Samuel McBrayer, Ph.D.

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. Since then, he has received awards from the National Cancer Institute and the Cancer Prevention and Research Institute of Texas.

The McBrayer laboratory is working to identify the metabolic mechanisms that push cells to become cancerous and find new ways to inhibit them. To identify these mechanisms, they study the biology of brain tumors driven by mutations in genes that regulate metabolism. Studying these mutations will help them discover fundamental connections between metabolism and other aspects of cell biology that are likely to control cancer formation in many different tissues. These insights hold great promise for the development of new therapies for patients with brain tumors and, by extension, for those with other types of cancer.

Undergraduate

Baylor University (2006), Biochemistry

Graduate School

Northwestern Univ (2012), Cancer Biology

• Biochemistry
• Brain Tumor Biology
• Cancer Biology
• Metabolism
• Mouse Genetics

Featured Publications

Isocitrate dehydrogenase (IDH) mutant gliomas: A Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions.

Miller JJ, Gonzalez Castro LN, McBrayer S, Weller M, Cloughesy T, Portnow J, Andronesi O, Barnholtz-Sloan JS, Baumert BG, Berger MS, Bi WL, Bindra R, Cahill DP, Chang SM, Costello JF, Horbinski C, Huang RY, Jenkins RB, Ligon KL, Mellinghoff IK, Nabors LB, Platten M, Reardon DA, Shi DD, Schiff D, Wick W, Yan H, von Deimling A, van den Bent M, Kaelin WG, Wen PY, Neuro Oncol 2022 Oct

Oncometabolite d-2HG alters T cell metabolism to impair CD8⁺ T cell function.

Notarangelo G, Spinelli JB, Perez EM, Baker GJ, Kurmi K, Elia I, Stopka SA, Baquer G, Lin JR, Golby AJ, Joshi S, Baron HF, Drijvers JM, Georgiev P, Ringel AE, Zaganjor E, McBrayer SK, Sorger PK, Sharpe AH, Wucherpfennig KW, Santagata S, Agar NYR, Suvà ML, Haigis MC, Science 2022 Sep 377 6614 1519-1529

A druggable addiction to de novo pyrimidine biosynthesis in diffuse midline glioma.

Pal S, Kaplan JP, Nguyen H, Stopka SA, Savani MR, Regan MS, Nguyen QD, Jones KL, Moreau LA, Peng J, Dipiazza MG, Perciaccante AJ, Zhu X, Hunsel BR, Liu KX, Alexandrescu S, Drissi R, Filbin MG, McBrayer SK, Agar NYR, Chowdhury D, Haas-Kogan DA, Cancer Cell 2022 Aug

De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma.

Shi DD, Savani MR, Levitt MM, Wang AC, Endress JE, Bird CE, Buehler J, Stopka SA, Regan MS, Lin YF, Puliyappadamba VT, Gao W, Khanal J, Evans L, Lee JH, Guo L, Xiao Y, Xu M, Huang B, Jennings RB, Bonal DM, Martin-Sandoval MS, Dang T, Gattie LC, Cameron AB, Lee S, Asara JM, Kornblum HI, Mak TW, Looper RE, Nguyen QD, Signoretti S, Gradl S, Sutter A, Jeffers M, Janzer A, Lehrman MA, Zacharias LG, Mathews TP, Losman JA, Richardson TE, Cahill DP, DeBerardinis RJ, Ligon KL, Xu L, Ly P, Agar NYR, Abdullah KG, Harris IS, Kaelin WG, McBrayer SK, Cancer Cell 2022 Aug

EGFR ligand shifts the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastoma by suppressing invasion through BIN3 upregulation.

Guo G, Gong K, Beckley N, Zhang Y, Yang X, Chkheidze R, Hatanpaa KJ, Garzon-Muvdi T, Koduru P, Nayab A, Jenks J, Sathe AA, Liu Y, Xing C, Wu SY, Chiang CM, Mukherjee B, Burma S, Wohlfeld B, Patel T, Mickey B, Abdullah K, Youssef M, Pan E, Gerber DE, Tian S, Sarkaria JN, McBrayer SK, Zhao D, Habib AA, Nat Cell Biol 2022 Aug 24 8 1291-1305

Establishment of patient-derived organoid models of lower grade glioma.

Abdullah KG, Bird CE, Buehler JD, Gattie LC, Savani MR, Sternisha AC, Xiao Y, Levitt MM, Hicks WH, Li W, Ramirez DMO, Patel T, Garzon-Muvdi T, Barnett S, Zhang G, Ashley DM, Hatanpaa KJ, Richardson TE, McBrayer SK, Neuro Oncol 2021 Nov

Peptidic degron for IMiD-induced degradation of heterologous proteins.

Koduri V, McBrayer SK, Liberzon E, Wang AC, Briggs KJ, Cho H, Kaelin WG, Proc. Natl. Acad. Sci. U.S.A. 2019 02 116 7 2539-2544

A Phase Ib Trial of CB-839 (Telaglenastat) in Combination with Radiation Therapy and Temozolomide in Patients with IDH-Mutated Diffuse Astrocytoma and Anaplastic Astrocytoma (NCT03528642).

Kizilbash SH, McBrayer SK, Port J, Reid JM, Lanza I, Allred JB, Chakravarti A, Kunos C, Adjei AA, Journal of Clinical Oncology 2019 15 Supplement. 37

Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma.

McBrayer SK, Mayers JR, DiNatale GJ, Shi DD, Khanal J, Chakraborty AA, Sarosiek KA, Briggs KJ, Robbins AK, Sewastianik T, Shareef SJ, Olenchock BA, Parker SJ, Tateishi K, Spinelli JB, Islam M, Haigis MC, Looper RE, Ligon KL, Bernstein BE, Carrasco RD, Cahill DP, Asara JM, Metallo CM, Yennawar NH, Vander Heiden MG, Kaelin WG, Cell 2018 09 175 1 101-116.e25

Autochthonous tumors driven by Rb1 loss have an ongoing requirement for the RBP2 histone demethylase.

McBrayer SK, Olenchock BA, DiNatale GJ, Shi DD, Khanal J, Jennings RB, Novak JS, Oser MG, Robbins AK, Modiste R, Bonal D, Moslehi J, Bronson RT, Neuberg D, Nguyen QD, Signoretti S, Losman JA, Kaelin WG, Proc. Natl. Acad. Sci. U.S.A. 2018 04 115 16 E3741-E3748

• 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)
• Cold Spring Harbor Laboratory Young Scholars Symposium
  (2018)
• CPRIT Scholar in Cancer Research
  (2018)
• Aspen Cancer Conference Fellow
  (2017)
• DF/HCC Brain SPORE Career Enhancement Program Award
  (2017)
• American Cancer Society Postdoctoral Fellowship
  (2014)
• Katten Muchin Rosenman, LLP Scholarship
  (2011)
• NCI T32 Fellowship
  (2008)
• Magna Cum Laude, Baylor University
  (2006)
• Phi Beta Kappa
  (2006)

• American Association for Cancer Research (2021)
• Simmons Comprehensive Cancer Center (2019)
• Society for Neuro-Oncology (2021)