• Lange, Philipp

    Titles

    Investigator, Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital
    Assistant Professor, Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of British Columbia
    Scientist, Michael Cuccione Childhood Cancer Research Program

    Degrees / Designations

    PhD

    Primary Area of Research
    Childhood Diseases
    Secondary Area(s) of Research
    Phone
    604-875-2000 ext. 6015
    Fax
    604-875-3120
    Lab Phone
    Mailing Address

    BC Children's Hospital Research Institute
    3082 - 950
    West 28th Avenue
    Vancouver, BC V5Z 4H4

    Research Areas
    • Childhood cancer
    • Cell signaling
    • Proteomics
    • Protein function
    • Post-translational protein modification
    • Targeted therapeutics
    Summary

    My research team strives to develop new diagnostic and therapeutic approaches to detect and treat children suffering from cancer earlier, better and with reduced impact on their life.

    The fundamental question is how cancer cells are different from healthy, normal cells? If we understand this we will be able to better detect and kill cancer while leaving the rest of the body untouched.

    Our research focusses on proteins, the structural and functional building blocks of a cell. To do this we combine genomics and proteomics, a technology that enables us to monitor all of the proteins in our body and detect how they are changed in childhood cancer. We then use computational approaches to further analyze and integrate our findings and to make them accessible to clinicians and fellow scientists around the world.

    Current Projects

    The overall objective of my team's research is to monitor and detect aberrant protein presence and function in cancer and exploit this difference to diagnose and treat cancer and improve the wellbeing of cancer survivors.

    We are particularly interested in how the post-translational modification of proteins affects cancer progression and secondary disease, which can hit childhood cancer survivors years after successful treatment. After translation proteins can be modified by, for example, proteolytic processing or phosphorylation. This creates a repertoire of "proteoforms", which are all the variant and modified protein products of a single gene. They often differ in their localization, function and interaction with other proteins.

    Our research program follows four main axes that inform each other:
    I: We use proteo-genomics to study differences in tissue specimen from children suffering from select cancers and healthy individuals, and translate these findings into a new diagnostic and treatment approach.
    II: We integrate cell biology, biochemistry, genomics, proteomics and bioinformatics to study the role of post-translational modification in the regulation of select cell signaling networks. By investigating patient-derived cells and mouse models we strive to identify new ways of altering these signaling networks to improve drug efficacy and reduce side effects.
    III: Computational biology plays an integral role in our research. Our main focus is the development of algorithms for multi-scale data integraction, protein function analysis, pattern recognition and de-convolution of network effects in complex systems. Building on these we develop new biological knowledgebases and applications to improve the functional analysis of genomics and proteomics data and to guide personalized treatment decisions. 
    IV: We continuously strive to improve existing- and develop new technologies for the mass spectrometric analysis of complex biological specimen enabling a more comprehensive, specific and sensitive investigation of smaller biopsies.

    My research team is embedded in the Michael Cuccione Childhood Cancer Research Program and affiliated with the BC Cancer Research Centre and BC Children’s Hospital. This creates a stimulating environment in which we work closely with world-class experts in clinical oncology, cancer biology, genomics and computer sciences.

    Selected Publications

    For the latest publications, please visit Dr. Lange’s ORCID profile.

    Fotelny N, Yang S., Pavlidis P, Lange PF#, Overall CM# (2015) TopFIND 3.0 – a platform for functional data analysis of shotgun and termini oriented proteomics data Nucleic Acids Research 43(D1): D290-D297 (# joint corresponding author)

    Huesgen PF, Lange PF, Rogers LD, Solis N, Eckhard U, Kleifeld O, Goulas T, Gomis-Rüth FX, Overall CM (2015) LysargiNase mirrors trypsin for identification of protein C-termini and methylation sites. Nature Methods 12(1): 55-58.

    Lange PF*, Huesgen PF*, Nguyen K, Overall CM (2014) Annotating N termini for the Human Proteome Project: N termini differentiate stable processed protein species from degradation remnants in the human erythrocyte proteome. Journal of Proteome Research 13 (4), 2028-2044 (* joint first authors)

    Huesgen PF, Lange PF, Overall CM (2014) Ensembles of protein termini are sensitive and specific proteolytic signature biomarkers of disease, Proteomics – Clinical Applications 8 (5-6), 338-350 (* joint first authors)

    Lange PF, Overall CM (2013) Protein TAILS: When termini tell tales of proteolysis and function. Current Opinion in Chemical Biology 17(1):73-82.

    Lange PF, Huesgen PF, Overall CM# (2012) TopFIND 2.0—linking protein termini with proteolytic processing and modifications altering protein function. Nucleic Acids Research. 40(D1): D351-D361 (# joint corresponding authors).

    Lange PF, Overall CM (2011) TopFIND, a knowledgebase linking protein termini with function. Nature Methods 8(9): 703–704.

    auf dem Keller U*, Bellac CL*, Li Y, Lou Y, Lange PF, Ting R, Harwig C, Kappelhoff R, Dedhar S, Adam MJ, Ruth TJ, Bénard F, Perrin DM, Overall CM (2010) Novel matrix metalloproteinase inhibitor [18F]marimastat-aryltrifluoroborate as a probe for in vivo positron emission tomography imaging in cancer. Cancer Research 1;70(19):7562-9 (*joint first authors)

    Lange PF, Wartosch L, Jentsch TJ, Fuhrmann JC (2006) ClC–7 requires Ostm1 as a ß–subunit to support bone resorption and lysosomal function. Nature 440: 220–223.

    Eckhard U, Huesgen PF, Schilling O, Bellac CL, Butler GS, Cox JH, Dufour A, Goebeler V, Kappelhoff R, Keller UA, Klein T, Lange PF, Marino G, Morrison CJ, Prudova A, Rodriguez D, Starr AE, Wang Y, Overall CM. Active site specificity profiling of the matrix metalloproteinase family: Proteomic identification of 4300 cleavage sites by nine MMPs explored with structural and synthetic peptide cleavage analyses. Matrix Biol. 2016 Jan. PMID: 26407638. Impact Factor: 4.47

    Grants
    Honours & Awards

    Nomination for the Canada Research Chair Tier II in 'Translational and Applied Genomics of Pediatric Malignancy'

    Joint Michael Smith Foundation for Health Research & Breast Cancer Society of Canada Research Award (2011-2012)

    Feodor Lynen Research Fellowship for Postdoctoral Research (Alexander von Humboldt Foundation) (2009-2011)

    Research Group Members
    • Enes Kemal Ergin – Graduate Student
    • Erin Kim – Student
    • Amanda Lorentzian – Graduate Student
    • Lorenz Nierves – Graduate Student
    • Theodore Smith – Graduate Student
    • Anuli Uzozie – Postdoctoral Fellow
    • Samuel Weng – Graduate Student