About

Brandon Faubert, PhD, is an Assistant Professor of Medicine at the University of Chicago, affiliated with the Department of Medicine, the Committee on Cancer Biology, and the Committee on Molecular Metabolism and Nutrition. His research laboratory focuses on understanding how metabolic reprogramming—alterations in metabolic flux within malignant cells—supports cancer cell survival, growth, and progression. Dr. Faubert's team has extensive expertise in both in vitro and in vivo metabolic analysis, including the direct measurement of tumor metabolism intra-operatively in patients. To achieve a comprehensive understanding of metabolic pathways in cancer, his lab employs a wide array of mass spectrometry platforms alongside advanced methodologies such as isotope tracing (^13C, ^2H, etc.), metabolomics, and metabolic flux analysis. These tools enable the dissection of the metabolic programs driving malignant phenotypes at both cellular and systemic levels. Complementing these biochemical techniques, the lab also uses molecular imaging technologies to noninvasively monitor tumor metabolic states in vivo, facilitating the investigation of metabolic heterogeneity across different tumor types and stages. Recent work from Dr. Faubert’s laboratory explores the metabolic alterations that occur during the metastatic cascade, aiming to uncover novel vulnerabilities that can be therapeutically targeted.

Research topics

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

Selected publications

• l-2-Hydroxyglutarate impairs neuronal differentiation through epigenetic activation of MYC expression

  Journal of Clinical Investigation · 2026-03-17

  articleOpen access

  High levels of l- and d-2-hydroxyglutarate (2HG), the reduced forms of α-ketoglutarate (αKG), are implicated in neurodevelopmental disorders and cancer by modulating αKG-dependent dioxygenases involved in histone, DNA, and RNA demethylation. L-2HG dehydrogenase (L2HGDH) deficiency, a rare autosomal recessive inborn error of metabolism associated with systemic L-2HG elevation, causes progressive neurological disability and increased brain tumor risk of unclear mechanism. Using an isogenic, patient-derived induced pluripotent stem cell system, we examined the impact of L2HGDH deficiency on neural progenitor cell (NPC) function and neuronal differentiation. L2HGDH deficiency caused L-2HG accumulation, NPC hyperproliferation, increased clonogenicity, and defective neuronal differentiation in 2D cultures and cortical spheroids. Editing the L2HGDH locus to WT reversed these effects. Inhibiting glutaminase reduced L-2HG levels and induced neuronal differentiation. L-2HG-dependent inhibition of KDM5 histone demethylases led to widespread retention of H3K4me2/3, markers of active gene expression, with prominent enrichment at the MYC locus and elevated MYC expression across multiple neural cell types. Despite broadly altered histone methylation, genetically or pharmacologically normalizing MYC completely restored neuronal differentiation. These data indicated that a primary metabolic disturbance activated MYC to favor self-renewal and suppress neuronal lineage commitment.

  PublisherOA PDFDOI

• Abstract PS2-13-04: Glucocorticoids promote metabolic reprogramming that underlies enhanced proliferation of breast cancer stem and progenitor cells under conditions of chronic stress

  Clinical Cancer Research · 2026-02-17

  article

  Abstract Glucocorticoids promote metabolic reprogramming associated with enhanced proliferation of rat mammary gland cancer cells Exposure to chronic stressors can have a significant role in both disrupting normal mammary gland development as well as potentially negatively impacting the breast cancer outcome. Glucocorticoids (GCs) are stress responsive steroid hormones that mediate cellular and physiological stress responses via activating the GC receptor (GR). While several studies have sought to understand how prolonged physiological GC exposure and GR stimulation negatively impact mammary gland health and breast cancer outcomes, much work remains to be done. We used the rat mammary gland (MG) adenocarcinoma LA7 cell line, a rat MG cancer cell line derived in vitro from an in vivo DMBA carcinogen-induced mammary tumor; to begin to uncover how chronic stress hormones might affect metabolism and energy production in MG epithelial cancer as well as elucidate the molecular mechanisms underlying these effects. LA7 cells were treated either with or without 140nM (high physiological level) of the rat GC corticosterone for 0-72 hours to mimic acute to chronic stress exposure. RNA-Seq results from the LA7 cells demonstrated that under conditions of corticosterone-induced GR stimulation there was a significant increase in expression of mitochondrial-encoded genes such as MT-ND1, MT-CO1, and MT-ATP6, suggesting an unexpected rise in mitochondrial biogenesis. In addition, several nuclear genes encoding proteins involved in mitochondrial metabolism including Isocitrate Dehydrogenase and Succinate Dehydrogenase were also upregulated. We then asked whether these metabolic gene expression changes accompanied expected cell phenotypic changes. MitoTracker Green and Red staining was used to measure mitochondrial number/mass and mitochondrial membrane potential (MMP), respectively. These experiments confirmed that both mitochondrial number/mass and MMP was significantly upregulated by chronic GR activation with GC exposure. In agreement with the MMP staining data, intracellular ATP abundance was shown to be significantly upregulated by chronic GR activation. Using a Seahorse XF Mito-Stress test we observed metabolic reprogramming showing that chronic GR activation promoted significant elevation in basal, ATP-linked, and spare capacity respiration/oxidative phosphorylation (OXPHOS). Because OXPHOS activity is integrally linked to the process of glucose metabolism, we sought to determine if chronic GR activation in the LA7 cells impacts glycolysis. To do this we performed a Seahorse XF Glycolysis Stress test, as well as measured glucose uptake and lactate secretion. The Seahorse XF Glycolysis Stress test revealed an increase in basal glycolysis and glycolytic capacity in the LA7 cells. In parallel, both glucose uptake and lactate production and secretion were also elevated. Lastly, a cellular proliferation assay showed increased cell division following chronic stress hormone exposure. Overall, these observations suggest that in addition to upregulating mitochondrial biogenesis, OXPHOS, and glycolytic activity, corticosterone can contribute to rat MG cancer cellular proliferation. These data also suggest that chronic stress exposure and the resulting GC exposure leads to increased overall cellular metabolism and energy production and promotes a shift to a highly energetic and more proliferative phenotype in a model of mammary cancer. Citation Format: J. Dowgielewicz, J. Caraveo, B. Faubert, M. McClintock, S. Conzen, M. Brady. Glucocorticoids promote metabolic reprogramming that underlies enhanced proliferation of breast cancer stem and progenitor cells under conditions of chronic stress [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-13-04.

  PublisherDOI

• A Stable Isotope Tracing Primer for the Mass Spectrometrist

  Annual Review of Analytical Chemistry · 2026-02-17

  articleOpen access

  Metabolic function plays a key role in our understanding of both biological and pathophysiological processes. Metabolism is a complex combination of intrinsic processes and environmental cues across a heterogeneous mix of cell types. To investigate metabolism, stable isotope tracing is a versatile approach to assess metabolism across scales, including in cultured cells, animal models, and humans. From the first tracing studies over a century ago, the development and utility of these studies have gone hand-in-hand with technological advances in detecting these labeled atoms, particularly with mass spectrometry. In this review, we describe the instrumentation used to measure isotopically labeled metabolites and approaches to analyze and interpret stable isotope tracing data, and discuss current challenges and opportunities for discovery with these methods.

  PublisherOA PDFDOI

• L-2-hydroxyglutarate impairs neuronal differentiation through epigenetic activation of <i>MYC</i> expression

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-19

  preprintOpen access

  ABSTRACT High levels of L- and D-2-hydroxyglutarate, the reduced forms of α-ketoglutarate (αKG), are implicated in human neurodevelopmental disorders and cancer. Both enantiomers exert effects on epigenetics by modulating a family of αKG-dependent dioxygenases involved in histone, DNA and RNA demethylation. L-2HG dehydrogenase (L2HGDH) converts L-2HG to αKG. Its deficiency is a rare, autosomal recessive inborn error of metabolism (IEM) characterized by systemic elevations of L-2HG, progressive neurological disability and a high risk of malignancy in the brain. The mechanisms behind these aberrations are unknown. Here we used an isogenic, patient-derived induced pluripotent stem cell (iPSC) system to study the impact of L2HGDH deficiency on neural progenitor cell (NPC) function and neuronal differentiation. We demonstrate that L2HGDH deficiency causes accumulation of L-2HG, NPC hyperproliferation, increased clonogenicity, excessive growth, and defective neuronal differentiation in 2D cultures and cortical spheroids. Editing the L2HGDH locus to wild-type reverses these effects. Blocking L-2HG accumulation in NPCs with a glutaminase inhibitor also induces neuronal differentiation. L-2HG-dependent inhibition of KDM5 histone demethylases leads to widespread retention of H3K4me2 and H3K4me3, markers of active gene expression. These marks are prominently elevated at the MYC locus in L2HGDH-deficient cells, and consequently cells express high MYC both in 2D culture and in many distinct cell types within cortical spheroids. Although thousands of loci display altered histone methylation, genetically or pharmacologically normalizing MYC is sufficient to completely reverse defective neuronal differentiation. These data indicate that the primary metabolic disturbance in an iPSC IEM model activates the MYC oncogene, favoring stem cell self-renewal and suppressing lineage commitment to neurons.

  PublisherOA PDFDOI

• Figure 6 from High Glucose Contribution to the TCA Cycle Is a Feature of Aggressive Non–Small Cell Lung Cancer in Patients

  2025-04-02

  preprintOpen access

  &lt;p&gt;Inhibition of complex I with IACS-010759 limits metastasis in NSCLC PDXs. &lt;b&gt;A&lt;/b&gt; and &lt;b&gt;B,&lt;/b&gt; Tumor-bearing mice were treated daily with DMSO or IACS-010759 (5 mg/kg) by oral gavage for 3–4 weeks and then infused with [U-&lt;sup&gt;13&lt;/sup&gt;C]glucose for 3 hours. Overall TCA cycle enrichment was calculated as the sum of isotopologues of citrate, malate, and glutamate and compared between DMSO- and IACS-010759–treated groups. &lt;b&gt;C&lt;/b&gt; and &lt;b&gt;D,&lt;/b&gt; Subcutaneous tumor volume calculated as (L × W&lt;sup&gt;2&lt;/sup&gt;)/2. Each line represents the growth pattern of an individual tumor. &lt;b&gt;E,&lt;/b&gt; Flow cytometry analysis of circulating tumor cells in the blood of mice engrafted with mx148. Cells were assessed for hCD45 and HLA. &lt;b&gt;F&lt;/b&gt; and &lt;b&gt;G,&lt;/b&gt; Lung and brain metastases from mx148 were evaluated by flow cytometry for mouse lineage markers and hCD45 and HLA. &lt;b&gt;H,&lt;/b&gt; Metastatic burden in the lung from mx73 was assessed by flow cytometry, as above. &lt;b&gt;I,&lt;/b&gt; Bioluminescence measurements of lung metastases. Representative BLI image (left) and quantitation (right) are displayed. &lt;b&gt;J,&lt;/b&gt; Metastatic burden in the brain from mx73 was measured by flow cytometry. &lt;b&gt;K,&lt;/b&gt; Schematic of the survival surgery approach to assess the impact of IACS-010759 on established metastases. &lt;b&gt;L,&lt;/b&gt; Measurement of axillary lymph nodes containing macrometastases. &lt;b&gt;M,&lt;/b&gt; Representative bioluminescence images of axillary lymph nodes. &lt;b&gt;N&lt;/b&gt; and &lt;b&gt;O,&lt;/b&gt; Metastatic burden in the lung (&lt;b&gt;N&lt;/b&gt;) and brain (&lt;b&gt;O&lt;/b&gt;) at the time of resection of the subcutaneous tumor (baseline) and after 2.5 weeks of treatment with DMSO or IACS-010759 subsequent to tumor resection. All data are expressed as average and SD. Statistical significance was assessed using Mann–Whitney or &lt;i&gt;t&lt;/i&gt; tests to compare treatment groups. The number of mice tested and the number of mice with measurable metastases are indicated in each graph. CTCs, circulating tumor cells; LN, lymph node. *, P&lt;0.05; **, P&lt;0.01. NS, not significant.&lt;/p&gt;

  PublisherDOI

• Supplementary Figure 1 from High Glucose Contribution to the TCA Cycle Is a Feature of Aggressive Non–Small Cell Lung Cancer in Patients

  2025-04-02

  preprintOpen access

  &lt;p&gt;(Related to Figure 1). TCA cycle labeling and metabolite abundance in tumors and lungs from NSCLC patents.&lt;/p&gt;

  PublisherDOI

• Data from High Glucose Contribution to the TCA Cycle Is a Feature of Aggressive Non–Small Cell Lung Cancer in Patients

  2025-04-02

  preprintOpen access

  &lt;div&gt;Abstract&lt;p&gt;In patients with non–small cell lung cancer (NSCLC), the relationship between tumor metabolism and clinical outcomes is unknown. Here, &lt;sup&gt;13&lt;/sup&gt;C-labeled nutrients were intraoperatively infused into more than 90 patients with surgically resectable pulmonary lesions, and metabolic properties of resected tumors were correlated with survival. In NSCLCs infused with &lt;sup&gt;13&lt;/sup&gt;C-glucose, high &lt;sup&gt;13&lt;/sup&gt;C enrichment in tricarboxylic acid (TCA) cycle intermediates conferred a HR of 3.8 for early death, typically with metastasis. To test whether these features reflect requirements for metastasis, we generated patient-derived xenografts that spontaneously metastasize to multiple organs. Treatment with an electron transport chain (ETC) inhibitor reduced glucose-derived TCA cycle labeling but did not suppress subcutaneous tumor growth. However, ETC blockade reduced the abundance of circulating cancer cells and suppressed xenograft metastatic burden in distant organs. Our data demonstrate that isotope labeling can identify metabolic properties associated with metastasis in patients and that blocking the ETC suppresses metastasis in mice.&lt;/p&gt;Significance:&lt;p&gt;Intraoperative &lt;sup&gt;13&lt;/sup&gt;C-glucose infusions in patients with NSCLC show that tumors with high labeling of TCA cycle intermediates progress rapidly, resulting in metastasis and early death. Blocking this pathway suppresses metastasis of human NSCLC cells in mice.&lt;/p&gt;&lt;/div&gt;

  PublisherDOI

• Figure 5 from High Glucose Contribution to the TCA Cycle Is a Feature of Aggressive Non–Small Cell Lung Cancer in Patients

  2025-04-02

  preprintOpen access

  &lt;p&gt;PDXs generated from primary NSCLCs spontaneously metastasize in NSG mice. &lt;b&gt;A,&lt;/b&gt; Flow cytometry analysis of lung tissue from a mouse engrafted with mx73. Cells were stained with mouse lineage markers (CD45, CD31, and TER119) and HLA. &lt;b&gt;B,&lt;/b&gt; Bioluminescence of mouse lungs bearing metastases from mx73. &lt;b&gt;C,&lt;/b&gt; IHC staining for Ki67-positive cells in lung metastasis from mx148. &lt;b&gt;D,&lt;/b&gt; Percentage of HLA-ABC–expressing cells detected in the lungs of mice bearing NSCLC PDXs. Each dot represents one mouse. Data are expressed as average and SD. The numerator and denominator reflect the number of mice with detectable HLA-ABC–expressing cells in the lung and the number of PDX-bearing mice analyzed, respectively. &lt;b&gt;E,&lt;/b&gt; CT scans of brain metastases in patients 73 and 148. Yellow arrowheads indicate metastatic lesions. &lt;b&gt;F,&lt;/b&gt; Flow cytometry analysis of mouse brains with metastatic cells from PDX mx73 (left) and PDX mx148 (right). &lt;b&gt;G,&lt;/b&gt; H&amp;E staining and IHC for CK7 in subcutaneous tumors and brains of mice bearing PDX mx73 (left) and PDX mx148 (right). &lt;b&gt;H,&lt;/b&gt; Representative bioluminescence images of brains of mice with subcutaneous mx73 and mx148 PDXs. &lt;b&gt;I,&lt;/b&gt; Summary of brain metastases observed in NSCLC PDXs. &lt;b&gt;J,&lt;/b&gt; Representative bioluminescence images of liver metastases. &lt;b&gt;K,&lt;/b&gt; Summary of liver metastasis in NSCLC PDXs. All data are expressed as average and SD. NT, not tested; SQ, subcutaneous.&lt;/p&gt;

  PublisherDOI

• Now you serine, now you don't

  Trends in Pharmacological Sciences · 2025-10-11

  articleOpen accessSenior author

  Cancer cells alter metabolic programs to support uncontrolled growth and proliferation. A new study from Scott and colleagues directly examined tumor metabolism in glioblastoma patients and discovered increased import of the amino acid serine. Excitingly, limiting serine uptake enhanced the effectiveness of chemoradiation in preclinical models of glioblastoma.

  PublisherDOI

• Supplementary Figure 2 from High Glucose Contribution to the TCA Cycle Is a Feature of Aggressive Non–Small Cell Lung Cancer in Patients

  2025-04-02

  preprintOpen access

  &lt;p&gt;(Related to Figure 2). Epithelial and myeloid cell contributions to gene expression and 13C labeling features.&lt;/p&gt;

  PublisherDOI

Frequent coauthors

• Ralph J. DeBerardinis

  The University of Texas Southwestern Medical Center

  166 shared

• Ling Cai

  50 shared

• Russell G. Jones

  Van Andel Institute

  44 shared

• Bookyung Ko

  42 shared

• Chendong Yang

  38 shared

• Jiyeon Kim

  Yale University

  35 shared

• Lauren G. Zacharias

  The University of Texas Southwestern Medical Center

  34 shared

• Benoı̂t Viollet

  Université Paris Cité

  32 shared

Labs

• Faubert LabPI

Education

• Ph.D., Physiology

  McGill University

  2015

• Other, Cancer Metabolism

  UT Southwestern

  2021