Ansgar B Siemer, PhD

Title(s)Associate Professor of Physiology and Neuroscience
SchoolKeck School of Medicine of Usc
AddressZNI 113, 1501 San Pablo Street
Health Sciences Campus
Los Angeles CA 90033
Phone+1 323 442 2720
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    Other Positions
    Title(s)Co-Director, Ph.D. Program in Medical Biophysics


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    The aim of my laboratory is to create a better understanding of the pathological and functional aspects of protein disorder and aggregation. In particular, we are interested in the differences between functional and pathological amyloid fibrils and the importance of intrinsically disordered protein domains (i.e. domains that lack stable tertiary or secondary structure) for the formation of amyloid.

    Amyloid formation is important for many neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's disease. The aggregation of monomeric proteins into a variety of oligomeric and fibrillar (amyloid) states can lead to cell death and, therefore, disease. However, amyloid fibrils can also have non-pathological, positive functions such as cell signaling or scaffolding functions. One of the most important goals of the lab is to understand what distinguishes functional and pathological amyloid fibrils. Understanding the difference between these types of amyloid could lead to the development of new therapeutics and will deepen our understanding of the role of amyloid in biology.

    A second area of research in my laboratory is protein disorder as prerequisite for amyloid formation. Intrinsic disorder or partial unfolding is necessary for a protein to aggregate from its soluble state into an amyloid fibril. Furthermore, many proteins can be forced to fold into an amyloid by partial denaturation in vitro. The structural aspects of the unfolded state is, therefore, important for the understanding of amyloid formation and may lead to new strategies to prevent the formation of amyloid in neurodegenerative diseases. However, partially unfolded, intrinsically disordered proteins also carry important functional aspects, especially in eukaryotic organisms, where up to 40% of all proteins contain disordered regions. Our second goal is to understand how aggregation is prevented in most disordered proteins and why it occurs in some disease-related cases.

    To address these questions, my lab will use primarily solid-state nuclear magnetic resonance (NMR) in conjunction with other biochemical methods. Solid-state NMR is an emerging technique that enables us to investigate protein structures that are otherwise inaccessible to atomic-resolution structural methods such as X-ray crystallography and liquid-state NMR, thereby permitting us to investigate systems such as protein fibrils with atomic resolution.

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    Collapse Research Activities and Funding
    Molecular Mechanism of Huntingtin Misfolding and its Inhibition by Designed and Cellular Proteins
    NIH R01NS120704Sep 17, 2021 - Aug 31, 2026
    Role: Co-Principal Investigator
    Structural characterization of A-beta strain variation in AD mouse models
    NIH R01AG061865Sep 30, 2018 - May 31, 2023
    Role: Principal Investigator
    Orb2 a functional amyloid in long-term memory: Its structure and how it forms
    NIH R01GM110521Sep 1, 2015 - May 31, 2021
    Role: Principal Investigator

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    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help. to make corrections and additions.
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    Altmetrics Details PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Calmodulin binds the N-terminus of the functional amyloid Orb2A inhibiting fibril formation. PLoS One. 2022; 17(1):e0259872. Soria MA, Cervantes SA, Siemer AB. PMID: 35025866; PMCID: PMC8758002.
      View in: PubMed   Mentions:    Fields:    Translation:AnimalsCells
    2. Huntingtin fibrils with different toxicity, structure, and seeding potential can be interconverted. Nat Commun. 2021 07 13; 12(1):4272. Mario Isas J, Pandey NK, Xu H, Teranishi K, Okada AK, Fultz EK, Rawat A, Applebaum A, Meier F, Chen J, Langen R, Siemer AB. PMID: 34257293; PMCID: PMC8277859.
      View in: PubMed   Mentions: 3     Fields:    Translation:Humans
    3. Droplet and fibril formation of the functional amyloid Orb2. J Biol Chem. 2021 07; 297(1):100804. Ashami K, Falk AS, Hurd C, Garg S, Cervantes SA, Rawat A, Siemer AB. PMID: 34044018; PMCID: PMC8294575.
      View in: PubMed   Mentions: 2     Fields:    Translation:AnimalsCells
    4. Structural Model of the Proline-Rich Domain of Huntingtin Exon-1 Fibrils. Biophys J. 2020 11 17; 119(10):2019-2028. Falk AS, Bravo-Arredondo JM, Varkey J, Pacheco S, Langen R, Siemer AB. PMID: 33096080; PMCID: PMC7732765.
      View in: PubMed   Mentions: 4     Fields:    Translation:Humans
    5. Advances in studying protein disorder with solid-state NMR. Solid State Nucl Magn Reson. 2020 04; 106:101643. Siemer AB. PMID: 31972419; PMCID: PMC7202078.
      View in: PubMed   Mentions: 4     Fields:    Translation:HumansAnimalsCells
    6. Dynamics of the Proline-Rich C-Terminus of Huntingtin Exon-1 Fibrils. J Phys Chem B. 2018 10 18; 122(41):9507-9515. Caulkins BG, Cervantes SA, Isas JM, Siemer AB. PMID: 30252478; PMCID: PMC6200332.
      View in: PubMed   Mentions: 8     Fields:    Translation:Cells
    7. The Structure of the Necrosome RIPK1-RIPK3 Core, a Human Hetero-Amyloid Signaling Complex. Cell. 2018 05 17; 173(5):1244-1253.e10. Mompeán M, Li W, Li J, Laage S, Siemer AB, Bozkurt G, Wu H, McDermott AE. PMID: 29681455; PMCID: PMC6002806.
      View in: PubMed   Mentions: 81     Fields:    Translation:HumansCells
    8. Metal Binding Properties of the N-Terminus of the Functional Amyloid Orb2. Biomolecules. 2017 08 01; 7(3). Bajakian TH, Cervantes SA, Soria MA, Beaugrand M, Kim JY, Service RJ, Siemer AB. PMID: 28763009; PMCID: PMC5618238.
      View in: PubMed   Mentions: 1     Fields:    Translation:AnimalsCells
    9. The Functional Amyloid Orb2A Binds to Lipid Membranes. Biophys J. 2017 Jul 11; 113(1):37-47. Soria MA, Cervantes SA, Bajakian TH, Siemer AB. PMID: 28700922; PMCID: PMC5510761.
      View in: PubMed   Mentions: 8     Fields:    Translation:AnimalsCells
    10. Formation and Structure of Wild Type Huntingtin Exon-1 Fibrils. Biochemistry. 2017 07 18; 56(28):3579-3586. Isas JM, Langen A, Isas MC, Pandey NK, Siemer AB. PMID: 28621522; PMCID: PMC5575822.
      View in: PubMed   Mentions: 15     Fields:    Translation:Humans
    11. Identification and Structural Characterization of the N-terminal Amyloid Core of Orb2 isoform A. Sci Rep. 2016 12 06; 6:38265. Cervantes SA, Bajakian TH, Soria MA, Falk AS, Service RJ, Langen R, Siemer AB. PMID: 27922050; PMCID: PMC5138630.
      View in: PubMed   Mentions: 18     Fields:    Translation:Cells
    12. Dynamic domains of amyloid fibrils can be site-specifically assigned with proton detected 3D NMR spectroscopy. J Biomol NMR. 2016 11; 66(3):159-162. Falk AS, Siemer AB. PMID: 27766502; PMCID: PMC5116245.
      View in: PubMed   Mentions: 5     Fields:    Translation:Cells
    13. Solid-State Nuclear Magnetic Resonance on the Static and Dynamic Domains of Huntingtin Exon-1 Fibrils. Biochemistry. 2015 Jun 30; 54(25):3942-9. Isas JM, Langen R, Siemer AB. PMID: 26020223; PMCID: PMC4770890.
      View in: PubMed   Mentions: 29     Fields:    Translation:HumansCells
    14. Characterization of prion-like conformational changes of the neuronal isoform of Aplysia CPEB. Nat Struct Mol Biol. 2013 Apr; 20(4):495-501. Raveendra BL, Siemer AB, Puthanveettil SV, Hendrickson WA, Kandel ER, McDermott AE. PMID: 23435382; PMCID: PMC5518672.
      View in: PubMed   Mentions: 37     Fields:    Translation:AnimalsCells
    15. Protein linewidth and solvent dynamics in frozen solution NMR. PLoS One. 2012; 7(10):e47242. Siemer AB, Huang KY, McDermott AE. PMID: 23077575; PMCID: PMC3471952.
      View in: PubMed   Mentions: 23     Fields:    Translation:Cells
    16. The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell. 2012 Jul 20; 150(2):339-50. Li J, McQuade T, Siemer AB, Napetschnig J, Moriwaki K, Hsiao YS, Damko E, Moquin D, Walz T, McDermott A, Chan FK, Wu H. PMID: 22817896; PMCID: PMC3664196.
      View in: PubMed   Mentions: 480     Fields:    Translation:HumansCells
    17. Homonuclear mixing sequences for perdeuterated proteins. J Magn Reson. 2011 Jan; 208(1):122-7. Huang KY, Siemer AB, McDermott AE. PMID: 21094063; PMCID: PMC3021637.
      View in: PubMed   Mentions: 12     Fields:    Translation:Cells
    18. Protein-ice interaction of an antifreeze protein observed with solid-state NMR. Proc Natl Acad Sci U S A. 2010 Oct 12; 107(41):17580-5. Siemer AB, Huang KY, McDermott AE. PMID: 20884853; PMCID: PMC2955146.
      View in: PubMed   Mentions: 17     Fields:    
    19. Solid-state NMR on a type III antifreeze protein in the presence of ice. J Am Chem Soc. 2008 Dec 24; 130(51):17394-9. Siemer AB, McDermott AE. PMID: 19053456.
      View in: PubMed   Mentions: 10     Fields:    Translation:AnimalsCells
    20. Amyloid fibrils of the HET-s(218-289) prion form a beta solenoid with a triangular hydrophobic core. Science. 2008 Mar 14; 319(5869):1523-6. Wasmer C, Lange A, Van Melckebeke H, Siemer AB, Riek R, Meier BH. PMID: 18339938.
      View in: PubMed   Mentions: 398     Fields:    Translation:AnimalsCells
    21. Improved resolution in (13)C solid-state spectra through spin-state-selection. J Magn Reson. 2007 Feb; 184(2):322-9. Verel R, Manolikas T, Siemer AB, Meier BH. PMID: 17088090.
      View in: PubMed   Mentions: 2     Fields:    
    22. Observation of highly flexible residues in amyloid fibrils of the HET-s prion. J Am Chem Soc. 2006 Oct 11; 128(40):13224-8. Siemer AB, Arnold AA, Ritter C, Westfeld T, Ernst M, Riek R, Meier BH. PMID: 17017802.
      View in: PubMed   Mentions: 47     Fields:    Translation:Cells
    23. 13C, 15N resonance assignment of parts of the HET-s prion protein in its amyloid form. J Biomol NMR. 2006 Feb; 34(2):75-87. Siemer AB, Ritter C, Steinmetz MO, Ernst M, Riek R, Meier BH. PMID: 16518695.
      View in: PubMed   Mentions: 41     Fields:    
    24. Correlation of structural elements and infectivity of the HET-s prion. Nature. 2005 Jun 09; 435(7043):844-8. Ritter C, Maddelein ML, Siemer AB, Lührs T, Ernst M, Meier BH, Saupe SJ, Riek R. PMID: 15944710; PMCID: PMC1567094.
      View in: PubMed   Mentions: 160     Fields:    Translation:AnimalsCells
    25. High-resolution solid-state NMR spectroscopy of the prion protein HET-s in its amyloid conformation. Angew Chem Int Ed Engl. 2005 Apr 15; 44(16):2441-4. Siemer AB, Ritter C, Ernst M, Riek R, Meier BH. PMID: 15770629.
      View in: PubMed   Mentions: 40     Fields:    Translation:Cells
    26. Conserved asparagine residue 54 of alpha-sarcin plays a role in protein stability and enzyme activity. Biol Chem. 2004 Dec; 385(12):1165-70. Siemer A, Masip M, Carreras N, García-Ortega L, Oñaderra M, Bruix M, Del Pozo AM, Gavilanes JG. PMID: 15653429.
      View in: PubMed   Mentions: 1     Fields:    Translation:Cells
    27. Fluoroalcohol-induced structural changes of proteins: some aspects of cosolvent-protein interactions. Eur Biophys J. 2001 Aug; 30(4):273-83. Gast K, Siemer A, Zirwer D, Damaschun G. PMID: 11548130.
      View in: PubMed   Mentions: 15     Fields:    Translation:AnimalsCells
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