Associate Professor, Departments of Pathology & Laboratory Medicine, Paediatrics; Associate Lab Director, Tissue Typing Laboratory and Molecular Hematology Laboratory, CLS; Barb Ibbotson Chair in Paediatric Haematology
Currently accepting PhD/Master students. Outstanding students are welcome to apply for studies under my supervision toward PhD, Master’s degree. First year BHSC students interested in a project or summer studentship under my supervision are also encouraged to apply. Applications should be in the form of an email explaining why you are interested; Resume/Curriculum Vitae should be attached.
Room 269 HMRB
3330 Hospital Drive, NW
Calgary, AB T2N 4N1
Primary Research Interest:
Transplant Immunology: Immunogenetic biomarkers for pathogenesis and therapy of complications of hematopoietic cell and renal transplantation
Killer Immunoglobulin like Receptor and immunoregulation of NK cells; HLA and pharmacogenetics
1. Immunogenetic Biomarkers for pathogenesis and therapy of complications of hematopoietic cell transplantation (HCT).
HCT is a lifesaving treatment that frequently cures patients with hematologic malignancies and non-malignant diseases like aplastic anemia, thalassemia or congential immune deficiency. Despite optimal supportive care and high standards of tissue typing investigations, complications such as graft-versus-host disease (GVHD), disease relapse, posttransplant infections and second malignancies remain major limitations. The research theme#1 of my laboratory is to identify immunogenetic biomarkers that regulate immune mediators, surface receptors and host defence molecules and influence the risk of these complications. We are currently focussing on:
(i) Killer Immunoglobulin like Receptors (KIRs): Human NK cells form the first line of defense against infections and tumors and are the first lymphocytes that reconstitute to normal levels in the peripheral blood after HCT. The functioning of NK cells is governed by specialized receptors – KIRs that exists in activating and inhibitory forms. My current research interest is to understand the impact of diversity and expression of KIR genes on the recovery and functions of NK cells after HCT and its influence on the risk of GVHD, disease relapse and poststranplant infections.
(ii) Cytokine gene promoter polymorphism: Cytokines act as chief mediators/regulators of immune response, inflammation and host defence. Genetic control of cytokine production is evidenced by polymorphisms in cytokine gene regulatory regions that produce low, moderate, or high cytokine expression profiles. My research group is interested in assessing whether a cytokine gene mismatched HCT (for example a transplant between high cytokine producing donor and low cytokine producing recipient) leads to a change in cytokine production profile of the transplant recipient and thereby manipulates transplant outcome.
(iii) Genomic instability as a biomarker for posttransplant malignancies. HCT recipients have 2 to 4-fold higher likelihood of developing a solid cancer compared to the general population. However, cancers of some organs are frequent (eg, skin, mouth, esophagus, thyroid, liver, bones, brain) whereas cancers of other organs are rare (eg, nasal mucosa, small intestine). My laboratory is interested in assessing whether genomic instability (a characteristically a precancerous or cancerous state) also occurs more frequently in epithelium frequently involved with cancer and whether pathogenesis of second malignancy after HCT is due to chronic inflammation (associated with chronic GVHD) leading to genomic instability and subsequent cancer.
2. Histocompatibility and Immunogenetic biomarkers for pathogenesis and therapy of complications of kidney transplantation.
Last two decades have witnessed a momentous decline in the incidence of acute kidney allograft rejection; however this success was not translated for the long-term attrition rate. Chronic Allograft Failure (CAF) is now the foremost cause of renal allograft failure. The research theme#2 of my laboratory is to identify histocompatibility and immunogenetic biomarkers that influence the risk of CAF. We are currently focussing on the presence of posttransplant antibodies against HLA class I and class II antigens and non-HLA antigens (eg, MICA), cytokine gene polymorphisms and recipient-KIR and donor-HLA mismatches.
3. Human Leukocyte Antigens and pharmacogenetics.
In addition to the strong genetic linkage of HLA class I and class II genes with autoimmune diseases, recently, even stronger HLA associations are reported in drug hypersensitivities to the reverse-transcriptase inhibitor Abacavir (HLA-B*5701), the gout prophylactic allopurinol (HLA-B58) and the antiepileptic carbamazepine (HLA-B*1502). The research theme#3 of my laboratory is to understand the mechanism of drug-induced hypersensitivity and the basis for its association with HLA alleles.
Other Area(s) of Research:
Killer Immunoglobulin-like Receptor and immunoregulation of NK cells; HLA and pharmacogenetics