University of Toronto-Mount Sinai Hospital Genetic Research Center

Mark Silverberg, MD, PhD, FRCPC

Principal Investigator

Professor of Medicine, University of Toronto

Gastroenterologist, Department of Medicine

Senior Investigator, Lunenfeld-Tanenbaum Research Institute Inflammatory Bowel Disease Group

Co-investigators

  • Ken Croitoru, MD, Professor of Medicine, University of Toronto, Gastroenterologist, Mount Sinai Hospital/Sinai Health System
  • David Guttman, PhD, Professor, University of Toronto, Ecology & Evolutionary Biology, Director, University of Toronto Centre for the Analysis of Genome Evolution & Function (CAGEF)
  • Mathieu Lupien, PhD, Senior Scientist, Princess Margaret Cancer Centre/OICR, Associate Professor, Dept. of Medical Biophysics, University of Toronto
  • Daniel De Carvalho, PhD, Scientist, Princess Margaret Cancer Centre/OICR, Assistant Professor, Dept. of Medical Biophysics, University of Toronto

Clinical Collaborators

  • Hillary Steinhart MD
  • Adam Weizman MD
  • Geoffrey Nguyen MD, PhD
  • Vivian Huang MD
  • Zane Gallinger MD
  • Laura Targownik MD

Advanced IBD Fellows

  • Cristian Hernandez MD
  • Margaret Walshe MD
  • Karen Boland, MD PhD
  • Samuel Truniger MD

Lab and Project Management

  • Joanne Stempak MSc
  • Melissa Filice MSc

Elucidating Pathophysiological Mechanisms of Intestinal Inflammation. Parent Grant 2017-2022

Specific Aims:

Aim 1) Identify gene expression profiles and pathways that will aid in understanding the mechanisms of UC relapse and prediction of UC relapse and their regulation by miRNAs and chromatin accessibility. This will be accomplished by measuring gene expression, miRNA and chromatic accessibility profiles in the colonic tissue of UC subjects immediately prior to the onset of inflammation relative to baseline measurements.

Aim 2) Identify intestinal microbes and microbial function that precede UC relapse. This will be accomplished by determining the composition of the microbial flora adherent to the intestinal tissue as well as that of stool.

Aim 3) Continue to support the mutually agreed upon Consortium-wide studies involving elucidating the factors contributing to relapse of inflammation following surgery in CD subjects, completing the discovery of all genetic variation associated with IBD, advancing our knowledge of the functional biology of such genetic variation and to utilize these data to bring clinically meaningful tools into use to promote improved outcomes for individuals affected by IBD. These will be accomplished by patient recruitment and by bringing our significant clinical and scientific expertise to the IBDGC.

Impact of an anti-inflammatory diet on disease activity and microbiome composition in active UC. Administrative Supplement

Specific Aims:

Aim 1) Elucidate the effects of diet on the microbiome community

Aim 2) Determine if inflammation and disease activity are affected by diet and its relationship to the microbial structure and function

Additional resources of value Mount Sinai Hospital/University of Toronto

Toronto local ileal CD recurrence cohort: The NIDDK Consortium-wide project focusing on genomic and microbial mechanisms of post-operative Crohn’s disease recurrence evolved out of a local Crohn’s and Colitis Canada grant received by the PI (Silverberg). An additional 45 subjects from the local study have been contributed to the overall Consortium project.

Prospective Pelvic Pouch Study cohort: A local Crohn’s and Colitis Canada funded study to understand the genomic and microbial factors that lead to new onset ileal inflammation in a pelvic pouch after colectomy in UC

GEM Cohort: Collaborator and co-investigator on the largest study world-wide to identify predictors and mechanisms of new onset CD in a genetically susceptible population of first-degree relatives of patients with CD (PI: Croitoru)


Major interests:

  • Clinical and molecular classification of inflammatory bowel disease
  • IBD therapeutics
  • Multi-omic profiling of tissue from IBD patients to better understand genomic and microbial mechanisms of IBD onset, relapse and recurrence in human models of IBD (post-op CD, UC relapse, pouchitis)