The overall goal of the Ivy Neurological Science Internship Program is to inspire high school and undergraduate students to pursue a career in bioscience, particularly in the areas of glioma research, neuroscience or neurogenomics, by providing an opportunity to conduct hands-on biomedical research under the direct mentorship of a TGen investigator.

Program Summary

Modeled after the Helios Scholars Program, the Ivy Neurological Sciences Internship Program replicates three key features that we have found instrumental to that training program’s success:

  1. Fully-funded research internships for promising high school and undergraduate students
  2. Exposure to translational/clinical medicine leveraging existing community based partnerships
  3. Presentation of research results at the end of the program to faculty, peers, parents and community members

Ivy Neurological Science Internship Program

2020-2021

SHAUN KARAKKATTU

Junior at BASIS Mesa
Mentored by Angela Baker, Ph.D.
Brain Tumor Unit, Cancer and Cell Biology Division

Research Summary

Inhibiting the Proliferation of Patient-Derived Glioblastoma Multiforme (GBM) cells by activating Estrogen Receptor beta using estradiol and IGF-1

Glioblastoma multiforme (GBM) is the most aggressive and common type of primary brain tumor. Patients with GBM have a median survival rate between 12-14 months. There are sex-based differences that exist in the occurrence of GBM with men having a 60% higher chance of developing a tumor indicating that differences in the function of Estrogen Receptor Beta (ERβ), a known tumor suppressor, may influence tumor progression in GBM. Considering ERβ function, it was hypothesized that 17β-estradiol and IGF-1, estrogen receptor agonists, may promote ERβ function and inhibit the proliferation of GBM cells in vitro. 17β-estradiol and IGF-1 were applied to a patient-derived GBM cell line and MDA-MB-453, breast cancer cell line, in-vitro. The concentrations tested ranged from 2 to 20 nM of 17β-estradiol and IGF-1. After 48 hours of exposure, GBM cell proliferation was analyzed through a trypan blue exclusion assay. The results revealed that cell proliferation was inhibited by the estrogen receptor agonists in the patient-derived GBM cells and promoted in the MDA-MB-453 cell line which served as a positive control. In conclusion, this study presents evidence that ERβ function may indeed inhibit GBM proliferation. This study presents a potential approach to the treatment of GBM. As this study continues, more steroid hormone receptors will be tested like the Androgen Receptor which may also cause the inhibition of cell proliferation in GBM.

RAYMOND NUCUTA

Senior at BASIS Mesa
Mentored by Sen Peng, Ph.D.
Brain Tumor Unit, Cancer and Cell Biology Division

Research Summary

Sexual Differences in Glioblastoma multiforme

Women get Glioblastoma (GBM) at lower rates than men, and have higher survivability rates. In fact, for every 7 men that get GBM, only 5 women will have it. Also, a NIH study shows men and women have different genes associated with higher survival rates. With these facts in mind, I answered the question: For epigenetics/methylation, do we see sex differences in GBM, especially in estrogen receptors? I performed statistical analyses like density plots on the methylation beta values of 100s of GBM patients using public data from The  Cancer Genome Atlas Program. By the end of the summer, I found a statistically significant difference in AR expression between sexes. When looking at subtypes, I found significant difference in female Mesenchymal and male/female Classical subtypes. In addition, when investigating different regions of the genes, however, I found something quite interesting: on average, men have lower β-values than women for AR, but in the promoter region, they have higher β-values, meaning AR in men is expressed less. These results left me with a couple next steps that I am eager to investigate this summer, like: looking at more than just methylation data (RNA expression), analyzing the survivability of outliers, and figuring out if the patient’s methylation values are a result of their cancer.

JAYASHREE IYER

Arizona State University
Mentored by Nanyun Tang, Ph.D.
Brain Tumor Unit, Cancer and Cell Biology Division

Research Summary

Building an in vitro blood brain barrier model to test the influence of tight junction genes on focused ultrasound disruption to treat brain tumors

Treating primary or metastatic tumors in the brain proves challenging by virtue of the protective function of the blood brain barrier (BBB). Recently, it has been shown that low intensity focused ultrasonic (LIFU) waves stably cavitate infused microbubbles which then mechanically disrupt the tight junctions of the BBB. This leads to temporary, recoverable opening of the BBB, and passage of otherwise disqualified cancer-therapeutic drugs at precise locations targeted by the focused ultrasound. To date, potential genetic influences on the durability and vulnerability of tight junctions to LIFU have not been elucidated, nor have the determinants of tight junction repair post LIFU been thoroughly investigated. We report the development of an ultrasound transparent organ-on-chip model to test LIFU with microbubble infusion treatment on a cell-engineered BBB. The BBB is developed using brain-specific endothelial cells derived from genomically characterized induced pluripotent stem cells (iPSC). Developing preclinical models of the BBB to accommodate cell sources with tight junction genes of different allele makeup will shed light on how individuals will respond to different ultrasound frequencies.

MATTHEW LEE