Maria Gonzalez
Program: Neurosciences
Current advisor: Erik D. Herzog, PhD
Undergraduate university: University of Puerto Rico-Cayey, 2019
Enrollment year: 2020
Research summary
Glioblastoma (GBM) is a deadly disease, with an average survival post-treatment of 15 months, and no advancements in therapy since the introduction of the chemotherapeutic drug Temozolomide (TMZ) and tumor-treating fields to the standard of care. The proposed research will investigate the mechanisms by which clock gene expression in GBM tumors synchronizes to the host, whether circadian signals regulate tumor progression, and the implications this could have for timed-sensitivity to current therapies. We will characterize the times of day in which tumors are more sensitive to mitogens known to drive GBM growth and to current therapeutic drugs. This work can eventually connect the bench to the bedside to inform personalized therapy (e.g., timed TMZ and DEX) to improve individual outcomes for GBM patients and potentially other cancers.
Aim 1: Assess if daily glucocorticoid signaling entrains daily rhythms in GBM and promotes tumor growth
Aim 2: Determine the mechanisms that drive daily rhythms in TMZ efficacy in GBM
Aim 3: Develop a high-throughput screen for circadian signals that drive GBM growth
Graduate publications
Gonzalez-Aponte MF, Damato AR, Trebucq LL, Simon T, Cárdenas-García SP, Cho K, Patti GJ, Golombek DA, Chiesa JJ, Rubin JB, Herzog ED. 2024 Circadian regulation of MGMT expression and promoter methylation underlies daily rhythms in TMZ sensitivity in glioblastoma. J Neurooncol, 166(3):419-30. PMCID:
Hastings MH, Brancaccio M, Gonzalez-Aponte MF, Herzog ED. 2023 Circadian Rhythms and Astrocytes: The Good, the Bad, and the Ugly. Annu Rev Neurosci, 46():123-43