Were you a science curious child? Could you elaborate on events that sparked your interest in science?
My dad is a pediatrician and I was always interested in his medical and science books. I learned about the concept of cancer from him when I was very young and was always interested in pursuing cancer research, which I did for a few years before becoming interested in immunology and immunotherapy.
Has a specific mentor, scientist or scientific discovery influenced your goals in research?
My current mentor, Professor Alison Simmons, has been instrumental in shaping my research goals for the last couple of years. Alison is a real visionary so even though I'm quite experienced, I am still constantly learning new things from her and being amazed by her new ideas and concepts. This way the work is always stimulating. She's also been enormously supportive when I approach her with ideas of my own and I couldn’t have asked for a better mentor.
I also had two amazing mentors back home in New Zealand, Dr. Graeme Finlay and Professor Bruce Baguley at the Auckland Cancer Society Research Centre.
And very importantly, my teachers from my school years; Mrs. Travers, Mr. Leslie-Ellis, Ms. Nicoll, Mrs. Carlyon, and Mr. Badger, have had a long-lasting impact on me and I would not be where I am now without them.
How have your experiences as a Celgene Research Fellow at Oxford helped shape your current career path and future goals?
I'm personally very driven to do translational research so this collaboration with industry has been invaluable in helping me gain more insights into how drug development works. In terms of future goals, I hope partnerships with pharma companies will be possible when we develop promising therapeutic agents, which is always the ultimate goal – to get the research into a stage where it can benefit patients in a clinical setting.
Your current research focuses on mechanisms of intestinal immune homeostasis in Inflammatory Bowel Disease (IBD). Which are the significant areas of unmet diagnostic or therapeutic need in IBD? Are there any promising biomarkers or therapeutic approaches on the horizon that might provide a clinical impact?
Absolutely – this is the whole point of what we do and what drives us as researchers. IBD is an enormously complex disease. When there is immune dysregulation in the gut it involves hundreds if not thousands of pathways and multiple cell types – that very delicate balance has to be perfect in order to maintain tissue homeostasis. The cause of IBD can vary greatly from patient to patient, so the challenge is to develop different therapies that complement existing ones if/when they fail, as many conventional treatments do. Right now, we're working on some therapeutic pathways that we hope will have a clinical impact.
Your research takes advantage of cutting-edge single cell technologies. With single cell genomics and proteomics, how does one make sense of the vast datasets generated, and distinguish biological noise from true signal at the cellular level?
Analysis of single cell genomics requires significant support from the best bioinformatics experts, which I’ve been lucky enough to have. As for single cell proteomics, it does take me a long time to analyze all my data properly, to make sure I answer the most biologically interesting and disease-relevant questions. When we work with patient samples, we also need to make sure the results are reproducible across multiple donors.
Your most recent manuscript, Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease, has been recently published in Cell (October 2018). Could you give us an overview of the main findings and their significance?
Some of the key highlights include:
Identification of human and murine colonic mesenchymal subsets characterized by specific transcription factor expression, functional biological pathways and anatomic localization.
- Colonic mesenchymal crypt niche cells near epithelial cells expressing SOX6, F3 and Wnt pathway genes
- Demonstration of a colitis-associated activated mesenchymal population expressing pro-inflammatory factors and Lysyl oxidase family enzymes.
- Defining the functional contribution of IBD associated activated mesenchymal cells in IBD.
- CyTOF immune monitoring of mesenchymal remodeling in IBD.
Do you have any perspectives on how validation of research tools shapes scientific reproducibility? And ultimately how it might impact drug discovery efforts in academia and industry?
Robust research tools are hugely important. I've done a lot of CyTOF and bad antibodies can waste so much of my time and energy and money. I think this is something all immunologists can agree on – trusted sources of research tools/reagents can be the difference between a high impact publication and no publication/delayed publication.
It is vital that the data we publish is of the highest quality and is correct, and that is directly influenced by the research tools available. When we profile patient samples to highlight disease-associated changes we are relying on research tools to provide accurate investigation. So, the quality of these tools is essential for all aspects of drug delivery, from target identification to validation to creating therapeutic agents and testing them.
What advice would you give to students and postdocs that like you are interested in translational research?
I'd say that finding a research environment that you're happy in is very important. Also, the topic you work on needs to be of high interest to you, otherwise it's very difficult to stick with a project you're not very passionate about and see it through despite the many ups and downs you're certainly going to encounter. If the goal is translational medicine, it would be very helpful to conduct your work in an environment that permits those kinds of developments – for example, I'm affiliated with both the MRC Weatherall Institute of Molecular Medicine and the Translational Gastroenterology Unit at the John Radcliffe Hospital in Oxford, which means I am able to access patients who give formal consent to our research team to collect their tissue samples and interrogate our research questions. So overall, I think choosing the right environment is key.
Outside the lab, what activities keep you occupied and help you balance the demands of a career in research?
To be very honest, I've not had too much time to engage in activities outside of my research or other areas of work, but whenever possible I like going cycling and going to forests.
Select Publications by Dr. Hannah Chen:
Chen HH, Parikh K, Kinchen J, Antanaviciute A, Jagielowicz M, Fawkner-Corbett D, Ashley N, Cubitt L, et al., (2018) Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease. Cell.
Chen HH, Händel N, Ngeow J, Muller J, Hühn M, Yang HT, Heindl M, Berbers RM, et al., (2017) Immune dysregulation in patients with PTEN hamartoma tumor syndrome: Analysis of FOXP3 regulatory T cells. Journal of Allergy and Clinical Immunology. PMID: 27477328.
Schwerd T, Khaled AV, Schürmann M, Chen H, Händel N, Reis A, Gillessen-Kaesbach G, Uhlig HH, Abou Jamra R. (2016) A recessive form of extreme macrocephaly and mild intellectual disability complements the spectrum of PTEN hamartoma tumour syndrome. European Journal of Human Genetics. PMID: 26443266.
Avitzur Y, Guo C, Mastropaolo LA, Bahrami E, Chen H, Zhao Z, Elkadri A, Dhillon S,et al., (2014) Mutations in tetratricopeptide repeat domain 7A result in a severe form of very early onset inflammatory bowel disease. Gastroenterology. PMID: 24417819.
Hou W, Chen H, Rojas J, Sampath P, Thorne SH. (2014) Oncolytic vaccinia virus demonstrates antiangiogenic effects mediated by targeting of VEGF. International Journal of Cancer. PMID: 24474587
Breitbach CJ, Arulanandam R, De Silva N, Thorne SH, Patt R, Daneshmand M, Moon A, Ilkow C, Burke J, Hwang TH, Heo J, Cho M, Chen H, et al., (2013) OncolyticVaccinia Virus Disrupts Tumor-Associated Vasculature in Humans. Cancer Research. PMID: 23393196.
Chen H, Sampath P, Hou W, Thorne SH. (2013) Regulating cytokine function enhances safety and activity of genetic cancer therapies. Molecular Therapy. PMID: 23281444.
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