Qitao Ran, Ph.D.

Reactive oxygen species (ROS) such as superoxide and hydrogen peroxide are generated during metabolism by mitochondria and by enzymes such as lipoxygenases and NADPH oxidases. Although ROS at low levels may be beneficial by acting as secondary signaling molecules to regulate cellular functions, excessive amounts of ROS induce oxidative damages to cause cell injury and cell death. Neurons’ ravenous demand of energy necessitates high metabolic rates which result in high ROS production. Neurons also have a high load of lipids enriched with polyunsaturated fatty acids that are particularly vulnerable to attack by ROS. Pathological conditions such as accumulation of miss-folded proteins and inflammation can further exacerbate ROS generation in neurons. Indeed, increased ROS are well-demonstrated in neurodegenerative diseases such as Alzheimer’s disease (AD) and Amyotrophic Lateral Sclerosis (ALS), and oxidative damage is believed to be a key pathogenic factor for both. Despite this, antioxidants have so far been disappointing in clinical trials for treatments of neurodegenerative diseases.  The main research interest of Ran lab is to illustrate the key events/pathways triggered by ROS that are ultimately responsible for injury and demise of neurons. The goal of our investigation is to identify targets that can be exploited for developing efficacious treatments/interventions. For example, we recently showed that glutathione peroxidase (Gpx4), a master regulator of ferroptosis, is essential for the survival of neurons underlying ALS and AD, suggesting that those neurons are vulnerable to ferroptosis. We are currently trying to determine whether ferroptosis is a key mode of neuron degeneration in ALS and AD and whether ferroptosis and other cell death mechanisms can serve as targets for therapeutic development. 

• Professional Background

  Education

  • 2000 - Postdoctoral Fellowship - Molecular Biology - Baylor College of Medicine
  • 1995 - PhD - Cell Biology - Peking Union Medical College
  • 1990 - BS - Biology - Beijing Normal University

  Appointments

  • 9/2013 - Associate Professor with tenure - University of Texas Health San Antonio, Cellular & Structural Biology
  • 5/2007 - Research Health Scientist - Audie Murphy VA Hospital, South Texas Veterans Health Care SystemSan Antonio

• Instruction & Training

  • 10/2016 - Present, Intro to Research, The University of Texas Health Science Center
  • 4/2016 - Present, Fundamentals of Neuroscience I, The University of Texas Health Science Center
  • 10/2013 - Present, Ph.D. Dissertations Directed, The University of Texas Health Science Center
  • 9/2011 - Present, Fundamentals of Biomedical Sciences, The University of Texas Health Science Center
  • 12/2009 - Present, Biology of Aging, The University of Texas Health Science Center
  • 10/2009 - Present, Membership on Supervising Committee, UTHSCSA
  • 9/2008 - Present, Pre-Doctoral Student Supervision, UTHSCSA
  • 11/2006 - Present, Post-Doctoral Student Supervision, CSB department, UTHSCSA

• Research & Grants

  Grants

  Title: Membrane lipid peroxidation in pathogenesis of Alzheimer’s disease.

  Project #: 1R01AG064078

  Funding Agency: NIA, NIH

  Period: 08/2019 - 03/2024

  Grant Description: Lipid peroxidation is elevated in Alzheimer’s disease (AD) brains. The goal of this study is to establish the importance of membrane lipid peroxidation in neurodegeneration of AD and provide proof-of-concept evidence for the efficacy of Glutathione peroxidase 4 (Gpx4), a glutathione peroxidase that can suppress lipid peroxidation by directly reducing phospholipid hydroperoxides in membranes, as a target of intervention to retard progression of AD

   

  Title: Gpx4 and ferroptosis inhibition in retarding ALS

  Project #: I01 BX003507

  Funding Agency: Department of Veterans Affair 

  Period: 04/2018 - 03/2022

  Role: Principal Investigator                                                                

  Grant Description: The goal of this award is to determine whether inhibition of ferroptosis by Gpx4 overexpression and supplementation of a small molecule inhibitor of ferroptosis can ameliorate paralysis and delay death of ALS mice.

   

• Publications

  Dar NJ, Na R, Ran Q. Functional Deficits of 5×FAD Neural Stem Cells Are Ameliorated by Glutathione Peroxidase 4. Cells. 2022 May 28;11(11). 

  Ahn B, Ranjit R, Kneis P, Xu H, Piekarz KM, Freeman WM, Kinter M, Richardson A, Ran Q, Brooks SV, Van Remmen H. Scavenging mitochondrial hydrogen peroxide by peroxiredoxin 3 overexpression attenuates contractile dysfunction and muscle atrophy in a murine model of accelerated sarcopenia. Aging Cell. 2022 Mar;21(3):e13569. 

  Loeser RF, Coryell PR, Armstrong AR, Collins JA, Gopalakrishnan P, McDermott KA, Ran Q, Carlson CS. Overexpression of Peroxiredoxin 3 in Cartilage Reduces the Severity of Age-Related Osteoarthritis But Not Surgically Induced Osteoarthritis in Mice. ACR Open Rheumatol. 2022 Feb 22. 

  Schwärzler J, Mayr L, Radlinger B, Grabherr F, Philipp M, Texler B, Grander C, Ritsch A, Hunjadi M, Enrich B, Salzmann K, Ran Q, Huber L, Tilg H, Kaser S, and Adolph T. Adipocyte GPX4 protects against inflammation, hepatic insulin resistance and metabolic dysregulation. Int J Obes. 2022 (Lond). Jan 14. 

  Evans RC, Chen L, Na R, Yoo K, Ran Q. The Gpx4NIKO mouse is a versatile model for testing interventions targeting ferroptotic cell death of spinal motor neurons. Neurotoxicity Research. Neurotox Res. 2022 Jan 19. 

  Chen L, Dar NJ, Na R, Danae McLane K, Yoo K, Han X, Ran Q. Enhanced defense against ferroptosis ameliorates cognitive impairment and reduces neurodegeneration in 5xFAD mice. Free Radic Biol Med. 2022. Jan 6;180:1-12. 

  Cheff DM, Muotri A, Stockwell BR, Schmidt EE, Ran Q, Kartha RV, Johnson SC, Mittal P, Arner ESJ, Wigby KM, Hall MD, Ramesh SK. Development of therapies for rare genetic disorders of GPX4: roadmap and opportunities. Orphanet J Rare Dis. 2021 Oct 23;16(1):446. 

  Chen L, Na R, Danae McLane K, Thompson CS, Gao J, Wang X, Ran Q. Overexpression of ferroptosis defense enzyme Gpx4 retards motor neuron disease of SOD1G93A mice. Sci Rep. 2021 Jun 18;11(1):12890. 

  Pharaoh G, Brown JL, Sataranatarajan K, Kneis P, Bian J, Ranjit R, Hadad N, Georgescu C, Rabinovitch P, Ran Q, Wren JD, Freeman W, Kinter M, Richardson A, Van Remmen H. Targeting cPLA2 derived lipid hydroperoxides as a potential intervention for sarcopenia. Sci Rep. 2020 Aug 18;10(1):13968. 

  Mayr L, Grabherr F, Schwärzler J, Reitmeier I, Sommer F, Gehmacher T, Niederreiter L, He GW, Ruder B, Kunz KTR, Tymoszuk P, Hilbe R, Haschka D, Feistritzer C, Gerner RR, Enrich B, Przysiecki N, Seifert M, Keller MA, Oberhuber G, Sprung S, Ran Q, Koch R, Effenberger M, Tancevski I, Zoller H, Moschen AR, Weiss G, Becker C, Rosenstiel P, Kaser A, Tilg H, Adolph TE. Dietary lipids fuel GPX4-restricted enteritis resembling Crohn's disease. Nat Commun. 2020 Apr 14;11(1):1775. 

  Kang R, Zeng L, Zhu S, Xie Y, Liu J, Wen Q, Cao L, Xie M, Ran Q, Kroemer G, Wang H, Billiar TR, Jiang J, Tang D. Lipid Peroxidation Drives Gasdermin D- Mediated Pyroptosis in Lethal Polymicrobial Sepsis. Cell Host Microbe 2018 Jun;24(1):97-108..

  Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, Fulda S, Gascón S, Hatzios SK, Kagan VE, Noel K, Jiang X, Linkermann A, Murphy ME, Overholtzer M, Oyagi A, Pagnussat GC, Park J, Ran Q, Rosenfeld CS, Salnikow K, Tang D, Torti FM, Torti SV, Toyokuni S, Woerpel KA, Zhang DD..Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell 2017 Oct;171(2):273-285.

  Hambright WS, Fonseca RS, Chen L, Na R, Ran Q. Ablation of ferroptosis regulator glutathione peroxidase 4 in forebrain neurons promotes cognitive impairment and neurodegeneration. Redox Biol. 2017 Aug;12:8-17.

  Chen L, Hambright WS, Na R, Ran Q. Ablation of the Ferroptosis Inhibitor Glutathione Peroxidase 4 in Neurons Results in Rapid Motor Neuron Degeneration and Paralysis. J Biol Chem. 2015 Nov;290(47):28097-280106.

  Chen L, Na R, Ran Q. Enhanced defense against mitochondrial hydrogen peroxide attenuates age-associated cognition decline. Neurobiol Aging. 2014 May;35(11):2552-2561.

  Yoo SE, Chen L, Na R, Liu Y, Rios C, Van Remmen H, Richardson A, Ran Q. Gpx4 ablation in adult mice results in a lethal phenotype accompanied by neuronal loss in brain. Free Radic Biol Med 2012 May;52(9):1820-1827.

  Chen L, Yoo SE, Na R, Liu Y, Ran Q. Cognitive impairment and increased Aß levels induced by paraquat exposure are attenuated by enhanced removal of mitochondrial H(2)O(2). Neurobiol Aging 2012 Feb;33(2):432-432.