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. 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 J, Frost A, Borner GH, Weissman JS. The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins. Elife. 2018 May 29; 7.
    View on PubMed
  2. Rozenbaum M, Rajman M, Rishal I, Koppel I, Koley S, Medzihradszky KF, Oses-Prieto JA, Kawaguchi R, Amieux PS, Burlingame AL, Coppola G, Fainzilber M. Translatome Regulation in Neuronal Injury and Axon Regrowth. eNeuro. 2018 Mar-Apr; 5(2).
    View on PubMed
  3. Gamarra N, Johnson SL, Trnka MJ, Burlingame AL, Narlikar GJ. The nucleosomal acidic patch relieves auto-inhibition by the ISWI remodeler SNF2h. Elife. 2018 Apr 17; 7.
    View on PubMed
  4. Terenzio M, Koley S, Samra N, Rishal I, Zhao Q, Sahoo PK, Urisman A, Marvaldi L, Oses-Prieto JA, Forester C, Gomes C, Kalinski AL, Di Pizio A, Doron-Mandel E, Perry RB, Koppel I, Twiss JL, Burlingame AL, Fainzilber M. Locally translated mTOR controls axonal local translation in nerve injury. Science. 2018 03 23; 359(6382):1416-1421.
    View on PubMed
  5. Bulut-Karslioglu A, Macrae TA, Oses-Prieto JA, Covarrubias S, Percharde M, Ku G, Diaz A, McManus MT, Burlingame AL, Ramalho-Santos M. The Transcriptionally Permissive Chromatin State of Embryonic Stem Cells Is Acutely Tuned to Translational Output. Cell Stem Cell. 2018 Mar 01; 22(3):369-383.e8.
    View on PubMed
  6. MacRae AJ, Mayerle M, Hrabeta-Robinson E, Chalkley RJ, Guthrie C, Burlingame AL, Jurica M. Prp8 positioning of U5 snRNA is linked to 5' splice site recognition. RNA. 2018 Feb 27.
    View on PubMed
  7. Forester CM, Zhao Q, Phillips NJ, Urisman A, Chalkley RJ, Oses-Prieto JA, Zhang L, Ruggero D, Burlingame AL. Revealing nascent proteomics in signaling pathways and cell differentiation. Proc Natl Acad Sci U S A. 2018 Mar 06; 115(10):2353-2358.
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  8. 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. 2017 Nov 09.
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  9. Huang CY, Zhang C, Ho TS, Oses-Prieto J, Burlingame AL, Lalonde J, Noebels JL, Leterrier C, Rasband MN. aII Spectrin Forms a Periodic Cytoskeleton at the Axon Initial Segment and Is Required for Nervous System Function. J Neurosci. 2017 Nov 22; 37(47):11311-11322.
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  10. Lu F, Shao G, Wang Y, Guan S, Burlingame AL, Liu X, Liang X, Knox R, Ferriero DM, Jiang X. Hypoxia-ischemia modifies postsynaptic GluN2B-containing NMDA receptor complexes in the neonatal mouse brain. Exp Neurol. 2018 Jan; 299(Pt A):65-74.
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  11. 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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  12. 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.
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  13. 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 07 13; 547(7662):236-240.
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  14. 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 06 06; 19(10):2033-2044.
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  15. 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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  16. Shao G, Wang Y, Guan S, Burlingame AL, Lu F, Knox R, Ferriero DM, Jiang X. Proteomic Analysis of Mouse Cortex Postsynaptic Density following Neonatal Brain Hypoxia-Ischemia. Dev Neurosci. 2017; 39(1-4):66-81.
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  17. 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 02 21; 114(8):E1536-E1543.
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  18. 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 01 10; 18(2):454-467.
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  19. 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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  20. 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 01 18; 139(2):680-685.
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