Hersh Nanda
Hersh Nanda
Helios Scholar
School: University of California, Los Angeles
Hometown: Gilbert, Arizona
Mentor: Sharvari Mankame and Mimi Mbegbu 
PI: Floris Barthel, MD, PhD 

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Longitudinal tracking and analysis of glioblastoma-derived cfDNA levels in response to temozolomide treatment

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults with a poor prognosis exacerbated by insufficient MRI-based GBM monitoring techniques. This project investigates the efficacy of cell-free (cfDNA) in tracking real-time GBM tumor burden in response to treatment. A longitudinal experiment, spanning 24 to 120 hours, was designed to evaluate changes in cfDNA levels over time in untreated and temozolomide (TMZ)-treated GBM samples. At those specific timepoints, the cfDNA was collected, extracted, and quantified for further analysis. Results showed a stark difference in growth patterns between the untreated and TMZ-treated GBM samples. Treated samples exhibited higher rates of cell death along further timepoints, thus validating TMZ efficacy. Additionally, TMZ-treated samples exhibited higher cfDNA yield along further timepoints that correlated with increasing dead cell counts. cfDNA yield was lower in untreated samples due to higher viability. TapeStation analysis of untreated and treated timepoint samples yielded expected fragmentation distribution results, reinforcing the potential of cfDNA as a GBM diagnostic tool. This experiment suggests that cfDNA is a successful biomarker for monitoring GBM treatment response. cfDNA can be utilized to accurately track GBM tumor growth, monitor real-time GBM treatment response, and identify relevant genetic mechanisms through sequencing.