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Research Week 2019

Associate Professor at the Department of Internal Diseases, in the Faculty of Medicine, at Rīga Stradiņš University and Head of the Department of Endocrinology at Riga East Clinical University Hospital, endocrinologist Ilze Konrāde's daily life consists of treating patients in the hospital, working in the health centre, educating the physicians-in-training and supervising their research papers, as well as doing research of her own that is closely related to her clinical work in the hospital.

The professor researches late complications of diabetes mellitus, the identification and potential prevention of cardiovascular risk factors, thyroid autoimmunity, the provision for sufficient supply of iodine to the population, etc. Her most recent study, that will continue for the next two years, deals with the influence of the interaction between environmental and genetic factors on the development of autoimmune thyroid disorders. The Latvian Council of Science has granted 199 998 euro for this project.

Ilze Konrāde is not only the initiator and head of this project, but she also works with patient blood samples, because she "likes to use the pipette", and she is delegating more work to PhD students and residents because the most important thing is to understand the science "down to microlitres".

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As a child, did you know that you would like to be a physician?

Both yes and no. My father worked in the Department of Sports at the Riga Medical Institute (now: RSU) and I had been spending my summers in the "Taurene" athletes camp since the age of three. I was always surrounded by students there – prospective physicians. So, I naturally thought that I'd become one of them some day.

But it was not like I wanted to treat dogs and cats as a child. What has always attracted me to medicine was the need to help and answer difficult questions.

Why did you choose to specialise in endocrinology during your studies at the Medical Academy of Latvia (now: RSU)?

It became clear to me quite early. I think one of the most important things is to understand your own temperament and recognise your strengths and weaknesses. For example, I overreact in stress situations, so I can be neither a surgeon, nor a reanimatologist. I also couldn't be a surgeon because my classmates knitted my mittens for me (laughs). But I've always enjoyed deep analysing. Therefore, I enjoyed and couldn't choose between two disciplines – endocrinology and haematology.

It turned out, even as a student I started to work with children who had diabetes mellitus at summer camps. And I enjoyed it. Additionally, thanks to my knowledge of foreign languages, I had the opportunity to undertake a two-week internship in Hamburg (Germany) as a resident, where I had diabetes training – training as it should be, because a person who has a chronic disease has to learn how to adapt their insulin doses to various situations and to achieve their life goals.

A fantastic example is British Prime Minister Theresa May, who has diabetes and who talks about it openly. In an interview, when a journalist asked: "How do you manage with your diabetes?", she bravely answered: "As anyone else, just with four doses of insulin per day". There are outstanding athletes, who inject insulin. To make the patient take responsibility for his own disease, it's not enough to just provide knowledge, one must have the ability to motivate and to support, which greatly helps in working with students. 

That's how I started my work in endocrinology and I've never regretted it.

Not all physicians conduct research. How did you end up as a researcher?

There often are situations in endocrinology, as in all medical specialities, when everything appears too be clear, but something still doesn't fit or is different from what is written in the professional literature. And that's when I want to find out, why my case is different. That's exactly when I get ideas about what I should do and how I should treat this, and I want to research that. This happened to me with my first area of research.

Diabetes mellitus means that a person has an increased blood sugar level for a short or long period. Theoretically, the higher the permanent sugar level, the more, so-called, late complications he may encounter. This is the problem of diabetes, not merely a high blood sugar level, because glucose causes changes and damages the small blood vessels in the eyes, kidneys, feet, etc.; these changes are called diabetes complications. At that point the patient experiences deterioration in their quality of life and work capacity. However, life is not fair – sometimes a patient has many complications, even though he is controlling the diabetes well, and there are cases of bad diabetes control, when a patient has no complications. Therefore, it was important to find out why this happens.

Thanks to University of Latvia Professor Valdis Pīrāgs, who offered me work as a researcher at the University of Heidelberg (Germany), I joined a fantastic group of researchers, where I started using a pipette for the first time and started to learn everything that molecular biologists do. We studied the mechanism that people have, to a great extent, encoded in their genome – their natural ability to resist a high glucose level. It's a kind of medical pro et contra ("for and against") – to stimulate the organism with countless antioxidants or force it to activate its resources.

The group of researchers from the University of Heidelberg came up with an idea that resulted in a study and a high level scientific publication in "Nature Medicine". In that study we proved that the innate ability to resist a high sugar level is important in the development of pain in people who have diabetic neuropathy.

One person can't do all the work for a good scientific study and paper. Therefore, this group of researchers grew to be over 30 people. They are continuing this work in Germany, and I am researching something else.

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What are your current scientific interests?

When I returned to Latvia, I had a fantastic opportunity to participate in the work of the Laboratory of Pharmaceutical Pharmacology, led by RSU Professor Maija Dambrova in the Latvian Institute of Organic Synthesis. We continued to study the same thing that I had started in Germany. Then we started to focus more on the research of gut microbiota products, because, currently, many diseases are associated with changes in microbiota, i.e., the microbiota is disbalanced, therefore the intestinal wall permeability is increased and the microbiota influence absorption of certain substances from the intestines, directly aggravating metabolic and autoimmune disorders. So, in the Laboratory of Pharmaceutical Pharmacology, we studied how the diet of diabetes mellitus patients substantially increases the concentration of cardiovascular disease marker trimethylamine N-oxyde, and we were one of the first to prove that diabetes patients have a higher concentration of this substance (that is produced from, for example, meat and eggs by the gut microbiota) than those who have no diabetes.

For several years in Latvia, we have been studying the provision of access to iodine supply to women and children. Iodine is of great importance in pregnancy, because it affects the development of the nervous system. Although, overall, the provision of iodine in Latvia is relatively satisfactory, it is catastrophically low in pregnant women. However, good science teaches not only how to rapidly prevent risk, but also how to think through the consequences of overly active strategies. If suddenly all the salt in the shops were to contain iodine, the risk of autoimmune thyroid disorders would increase. And that got me interested in autoimmune thyroid disorders, which are quite prevalent. According to our data, antithyroid antibodies have been diagnosed in approximately 11% of women of reproductive age. Therefore, we applied for the Fundamental and Practical Project Selection by the Latvian Council of Science. Although genetics play a major role in the development of these diseases, they are triggered by environmental factors. How to modify them, which factors deserve more attention (stress, selenium, use of estrogens or smoking) – these are the questions that are topical globally. I think this was the reason for the good rating of our project by the reviewers. Now, we have to demonstrate that we can study these problems in RSU just as well as in England or Germany.

Would it be possible to do research work if you were not working in the hospital?

All of the patients with rare diseases, different complications and manifestations end up here, in Riga East Clinical University Hospital "Gaiļezers". These patients contribute to science, because we describe each of these medically interesting cases and talk about them in seminars, conferences, etc.

Regarding research work in Latvia, I want to emphasise the advantages, and one of them is effective cooperation. We have a long history of fantastic interaction and effective cooperation with scientific laboratories, for example, the Latvian Institute of Organic Synthesis laboratories, Latvian Biomedical Research and Study Centre, RSU Scientific Laboratory of Molecular Genetics, etc.

It's like a cooperation network that works in various directions. For example, I often get ideas for my own potential research from presentations by my colleagues in scientific congresses. So, I have an idea and patients, but the scientific laboratory can measure markers, etc. It can be also the other way around, when laboratory researchers hear an idea in a conference, we discuss and contribute to each other's ideas. Ideas develop, leading to new discoveries. For example, Fredric Bunting, who discovered insulin, got the idea for the synthesising of insulin after reading an article in the American Journal of Pathology.

So, participation in conferences, reading articles and clinical challenges in the hospital bring about scientific ideas. Then, a physician-researcher immediately figures out the potential collaborators in Latvia to implement one of these ideas.

Even the most brilliant ideas aren't worth anything, if we keep them to ourselves. They should be published! So, we begin with an idea, and the result should be a publication. In a perfect scenario, it's an international publication.

How many researchers are involved in the new project "The interaction of environmental and genetic factors in the immunopathogenesis of autoimmune thyroid disorders"?

There are quite a few of us from RSU. My role as project manager is to elicit curiosity about the problem to be researched in other departments and laboratories. Professor Aivars Lejnieks, Director of the RSU Department of Internal Diseases, has agreed to help with managing the project team. Other participants are Professor Andrejs Šķesters, lead researcher and manager of the RSU Scientific Laboratory of Biochemistry, lecturer Gita Gersone (ex. Krieviņa) from the RSU Department of Human Physiology and Biochemistry, Asoc. Professor Ieva Strēle from the RSU Department of Public Health and Epidemiology, as well as my brilliant PhD students Ieva Kalera and Tatjana Zaķe and resident Sabīne Upmale. They believed in this idea and have joined the study.

Laboratory of the Latvian Biomedical Research and Study Centre led by Associate Professor Jānis Kloviņš has agreed to do one third of the project. They will perform genetic tests for the genes affecting immunity, thyroid gland and selenium levels. The next step will be analysing the correlation between the results of the genetic tests and the environmental factors and clinical data.

I have heard a joke from a few of my foreign colleagues, who are editors of scientific magazines, that, after you get a scientific idea, you need to write a manuscript and it helps to put the problem in focus. Currently, while writing the project, we have done exactly that.

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Do you feel appreciated as a researcher?

I don't think like that! Money is required for reagents and the process, but I don't allocate a lot of money for salaries. Anyway, it ensures something that is hard to obtain otherwise. Most importantly, I like to present our study poster abroad and see that our idea is great, even if we hadn't always had access to the most advanced equipment or sufficient funds. I like the feeling of being the pioneer even in that little area and of the research process itself! Research is like a drug to me.

What is most difficult about research?

Of course, it's hard to realise that what you've been doing for a year was all for nothing. My path to an international publication in Germany involved millions of mistakes. I started in a new field, and, at first, I needed to understand what is right; however, no one had the right answer...

Not everything works out in research. There might be a conceptual or an analytical problem, when you're doing or measuring something incorrectly, the material might be of the wrong type and so the result is not valuable. I think that a failed idea journal might be useful in medicine. It could be used for publishing failures, i.e., failed hypotheses, so that no one else would do something like that again and wouldn't waste their time. (Laughs)

Do you think that anyone can be a researcher?

I think that almost anyone can be a researcher. One just needs to find what is interesting to them and suitable for their way of thinking.

It's good that we assign the RSU students to study something, as well, because it's a challenge that allows the young people to "get their act together" and expand their horizons. It allows them to read scientific publications with greater understanding.

Could the RSU International Scientific Conference that is going to take place in April 2019 be considered as a challenge and a chance to expand one's horizons?

Every researcher must pay attention to what others are doing and have accomplished, and not just in his own field, because otherwise he might miss a miracle... According to Latvian writer Rūdolfs Blaumanis, "The one who will follow the path honestly, will not go astray, but who will notify this kind of person about the wonders that dwell in the thicket?" It's the same with science – you can take your narrow path in medicine, but then you may often not notice what is in the thicket..

Conferences are needed, especially for specialists-in-training! Students usually prepare for classes to answer questions, which mostly are clinical. It means that they learn what is in the book. But each scientific conference encourages a new way of looking at things and broader ideas. Each congress or conference invites ideas, which you might, for example, collaborate on with someone who is studying something similar, by joining your forces.

How are you going to take part in the RSU Scientific Conference?

On 3 April 2019, Professor Aivars Lejnieks and I are going to supervise the section "The principle of complementarity in the research of metabolic diseases". As the title suggests, the work of the section will be associated with the fact, that, if you strive for excellence in science, you can't work alone, you need collaboration.

In this section, I have included topics and invited those institutions and researchers that I have had the most successful collaboration with in the research of metabolic diseases. These are the Latvian Institute of Organic Synthesis and Prof. Maija Dambrova, who I've mentioned previously. The Latvian Biomedical Research and Study Centre will talk about microbiota. Other participants will be the Scientific Laboratory of Molecular Genetics and its director Linda Gailīte, as well as the director of the Laboratory of Hygiene and Occupational Diseases and lecturer Inese Mārtiņsone.

What are your most significant scientific achievements?

I always emphasise to students that science can't exist for its own sake. Science is the contribution of your studies to the particular field, even if the contribution is small. Science is what you have proven and what was not known before.

So, the greatest satisfaction that I have is for the first article that was about the role of iodine, that we (i.e., our team of researchers) published in the Journal of the American Thyroid Association in 2012. It was a very independent project, fantastic collaboration with other RSU departments and the Latvian Institute of Organic Synthesis. Additionally, I like projects that students, i.e., prospective colleagues, take part in, because then they are infected with this sense of satisfaction about meaningful research. They still remember the passionate process of this project and the team spirit that brought us together, when we glued the boxes for the schools, listened to music, told jokes and various stories. It was one of the greatest projects!

A few more facts about Associate Professor Ilze Konrāde

  • 1996 - graduated from the Medical Academy of Latvia with Honours
  • 2008 - acquired a doctoral degree in internal medicine (doctoral thesis: "The role of the advanced glycation end-product receptor and glyoxalase-1 in the development of late complications of diabetes")
  • Since 1998 - working at Riga East Clinical University Hospital "Gaiļezers"
  • Since 2015 – lecturer in the Department of Internal Diseases at the RSU Faculty of Medicine
  • Since 2007 – member of the board of the Latvian Association of Endocrinologists
  • Since 2009 – chair of the board of the Latvian Association of Endocrinologists
  • Since 2016 – head of the Latvian Council of Science Expert Committee for Biology and Medical Science
  • Co-author of several books and booklets

  • Author and co-author of 59 publications