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. Cuesta A, Wan X, Burlingame AL, Taunton J. Ligand Conformational Bias Drives Enantioselective Modification of a Surface-Exposed Lysine on Hsp90. J Am Chem Soc. 2020 Feb 03.
    View on PubMed
  2. Hamdan H, Lim BC, Torii T, Joshi A, Konning M, Smith C, Palmer DJ, Ng P, Leterrier C, Oses-Prieto JA, Burlingame AL, Rasband MN. Mapping axon initial segment structure and function by multiplexed proximity biotinylation. Nat Commun. 2020 Jan 03; 11(1):100.
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  3. Torii T, Ogawa Y, Liu CH, Ho TS, Hamdan H, Wang CC, Oses-Prieto JA, Burlingame AL, Rasband MN. NuMA1 promotes axon initial segment assembly through inhibition of endocytosis. J Cell Biol. 2019 Nov 14.
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  4. Loonat AA, Martin ED, Sarafraz-Shekary N, Tilgner K, Hertz NT, Levin R, Shokat KM, Burlingame AL, Arabacilar P, Uddin S, Thomas M, Marber MS, Clark JE. p38? MAPK contributes to left ventricular remodeling after pathologic stress and disinhibits calpain through phosphorylation of calpastatin. FASEB J. 2019 Dec; 33(12):13131-13144.
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  5. Sanulli S, Trnka MJ, Dharmarajan V, Tibble RW, Pascal BD, Burlingame AL, Griffin PR, Gross JD, Narlikar GJ. HP1 reshapes nucleosome core to promote phase separation of heterochromatin. Nature. 2019 11; 575(7782):390-394.
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  6. Meneses-Romero E, Hernández-Orihuela L, Pando-Robles V, López TD, Oses-Prieto JA, Burlingame AL, Batista CVF. Quantitative proteomic analysis reveals high interference on protein expression of H9c2 cells activated with glucose and cardiotonic steroids. J Proteomics. 2020 Jan 16; 211:103536.
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  7. Fu MM, McAlear TS, Nguyen H, Oses-Prieto JA, Valenzuela A, Shi RD, Perrino JJ, Huang TT, Burlingame AL, Bechstedt S, Barres BA. The Golgi Outpost Protein TPPP Nucleates Microtubules and Is Critical for Myelination. Cell. 2019 Sep 19; 179(1):132-146.e14.
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  8. Kim H, Yen L, Wongpalee SP, Kirshner JA, Mehta N, Xue Y, Johnston JB, Burlingame AL, Kim JK, Loparo JJ, Jacobsen SE. The Gene-Silencing Protein MORC-1 Topologically Entraps DNA and Forms Multimeric Assemblies to Cause DNA Compaction. Mol Cell. 2019 Aug 22; 75(4):700-710.e6.
    View on PubMed
  9. MacRae AJ, Coltri P, Hrabeta-Robinson E, Chalkley RJ, Burlingame AL, Jurica MS. A two-step probing method to compare lysine accessibility across macromolecular complex conformations. RNA Biol. 2019 10; 16(10):1346-1354.
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  10. Zhao JL, Zhang LQ, Liu N, Xu SL, Yue ZL, Zhang LL, Deng ZP, Burlingame AL, Sun DY, Wang ZY, Sun Y, Zhang SW. Mutual Regulation of Receptor-Like Kinase SIT1 and B'?-PP2A Shapes the Early Response of Rice to Salt Stress. Plant Cell. 2019 Sep; 31(9):2131-2151.
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  11. 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. 2019 05 01; 28(9):1498-1514.
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  12. Hernández-Ortega S, Sánchez-Botet A, Quandt E, Masip N, Gasa L, Verde G, Jiménez J, Levin RS, Rutaganira FU, Burlingame AL, Wolfgeher D, Ribeiro MPC, Kron SJ, Shokat KM, Clotet J. Phosphoregulation of the oncogenic protein regulator of cytokinesis 1 (PRC1) by the atypical CDK16/CCNY complex. Exp Mol Med. 2019 Apr 16; 51(4):44.
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  13. Gleason CE, Oses-Prieto JA, Li KH, Saha B, Situ G, Burlingame AL, Pearce D. Phosphorylation at distinct subcellular locations underlies specificity in mTORC2-mediated activation of SGK1 and Akt. J Cell Sci. 2019 Apr 09; 132(7).
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  14. 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 Oct; 24(10):1451-1460.
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  15. Gierasch LM, Davidson NO, Rye KA, Burlingame AL. For the Sake of Science. Mol Cell Proteomics. 2019 03; 18(3):406-407.
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  16. Gierasch LM, Davidson NO, Rye KA, Burlingame AL. For the sake of science. J Biol Chem. 2019 02 22; 294(8):2976.
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  17. Gierasch LM, Davidson NO, Rye KA, Burlingame AL. For the sake of science. J Lipid Res. 2019 Apr; 60(4):719-720.
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  18. Wong AW, Urisman A, Burlingame AL, Shokat KM. Chemically reprogramming the phospho-transfer reaction to crosslink protein kinases to their substrates. Protein Sci. 2019 03; 28(3):654-662.
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  19. 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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  20. 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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