As a part of our Microbiome Awards winners interview series, we spoke with Dr. Hannah Wardill of The University of Adelaide and The University Medical Centre Groningen. Dr. Wardill is the grand prize winner in the PhD Scientist Category of the 2018 Microbiome Awards. Her project aims to apply knowledge in in the field of oncogastroenterology to provide precision medicine to children with cancer. We interviewed Dr. Wardill to discuss her current research and future plans.
How did you first get interested in science and microbiome research?
I have always shown curiosity for the world around me; [I have been] driven to solve problems and [am] intrigued by ingenious solutions. As such, a career in science was always suited for me. Even as a young child, I was involved in many science programs. [I was] awarded the Oliphant Science Award in 2000, when I was only 10 years old. When deciding which field of science I wanted to pursue, medical sciences were a clear choice as I have always had an insatiable quest to solve problems relating to human disease. Originally, I was interested in pure cancer biology reflecting the prevalence of cancer in my own family and the presence of a heritable mutation in my extended family predisposing to bowel cancer (Lynch Syndrome/HNPCC). However, in an undergraduate project, I became exposed to the work being conducted in supportive cancer care at the University of Adelaide. In addition to being completely inspired by my supervisors at the time, the research field resonated with me because I felt I could have a genuine impact on peoples’ lives undergoing cancer treatment. I was driven to challenge the view that side effects of chemotherapy are “unavoidable” or a “necessary evil” that patients must endure in order to achieve remission. I am highly competitive, and I saw this as a challenge to eliminate some of the most debilitating side effects, thus making the lives of people undergoing treatment not only tolerable, but also enjoyable.
I started studying the microbiome during my PhD, after some of research showed that the main gatekeeper between the microbiome and the immune system was critical in the development of diarrhea after chemotherapy. I think I am particularly drawn to the microbiome due to it being an almost ‘untapped’ organ. I love the fact that we are more bug than human, yet this organ really hasn’t received the attention it deserves. I love the fact that I am on the forefront of microbiome research, with a growing potential for impact, both scientifically and clinically.
Can you give a summary of your project submitted for the Microbiome Awards?
Our ability to treat cancer has grown exponentially, driven by a deeper understanding of tumour dynamics and identification of new biological targets. This has certainly improved the long-term outlook for many people with cancer, particularly children, with the 5-year survival rate of pediatric cancers now >80%. Although these advances have undoubtedly improved the outlook for pediatric cancer, they have come at the cost of patient quality of life, both acutely and chronically, with children subject to debilitating treatment-related toxicities and long-term health implications.
My project aims to understand how a child’s unique microbiome regulates their response to cancer treatment. In combination with various patient-specific factors, I am developing a microbial algorithm to predict treatment response thus enabling implementation of personalised treatment strategies. I also hope to follow these children long after their treatment has finished to characterise how their microbiome is affected chronically, and to determine if these changes contribute to the chronic health implications children typically experience years after treatment.
What will be a typical day for you in the lab?
I currently work at the University Medical Centre Groningen, the Netherlands, in the pediatrics research laboratory. My work integrates all aspects of biomedical research, underpinned by paralleled bench-to-bedside and bedside-to-bench research. This aspect is key to my research, in which clinical phenomena drive my preclinical and ex vivo studies. I very much enjoy dissecting causative mechanisms of host-microbe interactions using ex vivo organoid models, as well as studying various interventions using preclinical models. This compliments my clinical research conducted at the Princess Maxima Hospital, in which I coordinate the collection of stool, blood and saliva from children to understand the interactions between their microbiome, immune system and genetics and how they contribute to their treatment outcomes.
What do you find most interesting about your project? What is the most interesting or surprising result you have found?
My project remains in its infancy, with my transition to pediatric oncology only recent. However, it follows on from a body of research I conducted in comparable adult cohorts, in which I have demonstrated that specific bacteria appear to be critical in shaping their response to chemotherapy. In a small pilot study I conducted last year, I was able to show a strong signal for pre-treatment Blautia protecting against treatment toxicity in people undergoing treatment for colorectal cancer. To see such a strong result in a fairly small pilot cohort was extremely encouraging and has been pivotal in directing my current and future research. It has also been important in validating my approach in pediatric cohorts. I am now most excited to establish a pediatric BioBank for the longitudinal analysis of the microbiome in childhood cancer, with the long-term goal of providing a fecal transplant service for both adult and childhood cancers.
What kind of microbiome research do you perform and how does it impact health and disease or the environment? Where do you see this heading in the next five years?
My work very much falls within the area of translational research, underpinned by a strong desire to provide clinically relevant results. My program of clinical research is aimed at identifying microbial predictors of treatment response in childhood cancer and understanding the long-term changes in the microbiome in survivors of childhood cancer.
Developing a predictive model of treatment outcomes in pediatric cancer will improve the outcomes for children with cancer in a number of distinct ways. Firstly, it will enable identification of children at high risk of toxicity before they start their treatment, enabling personalised treatment strategies to be adopted. This may be in the form of altered chemotherapy dosing, or simply the targeted and proactive provision of supportive care interventions. There is also great power in providing prognostic information to patients and their families, particularly regarding their anticipated quality of life throughout treatment. Secondly, identification of microbial-dependent risk factors will perfectly guide the development of prophylactic interventions designed to mitigate toxicity in highrisk children or enhance efficacy in 'poor responders'. This is the most important element of my research, as current efforts to target the microbiome using generic probiotic formulations have largely failed. This highlights the lack of evidence-based approaches to probiotic interventions, in which narrow spectrum commensal microbes are delivered without proper identification of the species required for optimal treatment response(s).
I anticipate that in 5 years time, our knowledge of the microbiome will be astounding. I hope to have established a BioBank, populated with the stool of people (children and adults) before they undergo cancer therapy. These samples will be characterized both on a microbiological level and clinically, providing unprecedented understanding of how an individual’s microbiome determines the success of their cancer therapy. I hope that by that point, we would have identified the microbial phenotype associated with optimal treatment responses, enabling manipulation of the microbiome to enhance the outcomes of cancer treatment. This may be in the form of a fecal transplant, in which the patient’s own stool is banked and re-administered to them throughout treatment to maintain their own unique microbial environment. Alternatively, we may see synthesized fecal transplants, in which the ideal microbial composition is provided to patients. Both options have their own benefits and drawbacks, and it will therefore be interesting to see where this field of research goes.
What are your hobbies?
I enjoy travelling, and all that comes with it, particularly the food cultures of new countries. I really love taking cooking classes when I am on holidays, and recently did one in Italy, learning to make fresh pasta! Since moving to the Netherlands, I have learned to love bike riding with the flat countryside making it very easy to explore the surrounding towns.
What are the major challenges you face in your research with regards to sample collection, nucleic acid isolation and data analysis?
The major challenge I face within microbiome research is extracting clinically relevant findings from the large amount of data obtained from microbiome analyses. As described, I am aiming to develop a predictive algorithm, which incorporates numerous patient-specific factors including genetics, peripheral immune competency and their microbiome composition. This is a huge amount of data to synthesize, and thus I have established a strong relationship with the stats department! In addition, sample collection always presents as a challenge, with many people surprisingly hesitant to part with their poo! This has actually become less of a problem as my research increasingly focuses on childhood cancers, with children certainly more open to giving you their poo.
However, it is not without its challenges, as the samples I collect are not only used for genomic analysis of bacterial composition, but they are also prepared in a way that makes them suitable for fecal transplantation. This means that they need to be collected aseptically, kept cool for minimal amounts of time and prepared anaerobically. Within the supportive oncology system, ensuring that the stool is collected appropriately can be challenging as there are many other, more important, things for the patient and their families to consider. Furthermore, in many cases, participants in our studies are treated as out-patients, and thus they are required to collect and send their samples to our laboratory via the mail. This can be logistically challenging and is often a pressure point for people when deciding if they would like to be involved in our studies.
Which QIAGEN products do you use/have you used in the past and what did you like about the products?
I have actually used only DNA/RNA extraction kits from QIAGEN, as we have not had the capacity to perform our own sequencing on site (relying on off-site services – this is something we hope to change in the future as we become more established). However, from my experience with these kits, they are extremely user friendly with clear instructions. I have had no problems with these kits before.
What was your reaction when you found out you were a finalist in the Microbiome Awards?
At the moment, the microbiome is certainly a hot topic… with almost everyone wanting to jump on the microbiome bandwagon! It seems the microbiome is now linked with almost every disease imaginable, and with this comes an increasingly large pool of scientists tackling similar research questions. Although it is wonderful to see the microbiome receiving the recognition it deserves, it can be quite daunting for a young researcher trying to establish themselves it such a highly competitive research area. To have my research recognized on a scale such as this is extremely validating and reinforces the importance and rigor of my work. As such, I am extremely proud and humbled to be named a finalist in the Microbiome Awards.