Investigator Spotlight: October 2014
Marika Bogdani, MD, PhD
Dr. Bogdani is a research scientist, working with Dr. Thomas Wight at the Benoroya Research Institute.
- Tell us about your education and background – where are you from, where did you go to school?
I grew up in Tirana, Albania, and studied medicine at the University of Tirana, where I graduated as MD and was honored with the University Medal. After specializing in pathology and working several years as clinician, I completed with honors the Master program in Medical and Pharmaceutical Research at the Free University of Brussels (VUB) and then the doctoral thesis at the department of Experimental Pathology, Diabetes Research Center in Brussels (VUB). My PhD work resulted in two publications; one of them was rewarded the “Best paper” in Diabetologia journal in the basic research category in the year of publication, and for the other one I received a prize from Sanofi-Aventis.
- Where do you currently work and what is your position? What does a “day in the life” look like for you?
I am a research scientist in the Matrix Biology Program at the Benaroya Research Institute in Seattle. I am part of a team interested in the importance of the extracellular matrix in autoimmune diseases. My usual work day is filled with research project-related work, as well as discussions with my colleagues and collaborators. Part of the work is also dedicated to manuscript preparation and grant writing. I regularly attend the scientific meetings related to the basic, clinical and translational research at the Benaroya Research Institute and at the University of Washington. The Benaroya Research Institute offers a highly collaborative and stimulating scientific environment, and it is a pleasure to work every day with great scientists with a positive and innovative attitude, which allows for a creative work and sharing of ideas.
- Why diabetes? How did you get involved in diabetes and/or what made you want to work in diabetes research?
When I was pursuing the Master program in Brussels, I had the opportunity to join the department of Experimental Pathology at the VUB. This department was founded by Prof. Willy Gepts, an excellent pathologist renowned for the description of the pathology of the endocrine pancreas in human diabetes. Colleagues of Prof. Gepts in the department of Experimental Pathology with whom I worked closely have also made significant contributions to the advancement of type 1 diabetes research. While working on my Master thesis, I became familiar with the diabetes research projects that were going on at the Diabetes Research Center at the VUB. I worked closely with excellent scientists in an environment that was scientifically demanding, and which, at the same time, provided all the means necessary to perform innovative scientific work. My interest in understanding the underlying mechanisms of tissue pathological changes in human diseases along with the outstanding scientific environment where I trained helped channel my future interests in the field of diabetes.
- Tell us about your research.
Although significant progress has been made in the type 1 diabetes research to find a cure for the disease, we still need to better understand the processes that lead to the damage of the pancreatic beta cells. In this regard, the role of the extracellular matrix in type 1 diabetes pathogenesis is largely unknown. The overall purpose of my research is to understand how changes in the extracellular matrix affect insulitis initiation, progression and beta cell destruction in diabetes. Type 1 diabetes results from an attack by inflammatory cells on the insulin-producing beta cells in the pancreas. Aggregates of inflammatory cells surrounding and invading the islet are referred to as “insulitis”. Although the triggering mechanism of type 1 diabetes is still not clear, the entire process must rely on the migration of inflammatory cells from the blood stream into the pancreatic islets via interaction with the extracellular matrix that lies between islet capillaries and endocrine cells. The extracellular matrix was originally viewed as an inert structural component of human tissues, providing strength, form and elasticity, but recently has been found to play an important role in regulating different cellular responses.
Our research focuses on a specific extracellular matrix molecule, hyaluronan, a long chain glycosaminoglycan distributed widely throughout different tissues. Hyaluronan is highly abundant in inflamed tissues and its synthesis is responsible for many of the tissue changes associated with inflammation, including vascular permeability changes and adhesion, activation, and migration of immune cells at the sites of injury. Hyaluronan exerts these effects through interactions and formation of macromolecular complexes with hyaluronan-binding molecules called hyaladherins, such as inter-α-inhibitor, versican and tumor necrosis factor-stimulated gene-6.
We have made the novel observations that hyaluronan and hyaladherins increase in pancreatic islets of younger donors and accumulate in regions of lymphocytic infiltrates in type 1 diabetes, and that both the amount and distribution of these specific extracellular matrix molecules vary with time since the onset of diabetes. We have also shown that hyaluronan and hyaladherins are deposited in the follicular germinal centers and T-cell areas, regions of immune cell activation, in both human pancreatic lymph nodes and spleen in type 1 diabetes. These findings are important since they implicate specific extracellular matrix components in the pathogenesis of type 1 diabetes and point to a previously unrecognized characteristic of tissues involved in the pathogenesis of this disease.
We are investigating the regulation of hyaluronan accumulation in pancreatic islets and lymphoid tissue in type 1 diabetes, the functional significance of hyaluronan – hyaladherin complexes in initiation and progression of insulitis, and the role of these complexes in modulation of immune cell interactions and immune cell phenotype.
Investigating how hyaluronan complexes affect islet inflammation is a novel area of research. This represents an exciting and new way of looking at the process of pancreatic beta cell destruction. My training as MD, as pathologist and as researcher in beta cell therapy, and my focus on the importance of the extracellular matrix in health and disease give me belief that our research will lead to new and important insights into the pathogenesis of type 1 diabetes, and potentially to generation of novel, transformative therapeutic strategies to prevent the development of this disease.
- What are your thoughts on the progress being made in T1D research as a whole?Over the years, remarkable advances in scientific knowledge have been made in the major areas of type 1 diabetes research including treatment, prevention and improving the quality of care of people with diabetes. Although a cure for type 1 diabetes is not yet available, significant progress has been made in understanding disease pathogenesis and possible mechanisms leading to beta cell death, elucidating the genetic predisposition to the disease, identifying markers to monitor progression to diabetes, and in designing protocols for immune intervention and prevention trials aiming at modulating the immune response and preservation of the beta cell mass. Considerable advancements have also been made in the field of beta cell therapy with increased understanding of beta cell development and regeneration from different cellular sources, and in clinical islet and pancreas transplantation. The design of artificial pancreas device systems and glucose modulating agents has led to significant advances in glucose monitoring and insulin therapy. These remarkable advances made in type 1 diabetes research have been demonstrated to be efficacious in significantly improving the quality of life of diabetic patients.
- Why is diabetes research so important?
Diabetes is one of the most important medical problems of our time. As a life-long condition that affects millions of people worldwide and in particular children and young individuals, it is a psychological and financial burden to the affected families and to society. Recognition of the impact of diabetes, particularly juvenile diabetes, on the patients and their families’ lives, motivates us to advance our understanding of why and how the pancreatic cells are destroyed in type 1 diabetes, which would lead to the design of therapies to prevent the disease in those at risk and ultimately find a cure for diabetic patients. It is through research that we can pursue and achieve these goals.
- Do you have anything extra you would like to share? Is there anyone to thank or acknowledge?
I have had the great opportunity to have excellent mentors, renowned in the fields of type 1 diabetes research, both for my PhD at the Diabetes Research Center (VUB) in Brussels and post-doctoral training at the Department of Medicine at the University of Washington in Seattle. I am fortunate to work closely with first-rate scientists in the fields of extracellular matrix biology and immunology at the Benaroya Research Institute. Working with them has cultivated my scientific curiosity and has sharpened my thinking as scientist. I am also thankful to all the highly professional lab members in those centers, whose assistance has helped accomplish my work.
I would like to thank all those who have contributed and continue to contribute to the advances in diabetes research. Their trust and confidence in scientific research, and their dedication to help in any way they can are precious. In particular I would like to thank the organ donors. Their altruistic donations not only save the lives of those at high mortality risk, but also aid research to advance understanding of disease pathogenesis which would lead to discovery of cures and remedies to ensure better health for everyone.
I would like to acknowledge the great support from JDRF, which is dedicated to discover and develop therapies to improve life with type 1 diabetes. The continuous support of funding organizations led by JDRF, especially in areas such as the importance of the extracellular matrix in the pathogenesis of type 1 diabetes, is critical and indispensable to our efforts to find better treatments, a means of prevention, and, ultimately, a cure.
When you’re not working, what do you like to do for fun?
I like reading, cooking and classical music concerts. I enjoy very much long walks with my family, for which Seattle offers many beautiful areas, and we also spend time with our friends as often as possible.