When emerging science, personal curiosity and strong desire to help others collide, a research physician must heed the call. Such is the case with Jie (Angela) Chen, MD, PhD student at Johns Hopkins Bloomberg School of Public Health. We sat down with Dr. Chen to talk about her research and her passion for the intersection of microbiology, cancer research and public health.
How did you first get interested in science and microbiome research?
I trained to work as a physician in China. I have always been interested in research, especially clinical trials and scientific studies that I believe will ultimately improve the clinical practice and health care quality. Several themes have emerged in my life that make me confident and well-suited for research: I have a persistent, strong interest in scientific scenarios, a strong curiosity regarding critical biomedical issues stemming from my clinical experience and had a wonderful research experience in the Department of Immunobiology at Yale. I was very excited to join my current PhD program, Department of Microbiology and Immunology in Johns Hopkins Bloomberg School of Public Health, which aims to engage students in the interdisciplinary aspects including microbiology, immunology and public health principles. When I did my third lab rotation in Dr. Cynthia Sears lab, I became very passionate about the work on colon tumorigenesis driven by microbiota including specific pathogenic species like enterotoxigenic Bacteroides fragilis, pks+ E. coli and Clostridium difficile, and microbial dysbiosis like bacterial biofilms.
Can you give a summary of your project?
Strong evidence reveals that host genetics and environmental factors affect the gut microbiota which acts as a likely key contributor to the development of CRC. However, the mechanisms through which the microbiota encourages and/or synergizes with genetic mutations to promote CRC remains to be fully understood. The APC gene (adenomatous polyposis coli) is the primary checkpoint for the initiation of epithelial transformation that leads to the formation of the very earliest neoplasia and has been regarded as the common gene responsible for sporadic CRC.
Our preliminary study indicated that mice with either monoallelic or biallelic inactivation of the APC gene exhibit significantly increased mucosal adherence of the gut microbiota, which may modify epithelial biology to promote cell proliferation and/or epithelial transformation. Therefore, we propose to use the mouse model of conditional biallelic APC gene inactivation in colon epithelial cells to investigate the mechanisms by which loss of APC gene function interacts the gut microbiota to promote CRC onset. A thorough characterization of microbial composition and functions over the time course of colon tumor development from microadenomas to macroadenomas in mice will advance our knowledge about microbiota-driven CRC and shed light on the development of interventions to reduce tumor formation, such as the use of prebiotics, probiotics or antibiotics.
What would a typical day be for you in the lab?
My research work uses a range of lab techniques, including bacterial infection in murine models, microbial culture and identification, DNA isolation and16S rRNA gene sequencing, RNA isolation and gene expression, cell/colonoids culture, immunoassays such as western blot, ELISA and immunohistochemistry. My typical day in the lab starts with a clear to-do-list with scheduled experiments, meeting and seminars. After collecting the results of experiments, I will analyze and interpret data, read references or talk to other researchers to figure out what further experiments need to be done.
What do you find most interesting about your project? What is the most interesting or surprising result you have found?
There has been considerable debate over the role of microbiota in colon tumorigenesis in APC+/Min mice. It remains controversial whether gut microbiota promote colon tumorigenesis or not. In our pilot studies, we found that mice with either haplo-deficiency of APC gene or biallelic inactivation of APC gene exhibit significantly increased mucosal adherence of bacteria that may precede or just respond to colon tumorigenesis. We are excited about this phenotype and wanted to explore more because mucosa-associated bacteria interact intimately with colonic epithelial cells (CECs), the cell origins of CRC. Mucosal microbial dysbiosis, as compared to luminal gut microbiota, may be a critical and direct trigger for CECs changes important to CRC.
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?
We study the microbiome using aerobic and anaerobic methods, depending on indicated situations, and 16S rRNA gene sequencing. Our preliminary findings directed our focus on the contribution of mucosa-associated microbiota in colon tumorigenesis, which may be developed to a diagnostic tool by colonoscopy biopsy. A decent characterization of microbial composition along the process of colon tumorigenesis in mice may allow us to develop interventions to reduce tumor formation, such as the use of prebiotics, probiotics or antibiotics.
What are your hobbies?
I love traveling. When I do, I get to know different cultures and make new friends. Hiking is always one of my favorite pastime activities. Being outdoors is a great way to get rid of stress and helps me stay positive when facing challenges at work or in life. I am not a super sport fan, but I have played ping-pong for more than 10 years, ever since I got ping-pong training in college. We have a ping-pong table at home and I really enjoy playing ping-pong with my friends and family for a game afternoon or night. I also love doing yoga or reading books, even if it is only a few minutes before bed. These activities improve my sleep quality and helps me work and think more efficiently in the next day.
What are the major challenges you face in your research with regards to sample collection, nucleic acid isolation and data analysis?
For the time course study across the tumorigenic process proposed in my grant, there will be a few hundred samples of mouse feces and colon specimens from which we need to isolate nucleic acid at various time points. The major challenges are to keep process consistency and quality. For data analysis, we need an advanced analytic system to reflect phylogenetic characters at species levels with higher accuracy and reproducibility. Further challenges would include how to identify critical species or consortium that promote tumorigenesis.
Which MO BIO or QIAGEN products do you use/have you used in the past and what did you like about the products?
I often use QIAamp DNA Stool Mini Kit, QIAamp Fast DNA Tissue Kit, and QIAGEN Genomic-tip 20/G for my experiments to isolate stool DNA or genomic DNA from bacterial cell culture. I am very happy using those kits as the DNA yield and purity have never disappointed me.