Bastien Gerby, PhD, is the 2015 winner of the ISEH New Investigator Award, given to the best presentation by a post-doctoral fellow. Dr. Gerby is a trainee in Dr. Trang Hoang’s lab at the Institute for Research in Immunology and Cancerology (IRIC), in Montreal, Canada. He has been working in the field of hematology and stem cells for 9 years and his areas of expertise are T-acute lymphoblastic leukemia, leukemic stem cells, oncogene reprograming and genetic mouse models. He joined ISEH one year ago.
Dr. Gerby kindly participate in a Q&A session with Connections. Below he talks about his post-doc experience, his current projects, his future goals and shares with us his secret to balance work and family as a young father.
Tell us about your post-graduate education, generally. About the experience of being a post-graduate fellow.
My experience as a post-graduate fellow in Dr. Hoang’s group has given me an excellent opportunity to enrich my understanding of the fundamental mechanisms that govern the development of cancer, and to develop strong expertise in translational research for the identification of new drugs, together with project management skills and supervisory experience. Within the lab, I enjoy interacting with graduate students and post doctoral fellows working in stem cell biology, genomics, bio-statistics and mouse models. In addition, at the IRIC I benefit from a multidisciplinary scientific environment with privileged access to state-of-the-art technological facilities for the advancement of my projects. I believe that this post-doctoral experience is significantly increasing my knowledge of and my skills in cancer research.
Who has most influenced you to become a scientist, and how did they influence you?
The person who influenced me to become a scientist is my PhD supervisor, Dr. Françoise Pflumio. During my thesis, Dr. Pflumio transferred to me invaluable fundamental knowledge about hematopoiesis, leukemopoeisis, the concept of stem cell and the process of clonal evolution. In her laboratory I developed my skills in the use of xenograft models to understand the cellular and molecular heterogeneity of the leukemic stem cells from patients. Dr. Pflumio gave me the opportunity to build up several collaborations and allowed me to participate in many national and international meetings and workshops. Her belief on me and her support definitely influenced me to become a scientist.
How did you find your way to the hematology and stem cells scientific field?
I found my way to the field nine years ago, when I started my PhD with Dr. Pflumio at the Cochin Institute of Paris. The department of hematology of the Cochin Institute hosts many renowned hematologists and researchers, and therefore, gave me an optimal environment to start my projects and develop my skills in hematology. The close collaborations and discussions that I had with clinicians also confirmed my interest to work on hematological malignancies.
What is the overall aim of your research?
Current chemotherapy efficiently reduces the bulk of the tumor but fails to kill pre-leukemic stem cells (pre-LSCs) that can maintain the disease and cause relapse. Treatment is also limited by toxicity towards normal hematopoietic stem cells (HSCs). Therefore, the overall aim of my research is to find a new drug targeting specifically the pre-LSCs without affecting normal HSC functions.
Tell us a little about the subject of your presentation.
Using transgenic mouse models that reproduce the natural history of the human disease, I recently found that two human oncogenic transcription factors activate a self-renewal program that converts committed thymocyte progenitors into aberrant self-renewing pre-LSCs. Murine pre-LSCs represent a reliable and unlimited source of cellular targets to screen for small compounds that inhibit their survival and/or proliferation in a high throughput screening (HTS) format. I, therefore, designed an organotypic cell-based assay with a multiparametric read-out to conduct a small molecule screen targeting primary pre-LSCs. This distinctive strategy compared to previous screens using established cell lines, led to the identification of 2-methoxyestradiol, which inhibits pre-LSC viability and self-renewal activity and remarkably spares normal hematopoietic stem cells. Together, I proposed in my presentation that targeting pre-LSCs in a niche-like microenvironment is the right approach to find new promising leukemia treatment.
What is the most exciting or intriguing result you’ve gotten so far?
Leukemia development is a multi-step process characterized by the acquisition of diverse genetic alterations. In addition, the clonal evolution and selection processes add a level of complexity to the understanding of the disease. The most exciting results that I had so far was to demonstrate how a first oncogenic event can reprogram a normal committed progenitor into a self-renewing pre-LSC through the reactivation of a stem cell gene program. This observation is critical to understand what happens at the pre-leukemic stage before malignant transformation. Furthermore, the identification of an unrestricted source of pre-LSCs opened new ways of investigation to find targeted therapy.
What's the biggest challenge you've ever faced in your research?
First, the major challenge is that pre-LSCs are very infrequent in patients and their identification can be revealed only using ultra-sensitive next generation sequencing. This issue rules out the possibility to develop chemical screen on human pre-LSCs. Second, pre-LSCs conserve their dependency for their microenvironment, where the activation of non-cell autonomous signaling pathways is critical to maintain their viability and their self-renewal activity. Therefore, my efforts focussed on solving these two issues. First, I chose to work on a mouse model expressing human oncogenes that closely reproduce the human disease. This allowed me to identify an unlimited source of pre-LSCs for drug screening since I showed that the mechanism governing self-renewal in murine pre-LSCs is conserved in the human disease. Second, I developed a robust protocol in which pre-LSCs are maintained on stromal cells, mimicking their natural microenvironment. I optimized and miniaturized this protocol for high-throughput screening of compounds targeting pre-LSCs.
How do you balance personal life and work?
Achieving work-family life balance is often a difficult process in our productivity-driven society. Especially, post-doctoral training is the critical period to build a scientific career and sometimes it require personal sacrifices. As a young father, I think that I have found a good balance between my family life and my work by making wise decisions on the most important matters at the right moments. Having a child helped me to set my priorities in my daily life. Moreover, the world of research gives me the chance to have a certain flexibility in my work schedule. I believe that working in scientific research together with a well-balanced personal life is definitely compatible.
What are you working on most intensely right now?
My work recently led to the identification of a new drug that efficiently inhibits pre-LSC activity with undetectable effect on normal HSC properties. My ongoing efforts right now is to understand, at the molecular level, this specificity towards pre-LSCs.
In your field, what do you hope we will know in five or 10 years that we don’t know now?
In the last decade, considerable effort has been devoted to understand the complexity of leukemogenesis. New powerful whole genome sequencing revealed an important patient-to-patient heterogeneity at the molecular level. I hope that in the next ten years, we will be able to establish an accurate and low-cost diagnosis for each patient and provide individual therapies. In addition, there are right now several cellular and molecular evidences that leukemia can be initiated by the reprogramming of an aberrant stem cell gene network in a committed progenitor leading to the emergence of self-renewing pre-LSCs. I hope that future therapies will target aberrant properties of pre-LSCs in order to prevent disease relapse and turn acute leukemias into diseases with good prognosis for the benefit of patients.
Who is your most influential senior investigator mentor and how did he or she help you?
My most influential senior investigator is my current mentor, Dr. Trang Hoang. I continued my scientific progression in Dr. Hoang’s laboratory in order to acquire new skills that were very complementary with my previous training. Dr. Hoang is a founding member of IRIC. My experience with her allows me to enrich my knowledge, in particular the concepts and practice of transcription regulation in hematopoietic cells and the power of genetic approaches through the use of transgenic mouse models reproducing human disease when combined with bio-imaging and drug screening. Dr. Hoang’s experience, her open-minded attitude and enthusiasm really stimulate me. Our everyday discussions help me to achieve my research aspirations and boost my level of motivation in performing research at its highest standards and prepare me for a career as an independent researcher.
What are your future career plans?
My plan is to obtain a set of unique multidisciplinary skills and a network of mentors and collaborators that will help me to develop my own research programs and progressively to become an independent investigator and group leader.
How were you introduced to ISEH?
During my PhD.
What do you find most valuable about ISEH?
The great variety of topics covered, the presence of world leading speakers, training sessions for young investigators, as well as the participation of graduate students and post-doctoral fellows with different scientific backgrounds.
Why do you attend the ISEH Annual Scientific Meeting?
I greatly benefit from attending the ISEH because my projects align perfectly with the research topics presented at the meeting. Moreover, interaction with other participants allowed me to create valuable network and develop collaborations. Finally, the presentation of my work gives me a visibility in the field and opens opportunities for my future career.
What is your favorite ISEH Annual Scientific Meeting memory?
Without doubt, this one!
Are you planning to continue as an ISEH member?
Would you like to be more involved with the society, for as a member of the New Investigator Committee?
In the future, I would be glad to be more involved with the society.
What are your hobbies?
If you could meet one person (dead or alive) who would it be and why?
Axel Kahn is an eminent French geneticist well known for his popularization of science and his position statement about ethical questions in science such as the use of gene therapy, stem cell and cloning. He is the author of several published books that influenced my thoughts and I definitely would be glad to meet him.