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 focuses 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.


PDX models reflect the proteome landscape of pediatric acute lymphoblastic leukemia but divert in select pathways
Journal of Experimental and Clinical Cancer Research
Uzozie, A.C. and Ergin, E.K. and Rolf, N. and Tsui, J. and Lorentzian, A. and Weng, S.S.H. and Nierves, L. and Smith, T.G. and Lim, C.J. and Maxwell, C.A. and Reid, G.S.D. and Lange, P.F.
DOI: 10.1186/s13046-021-01835-8

Detectability of Biotin Tags by LC-MS/MS
Journal of Proteome Research
Nierves, L. and Lange, P.F.
DOI: 10.1021/acs.jproteome.0c01049

Multi-Omic Approach to Identify Phenotypic Modifiers Underlying Cerebral Demyelination in X-Linked Adrenoleukodystrophy.
Frontiers in cell and developmental biology
Richmond PA and van der Kloet F and Vaz FM and Lin D and Uzozie A and Graham E and Kobor M and Mostafavi S and Moerland PD and Lange PF and van Kampen AHC and Wasserman WW and van Karnebeek CDM
DOI: 10.3389/fcell.2020.00520
PubMed: 32671069

Fold-Change Compression: An Unexplored But Correctable Quantitative Bias Caused by Nonlinear Electrospray Ionization Responses in Untargeted Metabolomics.
Analytical chemistry
Yu H and Xing S and Nierves L and Lange PF and Huan T
DOI: 10.1021/acs.analchem.0c00246
PubMed: 32319750

Multi-omic approach to identify phenotypic modifiers underlying cerebral demyelination in X-linked adrenoleukodystrophy
Richmond PA and van der Kloet F and Vaz FM and Lin D and Uzozie A and Graham EJ and Kobor MS and Mostafavi S and Moerland PD and Lange PF and van Kampen AHC and Wasserman WW and van Karnebeek C
DOI: 10.1101/2020.03.19.20035063

Sensitive Determination of Proteolytic Proteoforms in Limited Microscale Proteome Samples.
Molecular & cellular proteomics : MCP
DOI: 10.1074/mcp.TIR119.001560
PubMed: 31471496

Origins and clinical relevance of proteoforms in pediatric malignancies
Expert Review of Proteomics
Amanda Lorentzian and Anuli Uzozie and Philipp F. Lange
DOI: 10.1080/14789450.2019.1575206

Tumor Variant Identification That Accounts for the Unique Molecular Landscape of Pediatric Malignancies
JNCI Cancer Spectrum
Amanda Lorentzian and Jaclyn A Biegel and D Gigi Ostrow and Nina Rolf and Chi-Chao Liu and S Rod Rassekh and Rebecca J Deyell and Timothy Triche and Kirk R Schultz and Jacob Rozmus and Gregor S D Reid and C James Lim and Philipp F Lange and Christopher A Maxwell
DOI: 10.1093/jncics/pky079

HMMR acts in the PLK1-dependent spindle positioning pathway and supports neural development
Marisa Connell and Helen Chen and Jihong Jiang and Chia-Wei Kuan and Abbas Fotovati and Tony LH Chu and Zhengcheng He and Tess C Lengyell and Huaibiao Li and Torsten Kroll and Amanda M Li and Daniel Goldowitz and Lucien Frappart and Aspasia Ploubidou and Millan S Patel and Linda M Pilarski and Elizabeth M Simpson and Philipp F Lange and Douglas W Allan and Christopher A Maxwell
DOI: 10.7554/elife.28672

HMMR acts in the PLK1-dependent spindle positioning pathway and supports neural development
Connell, M. and Chen, H. and Jiang, J. and Kuan, C.-W. and Fotovati, A. and Chu, T.L.H. and He, Z. and Lengyell, T.C. and Li, H. and Kroll, T. and Li, A.M. and Goldowitz, D. and Frappart, L. and Ploubidou, A. and Patel, M.S. and Pilarski, L.M. and Simpson, E.M. and Lange, P.F. and Allan, D.W. and Maxwell, C.A.
DOI: 10.7554/eLife.28672

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 Biology
DOI: 10.1016/j.matbio.2015.09.003

TAILS N-Terminomics and Proteomics Show Protein Degradation Dominates over Proteolytic Processing by Cathepsins in Pancreatic Tumors
Cell Reports
Prudova, A. and Gocheva, V. and auf dem Keller, U. and Eckhard, U. and Olson, O.C. and Akkari, L. and Butler, G.S. and Fortelny, N. and Lange, P.F. and Mark, J.C. and Joyce, J.A. and Overall, C.M.
DOI: 10.1016/j.celrep.2016.06.086

Active site specificity profiling datasets of matrix metalloproteinases (MMPs) 1, 2, 3, 7, 8, 9, 12, 13 and 14
Data in Brief
Eckhard, U. and Huesgen, P.F. and Schilling, O. and Bellac, C.L. and Butler, G.S. and Cox, J.H. and Dufour, A. and Goebeler, V. and Kappelhoff, R. and auf dem Keller, U. and Klein, T. and Lange, P.F. and Marino, G. and Morrison, C.J. and Prudova, A. and Rodriguez, D. and Starr, A.E. and Wang, Y. and Overall, C.M.
DOI: 10.1016/j.dib.2016.02.036

Proteome TopFIND 3.0 with TopFINDer and PathFINDer: database and analysis tools for the association of protein termini to pre- and post-translational events
Nucleic Acids Research
DOI: 10.1093/nar/gku1012

Active Site Specificity Profiling of the Matrix Metalloproteinase Family: Proteomic Identification of 4,300 Cleavage Sites by MMPs 1, 2, 3, 7, 8, 9, 12, 13, and 14.

LysargiNase mirrors trypsin for protein C-terminal and methylation-site identification
Nature Methods
Pitter F Huesgen and Philipp F Lange and Lindsay D Rogers and Nestor Solis and Ulrich Eckhard and Oded Kleifeld and Theodoros Goulas and F Xavier Gomis-Rüth and Christopher M Overall
DOI: 10.1038/nmeth.3177

Ensembles of protein termini and specific proteolytic signatures as candidate biomarkers of disease.
Huesgen PF and Lange PF and Overall CM
DOI: 10.1002/prca.201300104
PubMed: 24497460

Annotating N termini for the human proteome project: N termini and Na-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome
Journal of Proteome Research
Lange, P.F. and Huesgen, P.F. and Nguyen, K. and Overall, C.M.
DOI: 10.1021/pr401191w

Macrophage matrix metalloproteinase-12 dampens inflammation and neutrophil influx in arthritis
Cell Reports
Bellac, C.L. and Dufour, A. and Krisinger, M.J. and Loonchanta, A. and Starr, A.E. and auf dem Keller, U. and Lange, P.F. and Goebeler, V. and Kappelhoff, R. and Butler, G.S. and Burtnick, L.D. and Conway, E.M. and Roberts, C.R. and Overall, C.M.
DOI: 10.1016/j.celrep.2014.09.006

Network Analyses Reveal Pervasive Functional Regulation Between Proteases in the Human Protease Web
PLoS Biology
Fortelny, N. and Cox, J.H. and Kappelhoff, R. and Starr, A.E. and Lange, P.F. and Pavlidis, P. and Overall, C.M.
DOI: 10.1371/journal.pbio.1001869

LysargiNase and tryptic digest of MDA-MB 231 cell lysates

Characterization of LysargiNase for use in phosphoproteomics experiments, partII

Protein TAILS: when termini tell tales of proteolysis and function.
Lange PF and Overall CM
DOI: 10.1016/j.cbpa.2012.11.025
PubMed: 23298954

Proteomic Amino-Termini Profiling Reveals Targeting Information for Protein Import into Complex Plastids
Huesgen, P.F. and Alami, M. and Lange, P.F. and Foster, L.J. and Schr{\"o}der, W.P. and Overall, C.M. and Green, B.R.
DOI: 10.1371/journal.pone.0074483

TopFIND 2.0-linking protein termini with proteolytic processing and modifications altering protein function
Nucleic Acids Research
Lange, Philipp F. and Huesgen, Pitter F. and Overall, Christopher M.
DOI: 10.1093/nar/gkr1025

TopFIND, a knowledgebase linking protein termini with function
Nature Methods
Lange, Philipp F. and Overall, Christopher M.
DOI: 10.1038/nmeth.1669

Towards kit-like 18F-labeling of marimastat, a noncovalent inhibitor drug for in vivo PET imaging cancer associated matrix metalloproteases
Li, Y. and Ting, R. and Harwig, C.W. and Auf Dem Keller, U. and Bellac, C.L. and Lange, P.F. and Inkster, J.A.H. and Schaffer, P. and Adam, M.J. and Ruth, T.J. and Overall, C.M. and Perrin, D.M.
DOI: 10.1039/c1md00117e

Novel Matrix Metalloproteinase Inhibitor [(18)F]Marimastat-Aryltrifluoroborate as a Probe for In vivo Positron Emission Tomography Imaging in Cancer
Cancer Research
DOI: 10.1158/0008-5472.CAN-10-1584

ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function
GBM Annual Spring meeting Mosbach 2007
Jens C. Fuhrmann and Philipp F. Lange and Lena Wartosch and Thomas J. Jentsch
DOI: 10.1240/sav_gbm_2007_m_001701

ClC-7 requires Ostm1 as a beta-subunit to support bone resorption and lysosomal function
DOI: 10.1038/nature04535

Detectability of biotin tags by LC-MS/MS
Lorenz Nierves and Philipp F. Lange
DOI: 10.1101/2020.12.30.424786


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.


"Proteolytic protein termini as a new strategy for cancer cell-specific therapy," Innovation Grant, Canadian Cancer Society, 2016-2018

"Bioinformatics resources for genomewide assessment of protein function at the proteoform level," NSERC Discovery Grant, $28,000/ year, 2018-2023

Honours & Awards

Michael Smith Health Foundation Research Scholar Award (2016)

Canada Research Chair Tier 2 Award in Translational Proteomics of Childhood Malignancies (2015-2020)

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

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

Research Group Members

Georgina Barnabas
Enes Kemal Ergin, Graduate Student
Lina Jenane, Graduate Student
Amanda Lorentzian, Graduate student
Lorenz Nierves, Graduate Student
Ye Su, Graduate Student
Brenda Tse, Research Coordinator
Janice Tsui, Research Technician
Anuli Uzozie, Postdoctoral Fellow
Moones Yadegari, Masters Student