An overarching theme of my laboratory's work is the experimental investigation of the network behavior of biological systems relevant to human disease using a variety of biochemical, biophysical, molecular biological and systems modeling approaches. A primary focus is the biology of solid tumours such as colorectal cancers.
Michael H. A. Roehrl
- Proteomic Biomarker DiscoveryWe use a variety of biochemical tools including high-resolution mass spectrometry for the characterization of proteome-level alterations in primary human tissue samples. Using this approach, we have discovered a variety of novel proteins and pathways in both colorectal cancers and lung adenocarcinomas.
We are refining these approaches to investigate posttranslational modification events directly in primary samples (e.g., phosphorylation or glycosylation events) using novel chemical affinity enrichment strategies as well as metabolic labeling strategies.
Using similar experimental approaches, we have expanded our work to serum samples with the goal of defining the totality of antibody specificities in a patient's serum, what we call the autoantigen-ome. We are now examining the temporal proteomic evolution of the autoantigen-ome in patients with cancers and autoimmune diseases such as lupus. We expect that this will lead to the discovery of novel antigenic epitopes that can be used for both diagnostic and therapeutic purposes.
- The Impact of Genomic Aberrations on the ProteomeWith near-complete genome sequencing of cancer samples it becomes feasible to use this information (together with transcriptome-wide expression data) to try to answer some fundamental questions about proteome-level effects. For example, we would like to answer the question of how many of the dozens of somatic coding sequence changes at cancer genome level actually make it into detectable aberrant proteins as opposed to leading to unstable mRNA, abortive translation events or unstable proteins with accelerated turnover. This is an important question because all current targeted therapies are directed against proteins (enzymes or structural proteins), and therapeutic effects will only be experienced when the modified protein is made.
To this end, we are sequencing a variety of cancer tissue samples for which we also have high-quality fresh-frozen samples from the very same patient and tumour location. This allows us to inform mass spectrometric investigation with prior knowledge about sequence-predicted, patient-specific alterations and to focus on the direct detection of mutated proteins and peptides.
Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids.
Nat Med. 2015 Oct 26;
Cancer Immunol Res. 2015 Sep 29;
Biopreserv Biobank. 2013 Apr;11(2):83-93
J Pathol. 2014 Jan;232(2):199-209
Infectivity, transmission, and pathology of human-isolated H7N9 influenza virus in ferrets and pigs.
Science. 2013 Jul 12;341(6142):183-6
Gastrointest Endosc. 2012 Aug;76(2):421-2
Capillary hemangioma of the esophagus in a patient with systemic sclerosis and gastric antral vascular ectasia.
Gastrointest Endosc. 2012 Aug;76(2):418-9
Crystallization and preliminary crystallographic study of a trypsin-resistant catalytic domain of human calcineurin.
Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012 May 1;68(Pt 5):574-9
Computed tomography of granulomatous pneumonia with oxalosis in an American alligator (Alligator mississippiensis) associated with Metarhizium anisopliae var anisopliae.
J Zoo Wildl Med. 2011 Dec;42(4):700-8
Arch Pathol Lab Med. 2011 Nov;135(11):1499-503
Scientist, Princess Margaret Cancer Centre
Director, UHN Program in BioSpecimen Sciences
Department of Laboratory Medicine and Pathobiology, University of Toronto
Department of Medical Biophysics, University of Toronto
Associate Member, Ontario Institute for Cancer Research (OICR)