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Science

Dr. Stavroula Kousteni: Nobody Should Be Dying from Cancer

Dr. Stavroula Kousteni was lucky enough to know from a very young age, at 8th grade, what she wanted to do in life, and with passion – research in the biological sciences. She spoke to The National Herald about her life and profession.

The National Herard: Tell us about your work and your passion for the field of cancer research.

Stavroula Kousteni: Medical research inspired me to understand the mechanisms of disease pathogenesis, the many unexpected ways molecules, cells, and organs interact to regulate our body functions, and how those can go awry, resulting in disease. What I find the most intriguing to understand and combat is cancer – more specifically hematological cancers: myelodysplasia (MDS) and acute myeloid leukemia (AML).

I have a lab that works on MDS and AML and various ways bone regulates metabolism and inflammation. I am the director of a new Center that was established at Columbia University, jointly supported by the Edward P. Evans Foundation for MDS and by the Herbert Irving Comprehensive

Cancer Center under the creative direction of Dr. Anil Rustgi. I am also the director of a training program funded by the NIDDK that trains graduate students in the molecular and genetic aspects of endocrine diseases.

Dr. Stavroula Kousteni at a symposium on the role of the bone marrow microenvironment in normal and malignant hematopoiesis at the annual meeting of the American Society for Bone and Mineral Research (ASBMR) September 12, 2022. Photo: Courtesy of Dr. Stavroula Kousteni

My goal as the MDS Center director is to beat the disease! To bring together the unparallel and unique talent of faculty at Columbia, basic and clinical scientists and clinicians to find novel ways to prevent it, detect it, and cure it. I want to reap the power of human and mouse genetics, the depth of large, bulk, and single-cell sequencing platforms, to harness new algorithms of systems biology approaches, and all the latest state-of-the-art molecular, cellular, and structural tools we have to look at cancer as a whole and to find ways to treat it, preventing relapse. This is the time we can do it. Fifty decades down the line and we still treat hematological cancers the exact same way we did with chemotherapy, which cures very little, or hypomethylating agents, which cure nobody. Relapse from resistant clones remains. This is what we will target. And we are now putting out a huge call to scientists and those who support science with their generosity to come together to achieve it. The latter is an integral and as important part of achieving our goal.

Through the generous contributions of philanthropists, we can fund innovative, groundbreaking research in MDS and AML. Or to recruit, train, and inspire the retainment of fellows in the field. Or to expand our resources and organize events that facilitate the exchange of ideas for novel therapeutic approaches.

Dr. Stavroula Kousteni opening the inaugural annual symposium jointly held by the Edward P. Evans Center for MDS at Columbia University and Memorial Sloan Kettering July 7, 2022. Photo: Courtesy of Dr. Stavroula Kousteni

 

TNH: How would you describe your career up till now?

SK: My research, which is my main focus, the training of graduate students and postdoctoral fellows, the mentoring of junior investigators. Contributing to task forces, shaping of scientific societies that I belong to, and contributing anything needed to our Cancer Center and my Department of Physiology and Cellular biophysics as well as the Columbia community. My career is an open field of possibilities.

TNH: What can we do when there is a genetic component to a disease?

SK: It could be a lot, and it could be nothing. It depends. There are stories of success from genetic mutations found in rare diseases. And stunning genetic discoveries have changed the prognosis and treatment of cancers. One such example is the discovery of mutations in the BRCA genes in breast cancer and the prediction that they can be inherited and increase the risk for ovarian cancer, which allows doctors to act to prevent cancer spread in patients and their families. Genetic components can enable us to predict and prevent.

Dr. Stavroula Kousteni with Dr. Azra Raza, colleague and collaborator, and clinical co-director of the Edward P. Evans Center for MDS at Columbia University and the head of the MDS clinic at Columbia. Photograph taken at the Vagelos Education Center and Columbia University Irving Medical Center during the Inaugural annual symposium jointly held by the Edward P. Evans Center for MDS at Columbia University and Memorial Sloan Kettering July 7, 2022. Photo: Courtesy of Dr. Stavroula Kousteni

TNH: Does every disease have both a genetic and an environmental component?

SK: In a sense, yes, one or the other or frequently both. Genetics can be a powerful predisposition factor to disease development, but the disease does not always develop in people with similar genetics. A condition known as age-related clonal hematopoiesis (or ARCH for short) is such an example. ARCH is the presence of very small numbers of blood cells carrying mutations in genes often seen in patients with MDS and AML. However, the people who carry them at this low frequency are healthy. Out of all of us, only 1% may develop MDS or AML. Why? We do not yet know the specifics. But we do know that environmental influences can be a determining factor. For example, cells in the bone marrow microenvironment where MDS and AML cells are born and live and multiply can influence these mutant cells in healthy patients that may eventually expand them and transform them into cancer.

My lab has a good angle on examining these pre-cancerous mechanisms emanating from the bone marrow microenvironment and how they transform healthy hematopoietic cells into malignant ones.

Dr. Stavroula Kousteni with her children, Tino (Konstantino) Spiliotopoulos and Penny (Panayiota) Spiliotopoulos, both in college, “their strength and bravery, humanity and compassion, and the dignity with which they go about their lives… energize me every day.” Photo: Courtesy of Dr. Stavroula Kousteni

TNH: In the final analysis, how do you rank the importance of genes?

SK: Our genetics can be morphed by epigenetics, which means that the environment we are exposed to can cause alterations in our genes that alter their expression levels. The environment can also change how the proteins our genes send signals and how they function; or which other proteins they interact with. Therefore, our biology and our psychology say a lot about what our genes dictate.

TNH: Death has always been part of the fabric of life. For some, though, does its avoidance go to the extreme?

SK: I have an elderly neighbor in NYC, where I live. She was a nurse, to describe better what she did, a nurse without borders. She traveled worldwide, to offer help and alleviate human disease and pain. We often chat on the street. One day she told me: “people do not know how to die anymore. Our societal structures do not help them, and their doctors do not help when the time comes.” We often drag and keep threading the thread of life beyond where it should go, when treatment may defy humanity.

Me, from my side, how can I not understand that! I fight every day in the lab to understand a painfully lethal disease and tame it. I see my clinician colleagues, collaborators, and dear friends, how they treat their patients and fight for their life and the quality of their life. And then I see how 50 years down the line, in cancer research, we still often treat patients with terribly toxic drugs that extend their often tortured life for another 1, 2, or 2.5 months. What is the answer here? It is hard to give a definitive one or an ultimate one. Maybe an educated choice. Maybe a dignified ‘letting go’. Maybe a relentless ‘holding on’. What is not a maybe, what is clear is what I feel as a scientist and human being what I need to do: a relentless fight for prevention or for a cure. Nobody should be dying from cancer.

Dr. Stavroula Kousteni and Dr. Ioanna Mosialou, a very talented scientist who was a previous trainee and is currently an assistant professor in the Department of Physiology & Cellular Biophysics at Columbia University. Photo: Courtesy of Dr. Stavroula Kousteni

TNH: Looking back on your life, do you feel that you have become the person you aspired to be?

SK: A person is the make-up of many different components. So this question may be better for me to answer by compartmentalizing it. I think I have become the compassionate and empathetic person I aspired to be in my personal and professional life. Also, I have gathered the courage to be relentless in any pursuit. I have aspired to be open-minded and not be bound by predispositions, prior hypotheses, or preconceived ideas. But as a scientist and researcher, discoverer, and human being, my answer is a big no. And I hope a no it will always be. The day I will feel I have fulfilled my aspirations as such will be the day I would have given up, and my spirit will die. What a bore would then life be. So no, thankfully not, I have not and will never become the person I aspire to be every day or the person I will aspire in the future to be.

*Edward P. Evans Chair of Myelodysplastic Syndromes (MDS) Research and Professor (in Physiology and Cellular Biophysics and in the Herbert Irving Comprehensive Cancer Center) Director, Edward P. Evans Center for MDS at Columbia University.

https://www.cancer.columbia.edu/news/evans-foundation-grant-establishes-new-center-columbia-myelodysplastic-syndromes

https://www.cancer.columbia.edu/research/researchers/edward-p-evans-center-myelodysplastic-syndromes-mds

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