Browsing by Author "Gao, Peng"

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    A metabolic shift to the serine pathway induced by lipids fosters epigenetic reprogramming in nontransformed breast cells
    (American Association for the Advancement of Science, 2025) Eduardo, Mariana Bustamante; Cottone, Gannon; McCloskey, Curtis W.; Liu, Shiyu; Palma, Flavio R.; Zappia, Maria Paula; Islam, Abul B. M. M. K.; Gao, Peng; Setya, Joel; Dennis, Saya; Gao, Hongyu; Zhang, Qian; Xuei, Xiaoling; Luo, Yuan; Locasale, Jason; Bonini, Marcelo G.; Khokha, Rama; Frolov, Maxim V.; Benevolenskaya, Elizaveta V.; Chandel, Navdeep S.; Khan, Seema A.; Clare, Susan E.; Medical and Molecular Genetics, School of Medicine
    Lipid metabolism and the serine, one-carbon, glycine (SOG) and methionine pathways are independently and significantly correlated with estrogen receptor-negative breast cancer (ERneg BC). Here, we propose a link between lipid metabolism and ERneg BC through phosphoglycerate dehydrogenase (PHGDH), the rate-limiting enzyme in the de novo serine pathway. We demonstrate that the metabolism of the paradigmatic medium-chain fatty acid octanoic acid leads to a metabolic shift toward the SOG and methionine pathways. PHGDH plays a role in both the forward direction, contributing to the production of S-adenosylmethionine, and the reverse direction, generating the oncometabolite 2-hydroxyglutarate, leading to epigenomic reprogramming and phenotypic plasticity. The methionine cycle is closely linked to the transsulfuration pathway. Consequently, we observe that the shift increases the antioxidant glutathione, which mitigates reactive oxygen species (ROS), enabling survival of a subset of cells that have undergone DNA damage. These metabolic changes contribute to several hallmarks of cancer.
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    Designing the next-generation clinical care pathway for Alzheimer’s disease
    (Springer Nature, 2022) Hampel, Harald; Au, Rhoda; Mattke, Soeren; van der Flier, Wiesje M.; Aisen, Paul; Apostolova, Liana; Chen, Christopher; Cho, Min; De Santi, Susan; Gao, Peng; Iwata, Atsushi; Kurzman, Ricky; Saykin, Andrew J.; Teipel, Stefan; Vellas, Bruno; Vergallo, Andrea; Wang, Huali; Cummings, Jeffrey; Neurology, School of Medicine
    The reconceptualization of Alzheimer's disease (AD) as a clinical and biological construct has facilitated the development of biomarker-guided, pathway-based targeted therapies, many of which have reached late-stage development with the near-term potential to enter global clinical practice. These medical advances mark an unprecedented paradigm shift and requires an optimized global framework for clinical care pathways for AD. In this Perspective, we describe the blueprint for transitioning from the current, clinical symptom-focused and inherently late-stage diagnosis and management of AD to the next-generation pathway that incorporates biomarker-guided and digitally facilitated decision-making algorithms for risk stratification, early detection, timely diagnosis, and preventative or therapeutic interventions. We address critical and high-priority challenges, propose evidence-based strategic solutions, and emphasize that the perspectives of affected individuals and care partners need to be considered and integrated.