​Inflammatory bowel diseases (IBD) are idiopathic, chronic intestinal disorders of complex pathogenesis and involve an aberrant immune response to some environmental antigen in genetically predisposed individuals. IBD includes both Crohn’s disease (CD), and ulcerative colitis (UC). Approximately 230,000 Canadians are affected by these diseases and they have important repercussions on quality of life and on both personal and societal direct and indirect costs. The cause(s) are poorly understood, and treatment is largely symptom-based and not curative. Commonly used drugs may have potentially important adverse effects such as cancer and serious infections. Moreover, some patients are resistant to these drugs. Therefore, safer and more efficient therapies are needed. Thus, new, effective and safer therapies are required. The primary mission of our laboratory is to develop novel therapeutic strategies in this field. Our research interests have mainly been in the areas of neuroinflammatory mechanisms and neuroendocrine peptides. I have extensive research training at world-renowned institutes, and at the University of Manitoba, building upon my expertise in gut neuro-inflammation, I will explore the role of neuroimmunoendocrine regulation during the development of gastrointestinal inflammation and will elucidate the mechanisms involved in the evolution of the gut maintaining its normal immune homeostasis to developing chronic gastrointestinal inflammatory disease.

Brain Gut Axis

Our goal is to further explore the brain-gut axis and define more precisely the gut immunologic response during the development of depressive-like behaviour. We are also exploring the implication of the vagus nerve and post-traumatic disorders in the context of colitis. The goal of this innovative and high impact study is to demonstrate that the widespread use and potential impact of neural modulation (e.g. use of anti-depressant and pharmacological stimulation of the vagus nerve) may be important therapeutic adjuncts to the conventional approach in IBD.

Principal Collaborator
Prof Bernstein
University of Manitoba
​Prof Khan
McMaster University, Hamilton
Prof. Gilbert Kirouac
University of Manitoba

Funding Agencies

Enteric Nervous System Axis

​The gastrointestinal tract is heavily controlled by locally distributed neurons in the enteric nervous system (ENS). These neurons control many functions, including generation of organized patterns of gut muscular activity that aids digestion. The human ENS contains 200 to 600 million neurons, which is more than in the spinal cord, thus indicating its in importance in the gastrointestinal system. Enteric neurons use many chemical neurotransmitters to communicate with each other. We have discovered that a specific class of enteric neurons also uses another more direct mode of communication that is mediated by electrical synapses formed by structures called gap junctions composed of the protein connexin36. Such synapses, found in the last decade in widespread areas in the brain, play critical roles in brain cognitive and motor functions. Our work has shown that gut contractile activity is abnormal in transgenic mouse models that lack the gene coding for connexin36. Electrical synapses formed by this protein are used by a specific population of enteric neurons called nitrergic neurons that have critical functional roles in the ENS. Using electrophysiological, whole gut imaging and cell biological approaches, we will define processes whereby electrical synapses contribute to the activity of these neurons, and the specific patterns of motor gut contractions that they govern. In addition, we will determine how these synapses influence and are influenced by inflammation in animal models of experimental colitis and in humans with inflammatory bowel disorders such as ulcerative colitis. The results of our studies will provide the basis for formulation of concepts on how electrical synaptic communication between enteric neurons contributes unique properties to the activity of neural circuitry that regulates gut physiology, which could lead to the development of improved therapeutic strategies in treating intestinal inflammatory diseases.

Principal Collaborator
Prof Bernstein
University of Manitoba
​Prof Khan
McMaster University, Hamilton
Prof. Jim Nagy
University of Manitoba

Funding Agencies

Neuro Endocrine Axis

The goal is to explore the use of chromogranin-A (CgA)-derived peptides as markers or as a therapeutic treatment in the prevention of chronic quiescent colitis, an approaches not present in or outside Canada. We anticipate this research will lead to the development of new diagnostic markers in IBD and possibly new treatments.

Principal collaborators
Prof Bernstein
University of Manitoba
​Prof Khan
McMaster University, Hamilton
Prof Metz-Boutigue
INSERM, Strasbourg, France

Funding Agencies

Neuro Immonological Axis

There is some indication that a group of molecules implicated in immune cell attraction named semaphorins can regulate inflammation in the gut. This study aims to determine how semaphorin can be harnessed to reduce intestinal inflammation and ultimately serve as a safe therapeutic target in IBD. Our studies will use clinical, physiological and molecular tools to identify how a specific semaphorin, semaphorin3E is involved in targeting an antigen presenting cells called dendritic cells, in the inflammatory bowel disease states in humans and animal models.We will explore a new pathway implicated these cells response during intestinal inflammation that will provide a basis for possible new treatments of IBD. Semaphorin 3E (Sema3E) has emerged as an new essential axis involved in the dendritic cell immunoinflammatory response; however, the role of Sema3E in IBD is unknown. We are exploring its role in the context of chronic quiescent colitis and in IBD. Our recent data demonstrated that Sema3E could be a protein of interest in developing new treatments for patients with IBD. 

Principal collaborators
Prof Bernstein
University of Manitoba
​Prof Khan
McMaster University, Hamilton
Prof Soussi-Gounni
University of Manitoba

Funding Agencies