM Research Center for Translational Medicine, Topkapi 34010, Istanbul, TURKEY. Phone : +90 212 467 87 00 E-mail : [email protected] Orcid ID : https://orcid.org/0000-0001-7739-2346 EDUCATION 2001, Ph.D. of Molecular Cell Biology, Paris Pasteur Institute and Paris-Sud (XI) University. 1997, M.Sc. (French D.E.A. degree) of Biochemistry, Ecole Polytechnique and Paris-Sud University. 1995, Medical doctor (MD) degree, Hacettepe University, Faculty of Medicine (in English). 1994, Research fellow, Dept. of Tumor Biology, Rotterdam Erasmus Medical Center. 1989-1995, Student researcher, Hacettepe Children’s Hospital Medical Biology Dept. and Hacettepe Oncology Institute. EMPLOYMENT June 2020-today, Professor, School of Medicine, KUTTAM Research Center for Translational Medicine, Koç University. 2018-today, Affiliate Member, Autophagy, Inflammation and Metabolism (AIM) Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, USA. 2018-today, Part-Time Senior Researcher, SUNUM Nanotechnology Research and Application Center. 2016-2020, Co-Founder and Board Member, EFSUN Nanodiagnostics Center of Excellence. 2018-2020, Professor, Molecular Biology Genetics and Bioengineering Program, Sabanci University. 2011-2018, Associate Professor, Molecular Biology Genetics and Bioengineering Program, Sabanci University. Sept. 2006-2011, Assistant Professor, Biological Sciences and Bioengineering Program, Sabanci University. 2001-2006, Postdoctoral fellow, Weizmann Institute of Science (Adi Kimchi Lab). CITATIONS AND H-INDEX 8338 citations in the Science Citation Index (SCI, Thomson-Reuters), h-index: 25. 8710 citations in Scopus, h-index: 25 13670 citations in Google Scholar, h-index: 28. 11 publications with >100 citations. -
ATG9A Protects the Plasma Membrane from Programmed and Incidental Permeabilization
ARTICLES https://doi.org/10.1038/s41556-021-00706-w ATG9A protects the plasma membrane from programmed and incidental permeabilization Aurore Claude-Taupin 1,2, Jingyue Jia1,2, Zambarlal Bhujabal3, Meriem Garfa-Traoré4, Suresh Kumar1,2, Gustavo Peixoto Duarte da Silva 1,2,5, Ruheena Javed1,2, Yuexi Gu1,2, Lee Allers1,2, Ryan Peters1,2, Fulong Wang1,2, Luciana Jesus da Costa5, Sandeep Pallikkuth6, Keith A. Lidke 6, Mario Mauthe7, Pauline Verlhac7, Yasuo Uchiyama8, Michelle Salemi9, Brett Phinney 9, Sharon A. Tooze 10, Muriel C. Mari7, Terje Johansen 3, Fulvio Reggiori 7 and Vojo Deretic 1,2 ✉ The integral membrane protein ATG9A plays a key role in autophagy. It displays a broad intracellular distribution and is present in numerous compartments, including the plasma membrane (PM). The reasons for the distribution of ATG9A to the PM and its role at the PM are not understood. Here, we show that ATG9A organizes, in concert with IQGAP1, components of the ESCRT system and uncover cooperation between ATG9A, IQGAP1 and ESCRTs in protection from PM damage. ESCRTs and ATG9A phenocopied each other in protection against PM injury. ATG9A knockouts sensitized the PM to permeabilization by a broad spectrum of microbial and endogenous agents, including gasdermin, MLKL and the MLKL-like action of coronavirus ORF3a. Thus, ATG9A engages IQGAP1 and the ESCRT system to maintain PM integrity. he autophagy1,2 and ESCRT systems3–5 both act in the remodel- is present in numerous intracellular compartments, including the ling of cellular membranes and contribute to a range of intra- trans-Golgi network and early and recycling endosomes21,22, and traf- cellular homeostatic functions and biological processes. -
CV Abhinav-Diwan.Pdf
CURRICULUM VITAE Abhinav Diwan, MBBS, FACC, FAHA Date: 12-22-2020 Address and Telephone Numbers Lab Website: www.diwanlab.com Office: 827 CSRB-NTA, Center for Cardiovascular Research St. Louis, MO 63110; Tel: 314-747-3457; Fax: 314-362-0186 Present Position: 5/15/2008-present: Staff Physician, Internal Medicine Service, VAMC, St. Louis, MO (5/8th appointment). 1/1/2019-present: Associate Division Chief for Research and Academic Affairs, John Cochran VA medical center 7/1/2020-present: Professor of Medicine (with tenure), Cardiovascular Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 7/1/2020-present: Professor of Cell Biology and Physiology (Secondary appointment), Washington University School of Medicine, St. Louis, MO 7/1/2020-present: Professor of Obstetrics and Gynecology (Secondary appointment), Washington University School of Medicine, St. Louis, MO Education: Undergraduate: Delhi Public School Bhilai, CG, India Graduate and Postgraduate: 01/1991-02/1997: M.B.B.S. (Bachelor of Medicine, Bachelor of Surgery), All India Institute of Medical Sciences, New Delhi, India 07/1997-07/1998: Internship in Internal Medicine, Baylor College of Medicine, Houston, TX 07/1998-07/2001: Residency in Internal Medicine (Medical Resident Investigator Track under the PSTP pathway), Baylor College of Medicine, Houston, TX 07/2001-07/2004: Fellowship in Cardiovascular Science, Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX Medical Licensure and Board Certification: -
Ambroxol and Ciprofloxacin Show Activity Against SARS-Cov2 in Vero E6 Cells at Clinically- Relevant Concentrations
bioRxiv preprint doi: https://doi.org/10.1101/2020.08.11.245100; this version posted August 11, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Ambroxol and Ciprofloxacin Show Activity Against SARS-CoV2 in Vero E6 Cells at Clinically- Relevant Concentrations Steven B Bradfute,1 Chunyan Ye,1 Elizabeth C Clarke,1 Suresh Kumar,2,3 Graham S Timmins,2,4 and Vojo Deretic.2,3 1 Center for Global Health, Department of Internal Medicine, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA 2 Autophagy, Inflammation and Metabolism (AIM) Center, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA 3 Department of Microbiology and Molecular Genetics, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA 4 Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA Abstract. We studied the activity of a range of weakly basic and moderately lipophilic drugs against SARS CoV2 in Vero E6 cells, using Vero E6 survival, qPCR of viral genome and plaque forming assays. No clear relationship between their weakly basic and hydrophobic nature upon their activity was observed. However, the approved drugs ambroxol and ciprofloxacin showed potent activity at concentrations that are clinically relevant and within their known safety profiles, and so may provide potentially useful agents for preclinical and clinical studies in COVID-19. -
Autophagy and Macrophage Functions: Inflammatory Response and Phagocytosis
cells Review Autophagy and Macrophage Functions: Inflammatory Response and Phagocytosis Ming-Yue Wu and Jia-Hong Lu * State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China; [email protected] * Correspondence: [email protected]; Tel.: +853-8822-4508 Received: 25 November 2019; Accepted: 20 December 2019; Published: 27 December 2019 Abstract: Autophagy is a conserved bulk degradation and recycling process that plays important roles in multiple biological functions, including inflammatory responses. As an important component of the innate immune system, macrophages are involved in defending cells from invading pathogens, clearing cellular debris, and regulating inflammatory responses. During the past two decades, accumulated evidence has revealed the intrinsic connection between autophagy and macrophage function. This review focuses on the role of autophagy, both as nonselective and selective forms, in the regulation of the inflammatory and phagocytotic functions of macrophages. Specifically, the roles of autophagy in pattern recognition, cytokine release, inflammasome activation, macrophage polarization, LC3-associated phagocytosis, and xenophagy are comprehensively reviewed. The roles of autophagy receptors in the macrophage function regulation are also summarized. Finally, the obstacles and remaining questions regarding the molecular regulation mechanisms, disease association, and therapeutic applications are discussed. Keywords: macrophage; autophagy; inflammatory response; phagocytosis 1. Introduction Autophagy is a highly conserved mechanism by which the cytoplasmic cargo is delivered to the lysosomes for degradation. There are at least three forms of autophagy: chaperone-mediated autophagy (CMA), microautophagy, and macroautophagy. Macroautophagy is the major autophagic degradation form that maintains the cell homeostasis and organelle quality control in eukaryotic cells. -
Atg8ylation As a General Membrane Stress and Remodeling Response
Review www.cell-stress.com Atg8ylation as a general membrane stress and remodeling response Suresh Kumar1,2, Jingyue Jia1,2 and Vojo Deretic1,2,* 1 Autophagy Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. 2 Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA. * Corresponding Author: Vojo Deretic, Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; E-mail: [email protected] ABSTRACT The yeast Atg8 protein and its paralogs in mammals, mammalian Atg8s (mAtg8s), have been primarily appreciated for Received originally: 29.05.2021 their participation in autophagy. However, lipidated mAtg8s, in revised form: 26.07.2021, including the most frequently used autophagosomal membrane Accepted 30.07.2021, Published 12.08.2021. marker LC3B, are found on cellular membranes other than au- tophagosomes. Here we put forward a hypothesis that the lipi- dation of mAtg8s, termed ‘Atg8ylation’, is a general membrane Keywords: ubiquitylation, endosome, exosomes, stress and remodeling response analogous to the role that ubiq- microvesicles, secretory autophagy, unconventional uitylation plays in tagging proteins. Ubiquitin and mAtg8s are secretion, secretion, ubiquitin, galectin, lap, lc3, atg8, related in sequence and structure, and the lipidation of mAtg8s tfeb, lysosome, ampk, mtor, autophagy. occurs on its C-terminal glycine, akin to the C-terminal glycine of ubiquitin. Conceptually, we propose that Abbreviatons: mAtg8s and Atg8ylation are to membranes what ubiquitin and AIM – Atg8-interacting motif; EV – extracellular ubiquitylation are to proteins, and that, like ubiquitylation, vesicle; ILV – intralumenal vesicle; LANDO – LC3- Atg8ylation has a multitude of downstream effector outputs, associated endocytosis; LAP – LC3-associated phagocytosis; LIR – LC3 interacting region; mAtg8s – one of which is autophagy. -
Interleukin-10 Deficiency Exacerbates Inflammation-Induced Tau Pathology Lea L
Weston et al. Journal of Neuroinflammation (2021) 18:161 https://doi.org/10.1186/s12974-021-02211-1 RESEARCH Open Access Interleukin-10 deficiency exacerbates inflammation-induced tau pathology Lea L. Weston1, Shanya Jiang1, Devon Chisholm1, Lauren L. Jantzie2 and Kiran Bhaskar1,3* Abstract Background: The presence of hyperphosphorylated microtubule-associated protein tau is strongly correlated with cognitive decline and neuroinflammation in Alzheimer’s disease and related tauopathies.However,theroleof inflammation and anti-inflammatory interventions in tauopathies is unclear. Our goal was to determine if removing anti- inflammatory interleukin-10 (IL-10) during an acute inflammatory challenge has any effect on neuronal tau pathology. Methods: We induce systemic inflammation in Il10-deficient (Il10−/−)versusIl10+/+ (Non-Tg) control mice using a single intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) to examine microglial activation and abnormal hyperphosphorylation of endogenous mouse tau protein. Tau phosphorylation was quantified by Western blotting and immunohistochemistry. Microglial morphology was quantified by skeleton analysis. Cytokine expression was determined by multiplex electro chemiluminescent immunoassay (MECI) from Meso Scale Discovery (MSD). Results: Our findings show that genetic deletion of Il10 promotes enhanced neuroinflammation and tau phosphorylation. First, LPS-induced tau hyperphosphorylation was significantly increased in Il10−/− mice compared to controls. Second, LPS- treated Il10−/− mice showed signs of neurodegeneration. Third, LPS-treated Il10−/− mice showed robust IL-6 upregulation and direct treatment of primary neurons with IL-6 resulted in tau hyperphosphorylation on Ser396/Ser404 site. Conclusions: These data support that loss of IL-10 activates microglia, enhances IL-6, and leads to hyperphosphorylation of tau on AD-relevant epitopes in response to acute systemic inflammation.