Cindy Ngo

Abstract: Metastatic breast cancer patients have a 5-year survival rate of 27% with limited treatment options. Pleiotrophin (PTN), a heparin binding cytokine, is expressed at elevated levels in several cancers, including breast cancer. Previous studies indicate PTN functions in angiogenesis, neural development, and inflammation; however, the function of PTN in breast cancer progression and metastasis has not been elucidated. In this study, we determined the effect of anti-PTN therapy (monoclonal antibody; 3B10) on breast tumor progression and pulmonary metastasis in several preclinical mouse models of breast cancer. 3B10 reduces pulmonary metastasis in several mouse breast cancer models. Tissues from these mice were analyzed by IHC, FISH, and H&E to evaluate changes in immune cell infiltration, PTN expression, and metastasis. We found that PTN is enriched at metastatic lesions and increased expression of PTN correlates with poor outcomes in breast cancer patients. Blocking PTN using 3B10 reduced immunosuppressive macrophages and increased helper T cells at the pulmonary metastatic site. Our study suggests that PTN drives a pro-metastatic, immunosuppressive tumor microenvironment that promotes tumor cell escape from the primary tumor and survival of metastatic cancer cells at the secondary sites.

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What does research mean to you? 
I see research as a one of a kind opportunity that teaches me how to navigate ambiguity, be a sponge, and be fearless. In the lab, I am able to get my hands dirty and learn new assays, which gives me a sense of empowerment because I can use my knowledge from the classroom to be productive and generate significant data. I am a sponge- learning at the highest level and trying to absorb as much understanding as I can. As I continue to work in effort of producing novel results, research also pushes me to appreciate every outcome, even if it was unexpected. In doing so, I have learned perseverance and flexibility through experiencing more failures than successes. Finally, research allows me to give back to the scientific community, one that has done so much for me by constantly motivating me to have an inquisitive mindset, always looking to learn. I see research as a form of serving the scientific community, since people are able to use your projects, knowledge, and papers to further their own work and ultimately pay it forward to future generations of scientists.
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Tell us about your journey.
My first research experience took place in high school. I was inspired after reading papers about antibacterial clays and decided to conduct experiments testing natural alternatives of antibiotics. After years of participating in science fairs, research became one of my passions, and I wanted to continue scientific exploration at a research focused university.

In my sophomore year at UT Dallas, I started working as an undergraduate research assistant under Dr. Kelli Palmer’s microbiology laboratory, whose research interest in antibiotic-resistant bacteria aligned with mine. I studied the co-evolutionary relationship of bacteriophage and E. faecalis to contribute to phage therapy as a therapeutic alternative. I also worked on designing CRISPR-based antimicrobials to obstruct pathogenic bacteria. 

With Kelli’s support, I applied to the Green Fellowship in my junior year. Though I loved my time in the Palmer Lab, I chose not to study microbiology at UT Southwestern for two reasons. I believed in order to get the most out of the Green Fellowship, I needed to branch out of my comfort zone and diversify my exposure to unfamiliar fields and techniques. On a broad level, I was interested in topics throughout immunology since they contain the potential to solve fundamental questions regarding the mechanisms of disease that could eventually advance life-saving treatments. More specifically, I was interested in pursuing cancer biology after losing a close mentor to acute myeloid leukemia. From a young age, my mentor instilled a passion for learning in me that is unwavering today. A part of me wanted to research cancer biology to give back to him, and another part of me wanted to fight cancer on the molecular level to serve those currently battling. From there, I matched into Dr. Rolf Brekken’s laboratory in the Department of Surgery and the rest is history.

What was your favorite part about the program?
Not having to worry about classes and exams is great, but my favorite part of the program was the new friendships and relationships I made. After being in quarantine for 8 months, it was so nice to meet new people. Through the Green Fellowship, I have made life long friendships with other Fellows, my graduate student Debolina, and my lab group. I have also gained a mentor for life through my Principal Investigator, Rolf.

What was the biggest thing you learned from the program?
The biggest lesson I gained from the program is how to be comfortable with the uncomfortable. I personally believe a lot of self and professional growth stems from being comfortable with the uncomfortable because when you are comfortable where you are, you get complacent, you stop challenging yourself. When working in the lab, I am constantly pushed out of my comfort zone since I am poking into the unknown to solve open-ended problems. I am experiencing a ton of failures, and it’s uncomfortable! It’s not fun! But getting used to that feeling motivated me to think creatively and try new things, which ultimately helped me grow as a scientist, student, and person. 

 

 

Advice for Future Green Fellows

1. Do what you are excited about! It should drive and energize you because science is difficult and you will face obstacles.
2. Be comfortable with the uncomfortable. This one changed my life. Embracing failures and hardships will open up many more doors that weren’t there before.
3. Ask questions. You will learn at a higher level and at a faster pace if you find the courage to speak up. So do not be afraid or think that it’s silly; everyone is understanding and knows that you’re new!
​4. Reach out to Green Fellow Alumni to gain more insight on the program and potential labs. I did that when I was applying and I couldn’t be happier that I joined the Brekken Lab.