Tissue Engineering in Tumor Innervation Research

Author: Hailey Hoog | Major: Biomedical Engineering | Semester: Spring 2023

My name is Hailey Hoog and I just wrapped up my junior year as an honors biomedical engineering major within the College of Engineering. This was my second semester, but first funded semester, as an undergraduate member of the Therapeutic Testbed Engineering Lab under Dr. Young Hye Song of the Biomedical Engineering Department. I am completing a summer research program through Harvard Medical School this summer and will return to the lab to complete my last two semesters this upcoming academic year.

My research focuses on the metabolic regulation of breast tumor innervation, which occurs when neurites extend into solid tumors and is correlated with poor prognosis, high levels of metastasis, and high risk of cancer recurrence. Specifically, my project investigates the correlation between vitamin B12, nerve growth factor production and receptor presence, and neurite outgrowth in breast tumor innervation by quantifying the presence of neurotrophic receptors that are known to contribute to tumor proliferation and neurite outgrowth. This will be done by using a tissue-engineered hydrogel that mimics the breast tumor microenvironment with murine breast cancer cell and dorsal root ganglion co-culture. The goal is to better understand the interaction between metabolites and neurotrophins in cancer-nerve crosstalk, its implications for existing cancer therapies, and how it might contribute to developing cancer therapies that target tumor innervation. B12 was chosen as the metabolite since Metformin, a drug often used to treat hyperglycemia in breast cancer patients, is associated with B12 deficiency, prompting doctors prescribe B12 supplementation causing upregulation that may influence nerve proliferation in tumor innervation.

I honestly had no idea where to start when it came to finding a research mentor or joining a lab this time last summer–it was an intimidating task, but Dr. Chelsea Hodge and the Honors College were so helpful. I knew that I found biomaterials and tissue engineering interesting, and it was important to me that I found a topic that related to my interest in the health disparities facing Native American and Alaska Native communities. When I saw that one of the Song lab’s focuses was the role of tumor microenvironment in cancer progression and after reading through many of the publications from her lab, I reached out about joining and was paired with Emory Gregory, a PhD candidate in the Department of Biomedical Engineering, who has been a wonderful mentor. I feel incredibly fortunate to work with her and Dr. Song, as well as the rest of our lab, in an environment that is encouraging, supportive, and fun.

Emory’s focus is primarily on cancer-nerve crosstalk in pancreatic cancer and breast cancer, providing the direction for my research topic, but it was certainly still overwhelming trying to narrow that down to a specific study. Since studies have suggested that vitamin B12 is an important metabolite in cancer-nerve crosstalk, especially since certain cancer therapies often result in B12 supplementation, that is the metabolite I decided to focus on. I then completed outside literature review and worked with Emory to determine the best way to quantify the nerve growth factor presence and neurite outgrowth, eventually finalizing my study design. I learned so much about research design and general lab techniques through this process, as well as how to ask for help and guidance in research. Reading about how metabolites may worsen cancer progression has also completely ruined over-the-counter supplements for me…

This past semester, I have trained in hydrogel formation and cell culture to prepare for the rest of my project, along with histology and confocal microscopy techniques. Once I return in the Fall, I will continue to train on 3-dimensional cell culture and various assays before jumping into my project. I am so excited to see this project through and to determine if vitamin B12 level is positively correlated with nerve growth factor expression and has the hypothesized effect on neurite outgrowth. Even if it does not, this project will add to the greater understanding of cancer-nerve crosstalk and I feel incredibly privileged to play a role in that.