• PhD equivalent, Universitat Witten / Herdecke, Germany. 2003
• MD, University of Muenster Medical School, Germany. 2001

Recent publications

Selected Publications

The research of my laboratory focuses on the molecular characterization of lymphoid cancers and biomarker discovery in a variety of Hodgkin and Non-Hodgkin Lymphoma subtypes. Our translational lymphoma research group uses a variety of state-of-the-art genome-wide discovery tools including array-based and digital gene expression profiling, single-nucleotide polymorphisms analysis and massively parallel sequencing techniques. A main research goal of the lab is to identify and functionally study underlying genetic mechanisms of immune privilege in lymphoid cancers. In previous work using next-generation sequencing, we identified several driver mutations and gene fusions, in particular, that have been shown to arise from specific chromosomal rearrangements in Hodgkin lymphoma and primary mediastinal large B cell lymphoma. Most of the identified genes (CIITA, CD274, PDCD1LG2) feature prominently in immune cell function impacting non-neoplastic cells in the tumor microenvironment. The discovery of these changes across a wide spectrum of lymphomas will likely reinforce the paradigm that immune privilege is a critical component of cancer phenotypes.

Another focus of the laboratory is on the specific composition of the tumor microenvironment in Hodgkin lymphoma. Using gene expression profiling and immunohistochemistry we have identified that the number of tumor-associated macrophages in lymph node biopsies is linked to unfavorable treatment outcome. However, many questions remain regarding the molecular mechanisms underlying the interaction of the malignant cells with infiltrating macrophages and immune cells in the microenvironment in general. Recently, CSF1R has been identified as a key molecule expressed on Hodgkin Reed Sternberg (HRS) cells and tumor-associated macrophages in Hodgkin lymphoma. We now seek to better describe the phenotype of tumour-associated macrophages found in lymphoma biopsies to shed more light on this tumor-microenvironment interaction and to test in-vitro if this cross-talk can be targeted by small molecule inhibitors.

Lymphoma relapse and progression is still one of the major clinical challenges in clinical care and our knowledge about the underlying biology of relapse is still rudimentary. Our preliminary data indicate that certain gene findings have developed during treatment and might be characteristic of this relapse biology. Therefore, we specifically focus on ongoing translational studies on lymphoma relapse biopsies using highly-annotated clinical data sets. By collaboration with our clinical colleagues, we are working on solutions how to develop better outcome predictors and predictive biomarkers that inform on individualized treatment options. These studies encompass biomarker evaluation in Hodgkin lymphoma, follicular lymphoma, large B cell lymphomas, and mantle cell lymphoma.

Collaborations
As a translational research laboratory, we pursue the goal of translating our research findings into better treatments for our patients. The Centre for Lymphoid Cancer (CLC) provides an excellent infrastructure to answer clinically relevant questions in collaboration with clinical oncologists (Joseph Connors, Laurie Sehn, Kerry Savage), hemato-pathologists (Randy Gascoyne), genome researchers (Marco Marra) and computational biologists (Sohrab Shah). The Centre for Translational and Applied Genomics (CTAG) and the Genome Sciences Centre (GSC) is providing cutting technology to facilitate translational research from bench to bedside. Multiple collaborations with researchers inside and outside the Cancer Agency complement the research focus areas to provide additional expertise in epigenomics (Martin Hirst) in vivo modeling (Steidl lab, Einstein College, NY), endogenous retroviruses and epigenetics (Mager lab, Terry-Fox Laboratory, BCCA), immune pathology (Anke van den Berg, Arjan Diepstra, University of Groningen, NL), and childhood lymphomas (Horton lab, Baylor College, Houston, TX).

Clinical Service

• Job opportunities

Projects:
Allen Distinguished Investigators (ADI Program)
Dr. Steidl was recognized as a pioneer scientist and received a prestigious award, the Allen Distinguished Investigators Award, from the Paul Allen Frontiers Group, a non-for-profit organization based in the United States, which invests in emerging frontiers in science. A total of $1.5 Million-USD was awarded to Dr. Steidl and his research team at BC Cancer to support a study of the dynamic, complex networks of normal and cancer cells constituting the tumor microenvironment using novel, multidimensional approaches. This project is in collaboration with a Cancer Imaging scientist, Dr. Akil Merchant at Cedars Sinai Medical Center and aims to comprehensively characterize the microenvironment composition and spatial architecture of cHL in correlation with somatic gene alterations in the malignant Hodgkin Reed Sternberg (HRS) cells to potentiate therapeutic advancements. Integration of the cutting edge technologies in single cell genomics and cancer imaging allows for simultaneous measurements of over 40 markers in primary patient samples at single cell resolution and unveils the complex spatial architecture and cellular crosstalk of this disease. This is the first-of-its-kind collaboration of bringing together two world-leading programs, which are focused on tumor microenvironment and cHL pathogenesis. The knowledge gained from this research will lead to development of novel biomarkers and immunotherapies targeting the tumor-host interactions, which will ultimately improve patient outcomes.

Lymphoma/Leukemia Molecular Profiling Project (LLMPP Program)
Diffuse large B cell lymphoma (DLBCL) is an aggressive form of B-cell non Hodgkin lymphoma (NHL) and the most common type of NHL. With its heterogeneous nature in clinical behavior, morphology and immunophenotype, reliable biomarkers are needed to accurately categorize the tumor subtypes. Recent advancement in gene expression profiling has defined clinically important predictive biomarkers based on “cell-of-origin” (COO), which categorizes DLBCL into 2 specific subtypes with distinct mutational patterns and clinical outcome. MYC and BCL2 translocations are other genomic characteristics which are used as an additional prognostic tool to further characterize the COO subtypes to determine prognosis for DLBCL patients. Recently, the team led by Dr. Scott has revealed the location of MYC rearrangement at base pair resolution by performing targeted sequencing of MYC, BCL2, BCL6 and IG loci. The team discovered a novel recurrent MYC partner, RFTN1, and identified clinically relevant architecture of MYC rearrangement in DLBCL (Chong et al., Blood Advances, 2018). To further dissect the subtypes of DLBCL, RNA sequencing, targeted sequencing and whole-exome sequencing data from 157 de novo GCB-DLBCLs were analyzed, and a new clinically relevant assay was developed based on 104-gene double-hit signatures (DHITsig). Our data showed that DHITsig positive patients have inferior outcomes compared to DHITsig negative patients. The new assay, DLBCL90, identifies a clinically and biologically distinct group within GCB-DLBCL characterized by a gene expression signature of high-grade B-cell lymphoma with double/triple hit (HGBL-DH/TH-BCL2) and helps guide clinical management of this aggressive disease (Ennishi et al., J. Clin. Oncol, 2018). The aim of this program is to improve patient outcomes by comprehensively characterizing the aggressive B-cell lymphoma subtypes and developing clinically relevant assays.

Overcoming Treatment Failure in Lymphoid Cancer (TFRI-funded Program)
This team grant is a collaborative effort, which experts in lymphoid cancer biomarkers and tumor microenvironment, hematology and cancer genomics jointly aim to understand and overcome treatment failure in lymphoid cancers. The team will identify and validate target-specific molecular tests characterizing genetic changes and molecular pathways which provide the preclinical rationale for novel drug development.

Large-Scale Applied Research Project (LSARP Program)
Dr. Steidl and Scott teams have successfully won a large-scale applied research project worth $11.9 million funded by Genome Canada, Genome BC, Canadian Institutes of Health Research and BC Cancer Foundation to study the genome biology of relapsed lymphoid cancers. Our large-scale, pan-Canadian study was launched last year to discover novel, actionable markers of relapsed lymphoma from which clinically relevant assays can be developed. This study also aims to implement genomic-based clinical tests, which have been previously developed by our research team, in the publicly funded health care system across the country to enhance more patient centric approaches and improve outcomes for lymphoma patients.