I knew I wanted to do research at some point in my vet school career, because I think research is so far-reaching and can have a widespread positive impact on therapies we give our patients and a positive difference in the lives of people and animals alike. Realizing new interests as I'm learning and then having the opportunity to explore those further through the countless opportunities that exist at Cummings School has been amazing. There are so many doors that can be opened if you just reach out. Everyone is so willing to help and have you involved in some way.
Student Summer Researcher: Jessie King, V29
King continued the work of cardiology research intern Dr. Kate Murphy, studying a therapy for hemangiosarcoma in the Yang Lab
Key investigators on a study soon to come out of the Yang Laboratory at Cummings School of Veterinary Medicine at Tufts University were cardiology research intern Dr. Kate Murphy (she/her) and Jessie King, V29 (she/her), who wrapped up the study for her student summer research project. Led by principal investigator Dr. Vicky Yang, V09, associate professor in the Department of Small Animal Clinical Sciences at Cummings School, the study evaluated treatments for hemangiosarcoma, one of the more commonly seen tumors in dogs.
Research at the Yang Lab focuses on discovering new insights and improving therapies for veterinary cardiovascular diseases and disorders that can potentially translate to human health. Murphy’s role in the lab included investigating the effects of a drug often used in tandem with a cancer medication for hemangiosarcoma. She also jumped in on additional research projects with other faculty during her internship. Before she left for residency at the University of Florida in June, she trained King to complete the work as part of Cummings School’s Student Summer Research Program.
“We always value training those with an interest in becoming clinician-scientists: future vets who want to contribute to cutting-edge science. Participating in research helps develop independent thinking,” says Yang, advisor for both Murphy and King. “It was great that Kate was able to mentor Jessie at the beginning of summer. This showcased all that Kate had learned in the year and started teaching others. It was great to see them problem-solve and teach themselves new things.”
King’s summer research project, “Dissecting the Beta-Receptor Pathway in Hemangiosarcoma Cells Treated with Carvedilol,” was an award winner in the Basic Research category at Cummings School’s 37th Annual Veterinary Research Day last week.
Hemangiosarcoma is a malignant and aggressive form of cancer that originates in cells lining blood vessels. Hemangiosarcoma can affect most dog breeds, is difficult to treat and often fatal. One of the main treatment options is a chemotherapeutic medication called doxorubicin, which can be toxic to the heart and could potentially lead to cardiac disease. Studies in human medicine have shown that by simultaneously administering a beta-blocker (a medication that lowers heart rate and blood pressure) can be cardioprotective while treating hemangiosarcoma. Consequently, veterinarians sometimes prescribe the beta-blocker carvedilol to patients with hemangiosarcoma treated with doxorubicin to mitigate the latter’s toxic effects on the heart. This study examines carvedilol’s effects on hemangiosarcoma cells to determine whether these two medications should in fact be prescribed together.
“Our goal is to determine the best way to treat hemangiosarcoma,” says Murphy. “We want to make sure that we find a drug that helps protect the heart while we're still able to use our most effective treatment, doxorubicin, to target the cancer.”
Murphy focused her research on beta-pathways most affected by carvedilol. One of her first tests evaluated the viability of hemangiosarcoma cells when treated with carvedilol at various dosing levels. After running the assays, she found that higher concentrations of carvedilol had a small effect on reducing hemangiosarcoma cell viability, a positive result. The research team also wanted to ensure carvedilol did not affect doxorubicin's effectiveness in killing cancer cells. She found in the assays and cell cultures that when administering both drugs, doxorubicin was just as effective as when used alone.
“When we combine those drugs, we're still seeing a lot of cell death and decrease in cell viability that’s statistically significant, which we're happy about,” says Murphy. “That tells us that carvedilol in combination with doxorubicin is not having a negative effect on the efficacy of doxorubicin, which is great. The next step is where Jesse comes in.”
King’s task was to evaluate the beta-adrenergic pathways affected by both drugs to better understand how carvedilol reduces hemangiosarcoma cell viability. This was King’s first experience working in a lab.
“I knew I wanted to do research at some point in my vet school career, because I think research is so far-reaching and can have a widespread positive impact on therapies we give our patients and a positive difference in the lives of people and animals alike,” says King. “Realizing new interests as I'm learning and then having the opportunity to explore those further through the countless opportunities that exist at Cummings School has been amazing. There are so many doors that can be opened if you just reach out. Everyone is so willing to help and have you involved in some way.”
King found that one of the challenges with working with cancer cells collected from real dog patients is how each of these cells can behave slightly differently from those of another patient. Carvedilol had more noticeable effects in the pathway she examined in some cells but not others, an unexpected result.
On her experience working in the Yang Lab, King says, “There have been some learning curves. I'm really grateful to Dr. Yang, Dr. Murphy, and Dawn Meola [laboratory manager and research assistant in the Yang Lab] because they've all been so supportive in training me. This research in the future may have the potential to better the way that the therapy exists right now, and that's really exciting.”
Murphy and King are now working on the manuscript, which will guide the next project for the Yang Lab.
“Our end goal is how can we better treat cancer in some of these dog patients,” says Murphy. “We always want to think about the heart with doxorubicin and make sure that we're not causing more problems for our patients in the end. We're hoping that this can be a good segue to do more clinical trials at some point.”
On her first foray into research, King reflects, “It is an invaluable experience. In my case, it opened my eyes to working in a lab, what research is all about, and how you have to try and fail, and sometimes your hypothesis is not what your results will be. We get to work one-on-one with research mentors and really learn what the job looks like, how this could be incorporated into veterinary medicine, and our future careers.”