Pathology will stay as a cornerstone of personalized medicine

MUDr. Mariam Gachechiladze, Ph.D. studovala medicínu v gruzínském Tbilisi a na tamní Tbilisi State Medical University graduovala v roce 2010. Své postgraduální studium však zahájila na Ústavu klinické a molekulární patologie Lékařské fakulty v Olomouci a Ph.D. zde získala v roce 2015. Během svého Ph.D. studia absolvovala několikaměsíční stáž ve Velké Británii na univerzitě v Birminghamu. Jejím hlavním odborným zájmem je oblast plicních karcinomů; té byla také věnována práce, za kterou letos obdržela Lamblovu cenu od výboru naší společnosti.

This year, you became a winner of the Lambl Award for the best publication of young researcher from our society in the last year. The awarded paper „Prognostic and predictive value of loss of nuclear RAD51 immunoreactivity in resected non-small cell lung cancer patients“ was published in Lung Cancer journal in March 2017. Could you please briefly summarize the awarded work/paper?

Targeting deficient DNA repair has been an attractive target for cancer treatment for several decades. However, despite extensive efforts, still there is no valid biomarker implemented in clinical practice, which can reliably reflect individual tumor DNA repair capacity and predict the patient outcome after DNA damaging treatment. RAD51 protein plays central role in DNA repair via homologous recombination, the major pathway ensuring cellular genomic stability. In our awarded study we investigated the potential prognostic and predictive value of RAD51 in a large cohort of non-small-cell lung cancer (NSCLC) patients. Originally, it was the common idea of me and Dr. Markus Joerger, MD, PhD, ClinPharm, from the Department of Oncology & Hematology, Cantonal Hospital St. Gallen, Switzerland. Initial work, which included 90 NSCLC patients, was performed at the Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Palacky University, Olomouc, Czech Republic. Due to the fact that our results were not in line with previously published literature, we were in search of another, potentially larger NSCLC cohort to validate our results. That’s how I met Prof. Dr. Med. Alex Soltermann, PhD from The Institute of Pathology, University Hospital Zurich, Switzerland, who is the leading lung pathologist. He liked the idea of the study and allowed us to investigate RAD51 protein expression in 1109 NSCLC patients from University Hospital Zurich. In the end, both study cohorts showed that the loss of RAD51 is quite frequent event in NSCLC patients and it is linked to poor prognosis in surgically treated patient group, potentially as a result of deficient DNA repair and increased genomic instability. Due to the fact that increased genomic instability is also associated with increased mutational burden and increased neoantigen load on tumor cell surface, which are the markers of immunotherapy response, we are now considering to explore the potential link between RAD51 protein expression and immunomodulatory tumor microenvironment in NSCLC patients. The study is currently ongoing again in collaboration with University Hospital Zurich.

I wonder, what was your journey to the Czech Republic, to Olomouc?

During my studies as a medical student in Tbilisi State Medical University, Republic of Georgia, I was working as an undergraduate student fellow at the Department of Pathological Anatomy under the supervision of Professor George Burkadze, MD, PhD, who is the leading pathologist in Georgia. Professor George Burkadze has a long lasting and successful collaboration with Professor Zdenek Kolar, MD, PhD, the head of the Department of Clinical and Molecular Pathology in Olomouc, and it was there common agreement to send the successful Georgian students for the PhD study to Olomouc. I would like to kindly thank both professor Burkadze and professor Kolar for their kind will to make this happen. During my PhD study I was investigating the molecular markers of drug resistant NSCLC under the supervision of Docent Josef Skarda, MD, PhD, to whom I would like to take a chance and thank a lot for his generous supervision and invaluable contribution to my professional development.

And how did you become a pathologist?

During my medical studies I was really fascinated with the beauty of microscopic world. I am also considering pathology as one of the most interesting and challenging field of medicine and I like to be challenged. At the moment I am still at the beginning of my pathologist career and I hope to become one of the successful pathologists in Europe.

What is your field of expertise in pathology?

The field of my expertise in pathology is lung cancer, which is also my major research interest. Lung cancer still remains as a leading cause of cancer related mortality worldwide, and I think that extensive research in this field is really important.

How do you perceive the latest progress of modern pathology. How do you see the future of pathology.

Pathology witnessed a dramatic progress during last century. Still in one century ago, the main task of pathologist was to perform autopsies and provide the postmortem diagnostics. There was even joke about pathologists, saying that these doctors do everything and know everything but a bit too late. Situation has been changed about fifty years ago, when the diagnostics of biopsy and surgical material from alive patients came into focus. Later the diagnostic process has been significantly improved with the development of immunohistochemistry and other molecular
biology and genetic methods. Latest progress of pathology is reflected by the development of therapeutic diagnostics. Nowadays, pathology provides not only diagnostic and prognostic information but also guides the treatment decisions. There are an increasing scientific efforts to identify more therapeutic biomarkers, especially in cancer patients, around the world, and I am proud that Olomouc is an important part of the world class scientific research in this field, thanks to it’s recently opened Institute of Molecular and Translational Medicine (IMTM).  I believe that in future the importance of pathology will be increasing and it will stay as a cornerstone of personalized medicine.

What are your personal and professional expectations for the future?

I would like to settle down in Czech Republic as I think that it is one of the most beautiful and peaceful countries in the World. I also expect from myself to become one of the successful pathologists in Czech Republic. I plan to dedicate equal amount of time and efforts to diagnostics as well as research in pathology.

And what do you do when not working?

I am frequently saying that my work is my hobby as well, as I enjoy it so much. However, in my free time I like to read classical literature and go for swimming. I also like traveling in different beautiful cities around the Europe and visiting art museums.

-jz-