Samuel McBrayer, Ph.D. Titles and Appointments Assistant Professor Schools Medical School | Graduate School Departments Children's Medical Center Research Institute at UT Southwestern | Pediatrics Graduate Programs Cancer Biology, Genetics, Development and Disease Biography Sam McBrayer received his bachelor’s degree in biochemistry from Baylor University and went on to obtain his Ph.D. in cancer biology from Northwestern University’s Feinberg School of Medicine. At Northwestern, he worked to explain the molecular underpinnings of enhanced glucose transport activity in multiple myeloma in the laboratory of Dr. Steven Rosen. Dr. McBrayer then joined the laboratory of Dr. William G. Kaelin, Jr. at the Dana-Farber Cancer Institute and Harvard Medical School as an American Cancer Society Postdoctoral Fellow. During his time in the Kaelin Laboratory, he studied metabolic reprogramming in glioma and developed new strategies for brain tumor therapy. In 2019, Dr. McBrayer joined the faculty of Children's Medical Center Research Institute at UT Southwestern as an Assistant Professor and CPRIT Scholar in Cancer Research. Since then, he has received awards from the National Institutes of Health, the Cancer Prevention and Research Institute of Texas, and others. The McBrayer Lab is working to understand the roles that metabolites play as signaling molecules. Metabolite signaling is critical for proper development and tumor suppression because mutations in metabolic genes that disrupt this process can cause developmental disorders or tumor formation. Work in the McBrayer Lab seeks to reveal how regulation or dysregulation of key metabolites shapes cell fate, influences cell function, and creates therapeutic opportunities to treat genetic diseases and cancer. By creating experimental tools that provide new perspectives on metabolite signaling, the McBrayer Lab addresses several fundamental biological questions. How do metabolic alterations affect the epigenome in development and disease? How do metabolites mediate cell-cell communication? How can we leverage insights into metabolite signaling to improve treatment of inborn errors of metabolism and brain tumors? Education Undergraduate Baylor University (2006), Biochemistry Graduate School Northwestern Univ (2012), Cancer Biology Research Interest Biochemistry Brain Tumor Biology Cancer Biology Metabolism Mouse Genetics Publications Featured Publications Vorasidenib improves response to subsequent chemoradiation in a genetically engineered mouse model of IDH-mutant glioma. Shi DD, Calvo Fernández E, Puliyappadamba VT, Lanman TA, Xiao Y, Wen Z, Minor M, Prost D, Lasica AB, Cai F, Neumann E, Gudipelly S, Clark LM, Nguyen QD, Peña S, Wansapura J, Kaphle P, Shipman T, Levitt MM, Lin MD, Tsai AC, Lee JH, Cahill DP, Rahman R, Haas-Kogan DA, Richardson TE, Tirosh I, Jain P, Tron AE, Nakhate V, Youssef G, Dehais C, Jacob J, Reardon DA, Miller JJ, Abdullah KG, Wen PY, DeBerardinis RJ, Xu L, Touat M, Peters KB, Gonzalez Castro LN, Kaelin WG, Suvà ML, McBrayer SK, Sci Transl Med 2026 Aug 18 861 eaee5876 A transcriptional biosensor reveals mechanisms of α-ketoglutarate signaling to chromatin. Sternisha AC, Li H, Gajendra K, Xiao Y, Zhao X, Traylor JI, Guo L, Jun JH, Fleishman M, Shipman T, Puliyappadamba VT, Kaphle P, Ouyang Q, Schmidt M, Shi DD, Savani MR, Tsai AC, Lee JH, Gordillo R, Garcia-Bermudez J, Kim YJ, Tso SC, Brautigam CA, Zacharias LG, Mathews TP, Xu L, Doench JG, Koduri V, Abdullah KG, Agathocleous M, Banaszynski LA, DeBerardinis RJ, Morrow EM, McBrayer SK, Science 2026 Jul 393 6808 eadx8675 Nitrogen metabolism profiling reveals cell state-specific pyrimidine synthesis pathway choice. Savani MR, Li B, Smith BC, Gu W, Xiao Y, Baquer G, Shipman T, Oken SS, Manoj N, Zacharias LG, Puliyappadamba VT, Stopka SA, Regan MS, Levitt MM, Edgar CK, Hicks WH, Anand S, Martin-Sandoval MS, Winston R, S Patrício J, Johnson X, Tippetts TS, Shi DD, Lemoff A, Richardson TE, Zinn PO, Solmonson A, Mathews TP, Agar NYR, DeBerardinis RJ, Abdullah KG, McBrayer SK, Nat Metab 2026 Apr KDM6 Enzymes are the Mechanistic Targets of Mutant IDH that Dictate Replication Stress Sensitivity. Tsai AC, Lin MD, Puliyappadamba VT, Junginger DM, Donovan VG, Kaplan EG, Drepanos LM, Wakimoto H, Cahill DP, Losman JA, Mouw KW, Abdullah KG, Doench JG, Nash D, Vitt D, Gege C, Kohlhof H, McBrayer SK, Kaelin WG, Shi DD, bioRxiv 2026 Apr Stable isotope tracing in human plasma-like medium reveals metabolic and immune modulation of the glioblastoma microenvironment. Savani MR, El Shami M, Miki K, Gattie LC, Smith BC, Hicks WH, Weiss JO, Oken SS, Katta LN, Shipman T, Ghoche MT, Zacharias LG, Martin-Sandoval MS, Montgomery EY, Xiao Y, Shi DD, Rich JN, Richardson TE, Zinn PO, Lega BC, Mathews TP, DeBerardinis RJ, Abdullah KG, McBrayer SK, Neuro Oncol 2025 Oct Mutant IDH silences GSX2 to reprogram neural progenitor cell fate and promote gliomagenesis. Xiao Y, Shi DD, Guo L, Neumann E, Levitt MM, Kaphle P, Shipman T, Li H, Cai F, Ramirez DMO, Zacharias LG, Chen Z, Lin M, Puliyappadamba VT, Chen T, Savani MR, Peña S, Wansapura J, Mathews TP, Mishra P, Kim YJ, Raj P, Richardson TE, Xu J, Mack SC, Rahme GJ, Bernstein BE, DeBerardinis RJ, Tirosh I, Suvà ML, Xu L, Abdullah KG, McBrayer SK, bioRxiv 2025 Aug Mutant IDH1 inhibition induces dsDNA sensing to activate tumor immunity. Wu MJ, Kondo H, Kammula AV, Shi L, Xiao Y, Dhiab S, Xu Q, Slater CJ, Avila OI, Merritt J, Kato H, Kattel P, Sussman J, Gritti I, Eccleston J, Sun Y, Cho HM, Olander K, Katsuda T, Shi DD, Savani MR, Smith BC, Cleary JM, Mostoslavsky R, Vijay V, Kitagawa Y, Wakimoto H, Jenkins RW, Yates KB, Paik J, Tassinari A, Saatcioglu DH, Tron AE, Haas W, Cahill D, McBrayer SK, Manguso RT, Bardeesy N, Science 2024 Jul 385 6705 eadl6173 Discovery and Optimization of N-Arylated Tetracyclic Dicarboximides That Target Primary Glioma Stem-like Cells. Wang HY, Nguyen TP, Sternisha AC, Carroll CL, Cross B, Morlock L, Williams NS, McBrayer S, Nijhawan D, De Brabander JK, J Med Chem 2024 May Protocol to establish a genetically engineered mouse model of IDH1-mutant astrocytoma. Shi DD, Lee JH, Wang AC, Khanal J, Gao W, Kaelin WG, McBrayer SK, STAR Protoc 2023 May 4 2 102281 Selective and brain-penetrant lanosterol synthase inhibitors target glioma stem-like cells by inducing 24(S),25-epoxycholesterol production. Nguyen TP, Wang W, Sternisha AC, Corley CD, Wang HL, Wang X, Ortiz F, Lim SK, Abdullah KG, Parada LF, Williams NS, McBrayer SK, McDonald JG, De Brabander JK, Nijhawan D, Cell Chem Biol 2023 Feb 30 2 214-229.e18 Results 1-10 of 43 1 2 3 4 5 Next Last Honors & Awards Distinguished Scientist Award, Sontag Foundation (2021) Rising Stars of Cancer Metabolism Runner-Up, New York Academy of Sciences (2021) Abeloff V Scholar Award, V Foundation for Cancer Research (2020) NCI K22 Career Transition Award (2019) Cancer Prevention and Research Institute of Texas (CPRIT) Scholar (2018) Cold Spring Harbor Laboratory Young Scholars Symposium (2018) Aspen Cancer Conference Fellow (2017) Harvard Cancer Center Brain SPORE Career Enhancement Program Award (2017) American Cancer Society Postdoctoral Fellowship (2014) NCI T32 Fellowship (2008) Magna Cum Laude, Baylor University (2006) Phi Beta Kappa (2006) Professional Associations/Affiliations American Association for Cancer Research (2021) Children's Medical Center Research Institute at UT Southwestern (2019) Harold C. Simmons Comprehensive Cancer Center (2019) Peter O'Donnell Jr. Brain Institute (2022) Society for Neuro-Oncology (2021)
