Thomas Graeber

About

Thomas Graeber is faculty in the Department of Molecular and Medical Pharmacology at UCLA and a member of the Crump Institute for Molecular Imaging. His background includes physics, cancer biology, signal transduction, metabolism, computational biology, proteomics, and metabolomics. His work builds experimental and computational approaches to studying cancer signaling and metabolism from a systems perspective. His research focuses on understanding cancer signaling and metabolism through the development of genome-, proteome-, and metabolome-wide assays, and applying these to measure and model aberrant functions in cancer cells. He collaborates with clinical scientists, working directly with patient samples to translate discoveries into clinical applications. His research involves collecting high-dimensional data using mass spectrometry-based phosphoproteomic and metabolomic profiling, and developing computational approaches to overlay this data with known signaling and metabolic network structures. A key emphasis is on how cellular signaling and metabolism are rewired when cancers develop resistance to targeted therapies, such as mutant BRAF kinase inhibitors used in melanoma. His work has highlighted the importance of feedback loops in maintaining cancer signaling and metabolic homeostasis, and he explores therapeutic strategies to disrupt these loops to induce cancer cell death. His goal is to identify minimal sets of components that reflect cellular states and serve as…

Research topics

• Biology
• Cell biology
• Biochemistry
• Medicine
• Cancer research
• Pathology
• Internal medicine
• Genetics
• Immunology

Selected publications

• Metabolic reprogramming and epigenetic changes of vital organs in SARS-CoV-2–induced systemic toxicity

  JCI Insight · 2020 · 87 citations

  Extrapulmonary manifestations of COVID-19 are associated with a much higher mortality rate than pulmonary manifestations. However, little is known about the pathogenesis of systemic complications of COVID-19. Here, we create a murine model of SARS-CoV-2-induced severe systemic toxicity and multiorgan involvement by expressing the human ACE2 transgene in multiple tissues via viral delivery, followed by systemic administration of SARS-CoV-2. The animals develop a profound phenotype within 7 days w…

  DOI

• Tumor heterogeneity in VHL drives metastasis in clear cell renal cell carcinoma

  Signal Transduction and Targeted Therapy · 2023 · 74 citations

  ) cells, promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular escape. Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models. This work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.

  PublisherOA PDFDOI

• Cardiomyocytes disrupt pyrimidine biosynthesis in nonmyocytes to regulate heart repair

  Journal of Clinical Investigation · 2021 · 40 citations

  Various populations of cells are recruited to the heart after cardiac injury, but little is known about whether cardiomyocytes directly regulate heart repair. Using a murine model of ischemic cardiac injury, we demonstrate that cardiomyocytes play a pivotal role in heart repair by regulating nucleotide metabolism and fates of nonmyocytes. Cardiac injury induced the expression of the ectonucleotidase ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), which hydrolyzes extracellular ATP to…

  DOI

• Defining the ATPome reveals cross-optimization of metabolic pathways

  Nature Communications · 2020 · 37 citations

  Disrupted energy metabolism drives cell dysfunction and disease, but approaches to increase or preserve ATP are lacking. To generate a comprehensive metabolic map of genes and pathways that regulate cellular ATP-the ATPome-we conducted a genome-wide CRISPR interference/activation screen integrated with an ATP biosensor. We show that ATP level is modulated by distinct mechanisms that promote energy production or inhibit consumption. In our system HK2 is the greatest ATP consumer, indicating energ…

  PublisherOA PDFDOI

• PGC-1α drives small cell neuroendocrine cancer progression toward an ASCL1-expressing subtype with increased mitochondrial capacity

  Proceedings of the National Academy of Sciences · 2024-11-26 · 13 citations

  articleOpen access

  Adenocarcinomas from multiple tissues can converge to treatment-resistant small cell neuroendocrine (SCN) cancers composed of ASCL1, POU2F3, NEUROD1, and YAP1 subtypes. We investigated how mitochondrial metabolism influences SCN cancer (SCNC) progression. Extensive bioinformatics analyses encompassing thousands of patient tumors and human cancer cell lines uncovered enhanced expression of proliferator-activatedreceptor gamma coactivator 1-alpha (PGC-1α), a potent regulator of mitochondrial oxida…

  PublisherOA PDFDOI

Recent grants

• Mammalian models for integrated metabolic and molecular profiling of malignant glioma

  NIH · $2.7M · 2018–2023

• NIH Grant P01CA168585

  NIH · $16.9M · 2019

• Targeting Genomic Instability in Lethal Neuroendocrine Prostate Cancer

  NIH · $2.6M · 2018–2023

Frequent coauthors

• Antoni Ribas

  Parker Institute for Cancer Immunotherapy

  169 shared

• Owen N. Witte

  113 shared

• Evangelia Komisopoulou

  University of California, Los Angeles

  105 shared

• Lídia Robert

  88 shared

• Richard C. Koya

  79 shared

• Jiaoti Huang

  Duke University

  79 shared

• Jennifer Tsoi

  University of California, Los Angeles

  77 shared

• Stephen Mok

  The University of Texas MD Anderson Cancer Center

  73 shared

Education

• Ph.D., Physics

  Stanford University

  1996

• B.S., Physics

  University of California Los Angeles

  1990

Awards & honors

• Melanoma Research Alliance Established Investigator
• American Cancer Society Research Scholar

Similar researchers at University of California, Los Angeles

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