Ramin Kholdebarin

Background:

Ramin completed a Bachelor of Science in biochemistry at the University of British Columbia. He went on to study medicine at Queen’s University, where he developed an interest in clinical research. Through the support of research scholarships from Queen’s University, Ramin pursued summer research projects at the University of Toronto. These efforts led to publications titled “Risk Factors for Bile Duct Injury During Laparoscopic Cholecystectomy” and “Multicenter Study of Compliance and Drop Administration in Glaucoma”.

As a resident in general surgery at the University of Manitoba, Ramin continued his interest in clinical research by studying the effects of a newly formed Acute Care Surgery Service on surgeon quality of life and resident education. While pursuing further research opportunities during residency, Ramin met Dr. Richard Keijzer, a paediatric surgeon with an interest in translational research. Dr. Keijzer is trying to understand the pathophysiology of congenital diaphragmatic hernia and how it leads to pulmonary hypoplasia. Ramin completed a Master’s of Science in surgery under the supervision of Dr. Keijzer. Ramin’s research has led to multiple publications in peer reviewed journals and presentations at national conferences including Canadian Surgery Forum, Canadian Association of Paediatric Surgeons and Canadian Society of Surgical Oncology.

Research Summary:

Congenital diaphragmatic hernia (CDH) is a developmental defect in the diaphragm that leads to herniation of abdominal viscera into the chest cavity. Children born with this condition have small lungs (pulmonary hypoplasia), which is a source of major morbidity and mortality. The pathophysiology of pulmonary hypoplasia is poorly understood and the majority of cases do not have a genetic predisposition. Dr. Keijzer has studied microRNA expression in CDH lungs from humans and found increased expression of miR-200b. To further study the role of miR-200b in lung development, we developed a technique for mapping microRNA expression in tissues from a rat model of CDH and surprisingly found decreased expression of miR-200b.

This conundrum was solved when we looked at miR-200b expression in response to Fetoscopic tracheal occlusion (FETO) therapy in utero. FETO ameliorates pulmonary hypoplasia by preventing egress of fluid out of the lungs during embryonic development. miR-200b expression was increased in response to therapy and miR-200b levels could predict survival following treatment. Therefore, we concluded that miR-200b upregulation is a compensatory response to the deleterious effects of CDH. This response occurs naturally in human CDH and is further enhanced by intrauterine therapy. This finding also helped explain differences in the characteristics of pulmonary hypoplasia in humans vs. the rat model that have been known for some time. This project is a good example of how translational research, correlating clinical data to basic science research, can enhance our understanding of human diseases.