An Interview with Associate Professor Stavroula Kousteni (Part Three)

Author(s): Scott Douglas Jacobsen

Publication (Outlet/Website): In-Sight: Independent Interview-Based Journal

Publication Date (yyyy/mm/dd): 2016/08/22

Abstract

An interview with Associate Professor Stavroula Kousteni. She discusses: skeletal system as the endocrine system; glucose homeostasis; human symptoms similar to mice models; most appealing social philosophy; most appealing economic philosophy; bad science, pseudoscience, and non-science, or misinformation, with respect to medicine and improvement of the public discourse and knowledge of science; and concluding feelings and thoughts.

Keywords: economic philosophy, endocrine, science, skeleton, social philosophy, Stavroula Kousteni.

An Interview with Associate Professor Stavroula Kousteni: Associate Professor, Physiology and Cellular Biophysics, Columbia University (Part Three)^{[1],[2],[3],[4]}

*Footnotes throughout the interview, and bibliography and citation style listing after the interview.*

12. One implication is that the skeletal system is part of the endocrine system as well. 

This research theme is explored by the other half of my lab. This work was started by another investigator in the bone field, Dr. Gerard Karsenty. He was the first one that showed, back in 2007, that a hormone secreted specifically by osteoblasts called osteocalcin, improves glucose metabolism, and insulin production and sensitivity. In fact, his lab has done a lot of work to integrate bone into an endocrine system, which includes the pancreas and other glucose regulating organs such as the liver or adipose tissue.

My lab has tried to identify new hormones that are secreted by osteoblasts and regulate novel aspects of energy metabolism. We found one that regulates insulin secretion from the pancreas and appetite.  The function of bone as an endocrine organ that regulates whole body metabolism has now expanded to other unanticipated functions: such as male fertility and cognition.

13. When you state that it has serious implications for blood glucose, then that relates to the pancreas, the liver, fatty or adipose tissue, male fertility, and cognition, each of those areas has, at least, some relation to glucose metabolism. How does this relate to keeping blood glucose stable? In other words, blood glucose homeostasis among other things.

When we make mice that lack this hormone from the osteoblast, the mutant mice have higher blood glucose levels and lower insulin levels, than normal mice, a combination that is not good. (Laughs) If there is not enough insulin in the body, cells do not get a signal to import glucose. The mice become glucose intolerant because they do not metabolize glucose well. Also, when they eat or when they eat a high-fat diet, they gain more weight than they would if they did not lack the hormone. This metabolic abnormality shows that the hormone is required for glucose homeostasis.

14. When I think about it, it is early. Those reports were put out at the same time. There has been further research done.^[5] With that in mind, you have seen some of the other ‘correlations-of-action’, say, to the areas stated by you. Cognition, male fertility, adipose tissue, and so on, are there people that don’t have the gene or it’s not upregulated for them – and so they start to show symptoms similar to the mice?

Translation of mouse models into human systems is complex. To simplify, there are two ways to do it. One is through correlative studies. You have two groups of people. You have one group that is healthy. You say, “Okay, this one has a healthy level of these hormones.” I am going to measure the level of these hormones in both groups. What are the levels in normal people and diabetics?

Those studies are indicative, not mechanistic. This has been done for the osteocalcin work. Many studies show osteocalcin levels have an inverse correlation with glucose levels in humans. Higher osteocalcin levels correlate with insulin sensitivity. The second approach is by genetic means. You can search for mutations in the protein of interest by screening the DNA of a large population. If a mutation can be found, then we see if the people bearing the mutation have metabolic abnormalities.

Because hormones are important for homeostasis and for survival, it is uncommon to find mutations in them, presumably the body develops protective mechanisms to preclude them. Therefore, if the receptors through which the hormones work is known, we search for mutations in the receptor. The Karsenty group has done this for the osteocalcin receptor and found mutations in it that affect fertility in males.

15. What social philosophy most appeals to you?

In general, I believe in giving, if I could describe in one simple word for a lot of personal beliefs: giving. I consider myself lucky to be where I am and do what I love. I think that it is our responsibility – at least that’s how I view myself – to be citizens in a place where we are able to do what we want to do, to teach it, to pass it to other people, and to help them understand how to do it better.

To help in any way that we can in whatever area we are more sensitive to, especially in an area where we are more sensitive to; for example, my country, Greece, among other troubles lives through and deals firsthand with an immediate crisis. We’ve had thousands of refugees embarking on vessels of despair and too often losing their lives in efforts to escape to Greece. I am very sensitive to that. My 16-year old son and I belong to different organizations who actively try to help the immigrants.

I’m very sensitive to women’s issues. Women face very challenging and often rehabilitating issues in many different aspects that affect their personal and professional life, their physical and emotional wellbeing.  I am trying to understand this problem within the environment I work, and function and give/help to alleviate them as much as I can. That is my main philosophy, social philosophy, very simplified: give. Teach what you’re best at doing, inspire people to do it, and then help with what you’re more sensitive to. The world has many problems, but we’re all sensitive to it in different ways. Find that niche, find that area, and contribute to it.

16. What economic philosophy most appeals to you?

People should be rewarded for what they do and how much they try. Part of this is financial reward, but I don’t believe in exploiting it. I don’t believe in its extreme case.

17. There’s a lot of bad science, pseudoscience, and non-science with respect to medicine. Many citizens take these false medical services for fatal health problems and at times die without proper medical care. To solve this problem of public ignorance of science, cynical exploitation of the ignorance by non-scientists and non-medical professionals, and the demarcation of good medical care from bad medical care, what can be done?

I don’t know if you can call it bad science, but you can definitely call it misinformation. It is usually people without appropriate expertise who make wrong associations, the wrong correlations, and present them in the wide public. The only means to overcome this problem is with an abundance of the correct information. Means that scientific research can be translated into lay language for the public on the impact of the findings on their whole and not in partiality.

For example, we live in an era when certain patients can be offered the opportunity to have their genome sequenced looking for mutations that may help to more precisely characterize their disease and to in turn offer clues for how to treat it. This is the concept of Precision Medicine. That is, medicine tailored to address the personal needs of a patient.  Patients should be informed about it. They should understand the possibilities and limitations. The same approach should be followed to inform patients about new discoveries with clinical applications relevant to their disease, especially if such applications are available and easy to acquire.

Large medical institutions with substantial research where knowledge is actively shared and discussed daily tend to do that. Same with many scientific societies. For example, the American Society for Bone and Mineral Research has task forces whose role is to outreach its members and through this process raise awareness and update its medical membership on new guidelines and treatment options for bone and bone-related diseases.

Also, it provides free access to the public to an online Educational Research Center that has links to disease descriptions, recommendations for treatment, explanations of the disease, and links that take you to what is most recently known or published about it. There is a large research feed that one can go through. The American Society of Hematology is doing it the same things for a very large number of patients who suffer from different types of hematological diseases and malignancies.  In general, scientific societies are working to get the information to the patients in an easily and freely accessible manner.

18. Any feelings or thoughts in conclusion?

I think we have reached an era in terms of research and methodologies that we have amazing tools in our hands to ask important and difficult but better informed questions about the pathogenesis of many diseases that were thought of as incurable. Also, we have new tools and methods to target them. The face of research is changing too. It is extremely exciting too. In contrast to the past, if you did work that was quality and satisfying to work in and with your lab, you will see now that the most important discoveries and comprehensive works involve teams of investigators with a lot of different types of expertise.

They are cell biologists, mouse geneticists, human geneticists, biostatisticians, and so on. We live in a time that is both exciting and inspiring to see how many possibilities we have to think about the pathogenesis of disease. In a time that it is very important and crucial to work collaboratively to interrogate every problem from different perspectives, whether those involve samples from mice or humans, or cross-discipline expertise. If we keep doing it, I cannot wait to see how many discoveries we will reach in understanding disease pathogenesis and how much we can do it treating them. I live in this time. It is an exciting time to live in.

Thank you for your time, Professor Kousteni.

Bibliography

1. Columbia University. (2016). Kousteni, Stavroula, Ph.D. Retrieved from http://www.physiology.columbia.edu/Stavroula.html.
2. Columbia University Medical Center. (2014, January 21). Common Blood Cancer May Be Initiated by Single Mutation in Bone Cells. Retrieved from http://newsroom.cumc.columbia.edu/blog/2014/01/21/common-blood-cancer-may-initiated-single-mutation-bone-cells/.
3. Columbia University Medical Center. (2014, January 22). Potential Drug Target Found for Common Blood Cancer. Retrieved from http://www.dddmag.com/news/2014/01/potential-drug-target-found-common-blood-cancer.
4. News-Medical.Net. (2014, January 21). Mutation in bone cells may cause acute myeloid leukemia: Study. Retrieved from http://www.news-medical.net/news/20140121/Mutation-in-bone-cells-may-cause-acute-myeloid-leukemia-Study.aspx.
5. Waknine, Y. (2014, January 27). Hit the Cancer Where It Lives: A New Approach to Treating AML. Retrieved from http://www.medscape.com/viewarticle/819764.

Appendix I: Footnotes

[1] Associate Professor, Physiology and Cellular Biophysics, Columbia University.

[2] Individual Publication Date: August, 22 2016 at www.in-sightjournal.com; Full Issue Publication Date: September 1, 2016 at https://in-sightjournal.com/insight-issues/.

[3] Ph.D., Cardiff University.

[4] Photograph courtesy of Professor Stavroula Kousteni.

[5] The long term goal is to find out the pathogenesis of degenerative diseases for therapies. The endocrine system is a collection of glands that produces hormones. These hormones regulate numerous bodily processes including metabolism, growth and development, tissue function, sexual function, sleep, and so on. Osteoblasts are cells that form bones. Myelodysplasia (MDS) is the ineffective production of blood cells. Acute myeloid leukemia (AML) is the cancer of blood and bone marrow.

Professor Kousteni’s research has narrowed into the bone-specific hormone osteocalcin, which is transcription-regulated by osteoblast-expressed FoxO1. It became an inference to the osteoblast as an endocrine cell. That is, the bones as the endocrine system. Now, Kousteni looking into the receptor, and other functions and mechanisms, for osteocalcin.

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