Kari Wilder-Romans

Microenvironment-derived acetylated amino acids promote glioblastoma treatment resistance

Daniel Wahl, Palavalasa Sravya, Leyla Altay, Kathy Do et autres

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Rac1 and CHK1 Converge on Abi-1 to Regulate DNA Repair Dependency and Treatment Response in Human Cancers

Yiheng Huang, Elizabeth C. McCulla, Jihan Park, Annabel Yang et autres

Radiation therapy (RT) resistance remains a major clinical challenge, yet biomarkers guiding precision radiosensitization are lacking. We previously demonstrated that Rac1 promotes RT resistance in glioblastoma (GBM) by inducing Abi-1-S323 dephosphorylation and enhancing non-homologous end joining (NHEJ). Here, we identify Abi-1-S323 as …

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Abstract 4645: Integrative transcriptomic and CRISPRi screening identifies determinants of intrinsic radiosensitivity in breast cancer

Breanna Nicole McBean, Priyanka S. Rana, Reine Abou Zeidane, A. Davis et autres

Abstract Background: Breast cancer (BC) remains a leading cause of cancer-related mortality among women, and radiation therapy (RT) is a cornerstone of its management. Despite its efficacy, more than 15% of patients experience locoregional recurrence following RT, highlighting a critical need to …

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Adaptive nuclear GTP synthesis promotes glioblastoma treatment resistance and is a targetable vulnerability in patients

Andrew J. Scott, Ningning Liang, Wajd N. Al‐Holou, Jie Xu et autres

Abstract Glioblastoma (GBM), the most lethal of all brain cancers, resists therapy by rewiring metabolism and relying on GTP signaling to promote DNA repair and radiation therapy (RT) resistance. How GBM modulates GTP levels for this signaling in response to RT-induced DNA …

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TMET-54. Rewiring of cortical glucose metabolism fuels human brain cancer growth

Andrew J. Scott, Anjali Mittal, Baharan Meghdadi, Alexandra O’Brien et autres

Abstract The brain avidly consumes glucose to fuel neurophysiology. Cancers of the brain, such as glioblastoma (GBM), relinquish physiological integrity and gain the ability to proliferate and invade healthy tissue. How brain cancers rewire glucose utilization to drive aggressive growth remains elusive. …

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TMIC-85. Microenvironment-derived acetylated amino acids promote glioblastoma DNA repair by rerouting glucose fates and enhancing histone acetylation

Sravya Palavalasa, Jack Freeman, Aditri Gokul, Ava Singer et autres

Abstract Genotoxic therapy resistance in glioblastoma (GBM) is mediated by rapid DNA repair. We hypothesized that non-malignant cells in the heterogenous GBM microenvironment assist rapid DNA repair in neoplastic cells. Supporting this hypothesis, intracranial GBM tumors (orthotopic GBM PDXs and syngeneic murine …

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Rewiring of cortical glucose metabolism fuels human brain cancer growth

Andrew J. Scott, Anjali Mittal, Baharan Meghdadi, Alexandra O’Brien et autres

The brain avidly consumes glucose to fuel neurophysiology1. Cancers of the brain, such as glioblastoma, relinquish physiological integrity and gain the ability to proliferate and invade healthy tissue2. How brain cancers rewire glucose use to drive aggressive growth remains unclear. Here we …

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Targeting monopolar spindle kinase I (Mps1 or TTK) induces radiosensitization in syngeneic models of triple negative breast cancer (TNBC) and potentiates type I interferon (T1IFN) signaling

Kassidy M. Jungles, Caroline Bishop, Cydnee Wilson, Meilan Liu et autres

Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that disproportionately impacts Black women and has limited effective therapeutic options. Consequently, there is an urgent need to develop novel approaches for the treatment of TNBC. Previously, we identified monopolar spindle …

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Identification and Characterization of PCAHIT, a Novel Long Non-Coding RNA Associated with Poor Outcomes in Prostate Cancer

Hui Li, Noah Younger, Bhavna Malik, Hyun Jin Shin et autres

Despite extensive investigation, the factors promoting aggressive prostate cancer are poorly understood. By performing a comprehensive analysis of whole-genome transcriptome data to identify differential expression across 1,567 patients with prostate cancer, we now report the identification of a novel lncRNA, Prostate Locus …

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Abstract 1469: Deciphering mechanisms of intrinsic radioresistance in breast cancer: Insights from transcriptomics and CRISPRi screens

Breanna McBean, Priyanka S. Rana, Benjamin J. Hauk, Anna R. Michmerhuizen et autres

Abstract Background: Breast cancer (BC), the most common cancer globally and a leading cause of death in women, often utilizes radiation therapy (RT) as part of treatment, with over 85% of patients receiving RT after breast-conserving surgery. Still, over 15% of women …

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Reciprocal links between methionine metabolism, DNA repair and therapy resistance in glioblastoma

Navyateja Korimerla, Baharan Meghdadi, Isra Haq, Kari Wilder-Romans et autres

ABSTRACT Glioblastoma (GBM) is uniformly lethal due to profound treatment resistance. Altered cellular metabolism is a key mediator of GBM treatment resistance. Uptake of the essential sulfur-containing amino acid methionine is drastically elevated in GBMs compared to normal cells, however, it is …

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TMIC-25. MICROGLIA IN THE GLIOBLASTOMA MICROENVIRONMENT SECRETE ACETYLATED AMINO ACIDS WHICH ASSIST IN THE REPAIR OF RADIATION INDUCED DNA DAMAGE

Sravya Palavalasa, Jack Freeman, Ava Singer, Aditri Gokul et autres

Abstract Rapid repair of DNA damage mediates genotoxic therapy resistance and poor prognosis in glioblastoma (GBM). The GBM tumor microenvironment (TME) is heterogenous, and we hypothesized that non-malignant cells support the repair of DNA damage in glioblastoma cells. Consistent with this hypothesis, …

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