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. Gleason CE, Oses-Prieto JA, Li KH, Saha B, Situ G, Burlingame AL, Pearce D. Phosphorylation at distinct subcellular locations underlies specificity in mTORC2 activation of SGK1 and Akt. J Cell Sci. 2019 Mar 05.
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  2. Tao W, Ma C, Bemben MA, Li KH, Burlingame AL, Zhang M, Nicoll RA. Mechanisms underlying the synaptic trafficking of the glutamate delta receptor GluD1. Mol Psychiatry. 2019 Mar 01.
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  3. Gierasch LM, Davidson NO, Rye KA, Burlingame AL. For the sake of science. J Biol Chem. 2019 Feb 22; 294(8):2976.
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  4. Gierasch LM, Davidson NO, Rye KA, Burlingame AL. For the sake of science. J Lipid Res. 2019 Feb 13.
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  5. Gierasch LM, Davidson NO, Rye KA, Burlingame AL. For the sake of science. Mol Cell Proteomics. 2019 Feb 13.
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  6. Liu B, Salgado OC, Singh S, Hippen KL, Maynard JC, Burlingame AL, Ball LE, Blazar BR, Farrar MA, Hogquist KA, Ruan HB. The lineage stability and suppressive program of regulatory T cells require protein O-GlcNAcylation. Nat Commun. 2019 01 21; 10(1):354.
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  7. Wong AW, Urisman A, Burlingame AL, Shokat KM. Chemically reprogramming the phospho-transfer reaction to crosslink protein kinases to their substrates. Protein Sci. 2019 Jan 13.
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  8. Longbotham JE, Chio CM, Dharmarajan V, Trnka MJ, Torres IO, Goswami D, Ruiz K, Burlingame AL, Griffin PR, Fujimori DG. Histone H3 binding to the PHD1 domain of histone demethylase KDM5A enables active site remodeling. Nat Commun. 2019 01 09; 10(1):94.
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  9. Han TW, Ye W, Bethel NP, Zubia M, Kim A, Li KH, Burlingame AL, Grabe M, Jan YN, Jan LY. Chemically induced vesiculation as a platform for studying TMEM16F activity. Proc Natl Acad Sci U S A. 2019 01 22; 116(4):1309-1318.
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  10. Butler VJ, Salazar DA, Soriano-Castell D, Alves-Ferreira M, Dennissen FJA, Vohra M, Oses-Prieto JA, Li KH, Wang AL, Jing B, Li B, Groisman A, Gutierrez E, Mooney S, Burlingame AL, Ashrafi K, Mandelkow EM, Encalada SE, Kao AW. Tau/MAPT disease-associated variant A152T alters tau function and toxicity via impaired retrograde axonal transport. Hum Mol Genet. 2018 Dec 26.
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  11. Nayak A, Kim DY, Trnka MJ, Kerr CH, Lidsky PV, Stanley DJ, Rivera BM, Li KH, Burlingame AL, Jan E, Frydman J, Gross JD, Andino R. A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute Activity and Stability. Cell Host Microbe. 2018 Oct 10; 24(4):542-557.e9.
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  12. Su Y, Liu Y, Behrens CR, Bidlingmaier S, Lee NK, Aggarwal R, Sherbenou DW, Burlingame AL, Hann BC, Simko JP, Premasekharan G, Paris PL, Shuman MA, Seo Y, Small EJ, Liu B. Targeting CD46 for both adenocarcinoma and neuroendocrine prostate cancer. JCI Insight. 2018 Sep 06; 3(17).
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  13. Sahoo PK, Lee SJ, Jaiswal PB, Alber S, Kar AN, Miller-Randolph S, Taylor EE, Smith T, Singh B, Ho TS, Urisman A, Chand S, Pena EA, Burlingame AL, Woolf CJ, Fainzilber M, English AW, Twiss JL. Axonal G3BP1 stress granule protein limits axonal mRNA translation and nerve regeneration. Nat Commun. 2018 08 22; 9(1):3358.
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  14. Lee SJ, Oses-Prieto JA, Kawaguchi R, Sahoo PK, Kar AN, Rozenbaum M, Oliver D, Chand S, Ji H, Shtutman M, Miller-Randolph S, Taylor RJ, Fainzilber M, Coppola G, Burlingame AL, Twiss JL. hnRNPs Interacting with mRNA Localization Motifs Define Axonal RNA Regulons. Mol Cell Proteomics. 2018 Nov; 17(11):2091-2106.
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  15. Sanlorenzo M, Vujic I, Esteve-Puig R, Lai K, Vujic M, Lin K, Posch C, Dimon M, Moy A, Zekhtser M, Johnston K, Gho D, Ho W, Gajjala A, Oses Prieto J, Burlingame A, Daud A, Rappersberger K, Ortiz-Urda S. The lincRNA MIRAT binds to IQGAP1 and modulates the MAPK pathway in NRAS mutant melanoma. Sci Rep. 2018 Jul 19; 8(1):10902.
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  16. Kim S, Maynard JC, Strickland A, Burlingame AL, Milbrandt J. Schwann cell O-GlcNAcylation promotes peripheral nerve remyelination via attenuation of the AP-1 transcription factor JUN. Proc Natl Acad Sci U S A. 2018 07 31; 115(31):8019-8024.
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  17. Burlingame A, Carr S, Gingras AC. Gaining an Easy Visual Grasp on MCP Content. Mol Cell Proteomics. 2018 Jul; 17(7):1259-1260.
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  18. Katsuno Y, Qin J, Oses-Prieto J, Wang H, Jackson-Weaver O, Zhang T, Lamouille S, Wu J, Burlingame A, Xu J, Derynck R. Arginine methylation of SMAD7 by PRMT1 in TGF-ß-induced epithelial-mesenchymal transition and epithelial stem-cell generation. J Biol Chem. 2018 Aug 24; 293(34):13059-13072.
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  19. Shurtleff MJ, Itzhak DN, Hussmann JA, Schirle Oakdale NT, Costa EA, Jonikas M, Weibezahn J, Popova KD, Jan CH, Sinitcyn P, Vembar SS, Hernandez H, Cox J, Burlingame AL, Brodsky JL, Frost A, Borner GH, Weissman JS. The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins. Elife. 2018 05 29; 7.
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  20. Laks DR, Oses-Prieto JA, Alvarado AG, Nakashima J, Chand S, Azzam DB, Gholkar AA, Sperry J, Ludwig K, Condro MC, Nazarian S, Cardenas A, Shih MYS, Damoiseaux R, France B, Orozco N, Visnyei K, Crisman TJ, Gao F, Torres JZ, Coppola G, Burlingame AL, Kornblum HI. A molecular cascade modulates MAP1B and confers resistance to mTOR inhibition in human glioblastoma. Neuro Oncol. 2018 05 18; 20(6):764-775.
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