Meet the Researcher - Abby Hill

Breakout Room: 3

Researcher Name: Abby Hill
Title of Research: Reversing Radiation Resistance in Pediatric Brain Tumors
Division Representing: Biology
Institution: University of Kentucky
Institution Location: Kentucky
Home State: Kentucky
District Number: 6
Advisor/Mentor: Nathan Vanderford
Funding Source: N/A
Scholarships: yes

Research Experience:
I have been working in a cancer research lab since my first semester of college. I mainly assisted with research involving drug screenings on zebra fish with P53 mutations, and was about to begin my first solo project when covid hit and I wasn't able to be in the lab. This poster will be my first solo project and I will be continuing with the drug screenings I was previously assisting with. I am also part of the Appalachian Career Training in Oncology (ACTION) program through the Markey Cancer center, which prepares youth from Appalachia for careers in oncology because cancer affects Appalachia disproportionately. I am also a Certified Nurse Aide. On the weekends I volunteer with Habitat for Humanity. 

Presentation Experience:
In my introductory biology course, I completed a research paper and poster about the biology of eating disorders. I presented this to my classmates and professors. I have also completed the PEERS training program to present information about e-cigarettes to groups of high school and middle school students.

Significance of Research:       
Diffuse Intrinsic Pontine Glioma (DIPG) is a childhood brain cancer that has no cure and lacks effective treatments. Surgical removal of the tumor is nearly impossible because it invasively grows into the brainstem. The current standard of care for DIPG is radiation treatment. However, all DIPG tumors become radiation-resistant over time, and fewer than 1% of children with DIPG survive more than five years post-diagnosis. Mutations that inactivate the gene TP53 are associated with radioresistance in DIPG. In my research, I found that a zebrafish strain that is tp53 mutant was largely resistant to the effects of gamma-irradiation, with nearly 100% of animals surviving radiation doses that kill tp53 wild-type embryos. I used this zebrafish strain to screen a 1400 compound FDA-approved library to identify drugs that could restore radiation sensitivity to the tp53 mutant larvae. Eleven potential drug candidates were identified that sensitized larvae to irradiation, with no negative effect on control animals that weren't irradiated. These drugs will be applied to human radioresistant DIPG cell lines with TP53 mutation, and the ability for the drug to revert the radioresistant phenotype will be quantified. Gene expression changes will be compared between control and drug treated cells from the top 3 drug candidates to determine possible molecular mechanisms by which the drugs restore radiation sensitivity to TP53 mutant DIPG. Identification of mechanisms of radioresistance in DIPG can lead to discovery of new drug targets, and the use of FDA-approved compounds could lead to clinical trials to revert radioresistance in DIPG.

Uniqueness of Research: 
This research will find drugs that can be repurposed to better treat a deadly type of childhood cancer. By identifying drugs that can restore radioresistance in DIPG and also identifying mechanisms of radio resistance in DIPG, new drug targets can be identified