University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Alma Burlingame, PhD

Alma Burlingame, PhD

Professor, Departments of Chemistry and Pharmaceutical Chemistry, UCSF

Cancer Center Program Memberships

Non-aligned

Research Summary

My group has long-standing, extensive expertise and experience in mass spectrometry, proteomics and systems biology, especially focused on sequencing, identification and study of unknown proteins, and the detection, assignment and site-specific dynamics of posttranslational modifications of proteins, particularly OGlcNAcylation, phosphorylation, acetylation, methylation and ubiquitinylation. Over many years we have collaborated with the neurobiological community extensively, including structural characterization of the GPI membrane anchor of the prion protein, structure of the lysyl oxidase co-factor, identification and PTM regulation of proteins in the retrograde signaling complexes in damaged axons, the O-GlcNAc/phosphorylation dynamics at the murine synapse, identification of new proteins involved in the Nodes of Ranvier, etc.

In addition to the work in proteomics and epigenetics above, we have focused significant effort on other studies concerning the architecture of protein complexes and machines for which angstrom resolution structural information has not yet been tractable. For example we have developed a new lysine-lysine cross-linking strategy based on chemical reductive amination that provides comprehensive sequence and cross-link site assignments using electron transfer dissociation (ETD). This information provides accurate distance constraints that complement cryoEM and computer modeling efforts. In parallel software algorithms and scoring strategies have been developed that greatly facilitates the assignment of cross-linked peptides in general. Very recently we have initiated a thrust into development and application of methodology to measure protein complexes directly in the gas phase using a newly acquired high mass Orbitrap Exactive instrument (m/z < 22,000). This effort will complement our long-standing work on chemical cross-linking of protein complexes and machines.

Finally, we have developed a general suite of programs and software tools required for processing large scale mass spectral data sets (HCD, ETD, etc) and stable isotopic labeling experiments (SILAC, iTRAQ, etc) called Protein Prospector.

Education

University of Rhode Island, Kingston, RI, B.S. 1959, Chemistry
MIT, Cambridge, MA, Ph.D., 1962, Chemistry, Physics


Professional Experience

  • 1963-68
    Asst. Professor of Chemistry, U. C. Berkeley, Dept. of Chemistry & Space Sciences Lab
  • 1968-72
    Assoc. Research Chemist, Space Sciences Lab., U.C. Berkeley
  • 1972-84
    Research Chemist, Space Sciences Lab., U.C. Berkeley
  • 1973-84
    Director, Biomedical Mass Spectrometry Resource, Space Sciences Lab., U. C. Berkeley
  • 1978-81
    Adjunct Professor of Chemistry & Pharmaceutical Chemistry, U. C. San Francisco
  • 1978-present
    Director, Biomedical Mass Spectrometry Resource, School of Pharmacy, U. C. San Francisco
  • 1980-present
    Member, The Liver Center, School of Medicine, U. C. San Francisco
  • 1981-present
    Professor of Chemistry & Pharmaceutical Chemistry, U. C. San Francisco
  • 1993-94
    Visiting Professor, Ludwig Institute for Cancer Research, London, UK
  • 1996-2003
    Professor of Biochemistry, University College, London
  • 2006-present
    Member, UCSF Helen Diller Family Comprehensive Cancer Center

Honors & Awards

  • 1970-72
    Guggenheim Fellow, Karolinska Institute, Stockholm
  • 1990-
    Elected Fellow, American Association for the Advancement of Science1999-2006
    Deputy Editor, Molecular and Cellular Proteomics
  • 2002-04
    Physiological Chemistry Study Section CSR, NIH
  • 2006-
    Co-editor, Molecular and Cellular Proteomics

Selected Publications

  1. Leon J, Moreno AJ, Garay BI, Chalkley RJ, Burlingame AL, Wang D, Dubal DB. Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and a-Synuclein Transgenic Mice. Cell Rep. 2017 Aug 08; 20(6):1360-1371.
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  2. Hasdemir B, Mahajan S, Oses-Prieto J, Chand S, Woolley M, Burlingame A, Grammatopoulos DK, Bhargava A. Actin cytoskeleton-dependent regulation of corticotropin-releasing factor receptor heteromers. Mol Biol Cell. 2017 Sep 01; 28(18):2386-2399.
    View on PubMed
  3. Larson AG, Elnatan D, Keenen MM, Trnka MJ, Johnston JB, Burlingame AL, Agard DA, Redding S, Narlikar GJ. Liquid droplet formation by HP1a suggests a role for phase separation in heterochromatin. Nature. 2017 Jul 13; 547(7662):236-240.
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  4. Zhou CY, Stoddard CI, Johnston JB, Trnka MJ, Echeverria I, Palovcak E, Sali A, Burlingame AL, Cheng Y, Narlikar GJ. Regulation of Rvb1/Rvb2 by a Domain within the INO80 Chromatin Remodeling Complex Implicates the Yeast Rvbs as Protein Assembly Chaperones. Cell Rep. 2017 Jun 06; 19(10):2033-2044.
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  5. Ni W, Xu SL, González-Grandío E, Chalkley RJ, Huhmer AFR, Burlingame AL, Wang ZY, Quail PH. PPKs mediate direct signal transfer from phytochrome photoreceptors to transcription factor PIF3. Nat Commun. 2017 May 11; 8:15236.
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  6. Xu SL, Chalkley RJ, Maynard JC, Wang W, Ni W, Jiang X, Shin K, Cheng L, Savage D, Hühmer AF, Burlingame AL, Wang ZY. Proteomic analysis reveals O-GlcNAc modification on proteins with key regulatory functions in Arabidopsis. Proc Natl Acad Sci U S A. 2017 Feb 21; 114(8):E1536-E1543.
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  7. Lechler MC, Crawford ED, Groh N, Widmaier K, Jung R, Kirstein J, Trinidad JC, Burlingame AL, David DC. Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging. Cell Rep. 2017 Jan 10; 18(2):454-467.
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  8. Yadav S, Oses-Prieto JA, Peters CJ, Zhou J, Pleasure SJ, Burlingame AL, Jan LY, Jan YN. TAOK2 Kinase Mediates PSD95 Stability and Dendritic Spine Maturation through Septin7 Phosphorylation. Neuron. 2017 Jan 18; 93(2):379-393.
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  9. Zhao Q, Ouyang X, Wan X, Gajiwala KS, Kath JC, Jones LH, Burlingame AL, Taunton J. Broad-Spectrum Kinase Profiling in Live Cells with Lysine-Targeted Sulfonyl Fluoride Probes. J Am Chem Soc. 2017 Jan 18; 139(2):680-685.
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  10. Urisman A, Levin RS, Gordan JD, Webber JT, Hernandez H, Ishihama Y, Shokat KM, Burlingame AL. An Optimized Chromatographic Strategy for Multiplexing In Parallel Reaction Monitoring Mass Spectrometry: Insights from Quantitation of Activated Kinases. Mol Cell Proteomics. 2017 Feb; 16(2):265-277.
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  11. Doll S, Urisman A, Oses-Prieto JA, Arnott D, Burlingame AL. Quantitative Proteomics Reveals Fundamental Regulatory Differences in Oncogenic HRAS and Isocitrate Dehydrogenase (IDH1) Driven Astrocytoma. Mol Cell Proteomics. 2017 Jan; 16(1):39-56.
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  12. Barrette AM, Roberts JK, Chapin C, Egan EA, Segal MR, Oses-Prieto JA, Chand S, Burlingame AL, Ballard PL. Antiinflammatory Effects of Budesonide in Human Fetal Lung. Am J Respir Cell Mol Biol. 2016 Nov; 55(5):623-632.
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  13. Bu SL, Liu C, Liu N, Zhao JL, Ai LF, Chi H, Li KL, Chien CW, Burlingame AL, Zhang SW, Wang ZY. Immuno-purification mass spectrometry identifies protein phosphatase 2A (PP2A) and BIN2/GSK3 as regulators of AKS transcription factors in Arabidopsis. Mol Plant. 2016 Oct 18.
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  14. Kim S, Maynard JC, Sasaki Y, Strickland A, Sherman DL, Brophy PJ, Burlingame AL, Milbrandt J. Schwann Cell O-GlcNAc Glycosylation Is Required for Myelin Maintenance and Axon Integrity. J Neurosci. 2016 Sep 14; 36(37):9633-46.
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  15. Maynard JC, Burlingame AL, Medzihradszky KF. Cysteine S-linked N-acetylglucosamine (S-GlcNAcylation), A New Post-translational Modification in Mammals. Mol Cell Proteomics. 2016 Nov; 15(11):3405-3411.
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  16. Li S, Yen L, Pastor WA, Johnston JB, Du J, Shew CJ, Liu W, Ho J, Stender B, Clark AT, Burlingame AL, Daxinger L, Patel DJ, Jacobsen SE. Mouse MORC3 is a GHKL ATPase that localizes to H3K4me3 marked chromatin. Proc Natl Acad Sci U S A. 2016 Aug 30; 113(35):E5108-16.
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  17. Levin RS, Hertz NT, Burlingame AL, Shokat KM, Mukherjee S. Innate immunity kinase TAK1 phosphorylates Rab1 on a hotspot for posttranslational modifications by host and pathogen. Proc Natl Acad Sci U S A. 2016 Aug 16; 113(33):E4776-83.
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  18. Perry RB, Rishal I, Doron-Mandel E, Kalinski AL, Medzihradszky KF, Terenzio M, Alber S, Koley S, Lin A, Rozenbaum M, Yudin D, Sahoo PK, Gomes C, Shinder V, Geraisy W, Huebner EA, Woolf CJ, Yaron A, Burlingame AL, Twiss JL, Fainzilber M. Nucleolin-Mediated RNA Localization Regulates Neuron Growth and Cycling Cell Size. Cell Rep. 2016 Aug 09; 16(6):1664-1676.
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  19. Lee S, Shang Y, Redmond SA, Urisman A, Tang AA, Li KH, Burlingame AL, Pak RA, Jovicic A, Gitler AD, Wang J, Gray NS, Seeley WW, Siddique T, Bigio EH, Lee VM, Trojanowski JQ, Chan JR, Huang EJ. Activation of HIPK2 Promotes ER Stress-Mediated Neurodegeneration in Amyotrophic Lateral Sclerosis. Neuron. 2016 Jul 06; 91(1):41-55.
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  20. Burlingame AL. On Strengthening the MCP Editorial Leadership. Mol Cell Proteomics. 2016 07; 15(7):2214-6.
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