“For me, SPARK equals opportunity—it allowed me to work on a meaningful project of my own that will help shed light on how our gut can influence our risk for cancer. This experience also prepared me for the next steps in my career, as many institutions and companies want to hire researchers with the skill of communicating science to the general public.”
Can the Environment Give You Cancer?
FUNDED: FEBRUARY 2018
FUNDED BY: The generosity of Rachel and Robert Perlmutter and The Thomas C. Ackerman Foundation
What was the goal of your SPARK project?
In the Unites States, every three minutes somebody gets diagnosed with blood cancer and every nine minutes, somebody dies from it, making it one of the most fatal cancer types. Yet, we still do not fully understand the causes and factors that contribute to the disease. Mutations in certain genes like TET2 are often found in leukemia patients, but, there are healthy individuals harboring these mutations without developing leukemia. Thus, secondary factors might be necessary to trigger the disease. Similar to humans, we found a mouse model of TET2 mutant mice, which develop several types of cancer in some animal facilities while staying healthy in others. Therefore, the aim of our study was to determine whether environmental influences like infections or chronic inflammation are involved in cancer development in these mice. The SPARK award was used to purchase and maintain wildtype (WT) and TET2 mutant mice at the LJI facility, sequence their gut microbiome, and perform pilot infectious experiments.
SPARK project results:
The first step of our project was to sequence the gut microbiome of wildtype mice and healthy TET2 mutant mice in LJI’s facility to establish whether they would have similar microbiomes. Dr. Bana Jabri, at the University of Chicago had recently published that their wildtype mice and sick TET2 mutant mice harbored a similar microbiome, so it was important for us to confirm whether the same was true for the mice in LJI’s facility. Once this was established, we were then interested in comparing the difference in the gut bacteria between the healthy TET2 mutant mice at LJI and the sick TET2 mice at the University of Chicago. This comparison found that our healthy TET2 mutant mice have a more diverse microbiome and lack certain bacteria that are known to promote gut inflammation. To further analyze if inflammationcausing bacteria can trigger cancer development in TET2 mutant mice, we colonized these and wildtype mice either with an acute inflammationcausing bacteria species or chronic but mild inflammation-causing bacteria species and then compared them to control groups that received saline. Interestingly, only the TET2 mutant mice infected with the acute inflammation-causing bacteria showed elevated myeloid cell levels in their blood four weeks after infection. This suggests a strong inflammatory signal might be involved as a first step in triggering cell expansion during disease onset.
What’s next for this project?
The SPARK Award was crucial in obtaining preliminary data suggesting acute gut inflammation plays a role in cell expansion during leukemia development. The next steps are to validate the findings of this experiment. Future experiments will address whether repeated infection with the acute inflammation-causing bacteria and other strong proinflammatory stimuli contribute not just to cell expansion but also to secondary mutations, gut barrier function deficiency, and, finally, tumor development. It’s our hope that our studies will shed light on whether preventing infections and chronic inflammation might suppress cancer development and provide new insight into the therapeutic potential of targeting the microbiome of patients carrying a TET2 mutation.
What’s next for Nadine?
Recently, I’ve taken the next step in my career by accepting a new position as a Non-Clinical Scientist at Intercept Pharmaceuticals, a company specializing in progressive, non-viral liver disease. At Intercept, I design and manage non-clinical studies at CROs, collaborate with external research departments, and focus on exploratory sub-studies from Intercept’s clinical trials.