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Sam McBrayer Lab

Research Focus

Alterations in whole-body metabolism, such as those that occur in obesity or diabetes, can increase the risk of developing certain forms of cancer. These findings indicate that external metabolic cues can trigger cancer formation and growth at the cellular level. However, we have limited knowledge of the internal metabolic changes that influence whether a cell becomes cancerous or not.

Our goal is to identify the metabolic mechanisms that push cells to become cancerous and find new ways to inhibit them. To identify these mechanisms, we study the biology of brain tumors driven by mutations in genes that regulate metabolism. Studying these mutations will help us 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.

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….
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Research Projects

Select Publications

Shi, D.D., Lee, J.H., Wang, A.C., Khanal, J., Gao, W., Kaelin, W.G. Jr., and S.K. McBrayer. (2023). Protocol to establish a genetically engineered mouse model of IDH1-mutant astrocytoma. STAR Protocols Epub ahead of print. (PubMed)

Miller, J.J., Gonzalez Castro, L.N., McBrayer, S.K., Weller, M., Cloughesy, T., Portnow, J., Andronesi, O., Barnholtz-Sloan, J.S., Baumert, B.G., Berger, M.S., Bi, W.L., Bindra, R., Cahill, D.P., Chang, S.M., Costello, J.F., Horbinski, C., Huang, R.Y., Jenkins, R.B., Ligon, K.L., Mellinghoff, I.K., Nabors, L.B., Platten, M., Reardon, D.A., Shi, D.D., Schiff, D., Wick, W., Yan, H., von Deimling, A., van den Bent, M., Kaelin, W.G., and P.Y. Wen. (2022). Isocitrate dehydrogenase (IDH) mutant gliomas: A Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions. Neuro Oncology 25, 4-25. (PubMed)

Notarangelo, G., Spinelli, J.B., Perez, E.M., Baker, G.J., Kurmi, K., Elia, I., Stopka, S.A., Baquer, G., Lin, J.R., Golby, A..J, Joshi, S., Baron, H.F., Drijvers, J.M., Georgiev, P., Ringel, A.E., Zaganjor, E., McBrayer, S.K., Sorger, P.K., Sharpe, A.H., Wucherpfennig, K.W., Santagata, S., Agar, N.Y.R., Suvà, M.L., and M.C. Haigis. (2022). Oncometabolite d-2HG alters T cell metabolism to impair CD8+ T cell function. Science 377, 1519-1529. (PubMed)

Pal, S., Kaplan, J.P., Nguyen, H., Stopka, S.A., Savani, M.R., Regan, M.S., Nguyen, Q.D., Jones, K.L., Moreau, L.A., Peng, J., Dipiazza, M.G., Perciaccante, A.J., Zhu, X., Hunsel, B.R., Liu, K.X., Alexandrescu, S., Drissi, R., Filbin, M.G., McBrayer, S.K., Agar, N.Y.R., Chowdhury, D., and D.A. Haas-Kogan. (2022). A druggable addiction to de novo pyrimidine biosynthesis in diffuse midline glioma. Cancer Cell 40, 957-972. (PubMed)

Shi, D.D., Savani, M.R., Levitt, M.M., Wang, A.C., Endress, J.E., Bird, C.E., Buehler, J., Stopka, S.A., Regan, M.S., Lin, Y.F., Puliyappadamba, V.T., Gao, W., Khanal, J., Evans, L., Lee, J.H., Guo, L., Xiao, Y., Xu, M., Huang, B., Jennings, R.B., Bonal, D.M., Martin-Sandoval, M.S., Dang, T., Gattie, L.C., Cameron, A.B., Lee, S., Asara, J.M., Kornblum, H.I., Mak, T.W., Looper, R.E., Nguyen, Q.D., Signoretti, S., Gradl, S., Sutter, A., Jeffers, M., Janzer, A., Lehrman, M.A., Zacharias, L.G., Mathews, T.P., Losman, J.A., Richardson, T.E., Cahill, D.P., DeBerardinis, R.J., Ligon, K.L., Xu, L., Ly, P., Agar, N.Y.R., Abdullah, K.G., Harris, I.S., Kaelin, W.G. Jr, and S.K. McBrayer. (2022). De novo pyrimidine synthesis is a targetable vulnerability in IDH mutant glioma. Cancer Cell 40, 939-956. (PubMed)

Guo, G., Gong, K., Beckley, N., Zhang, Y., Yang, X., Chkheidze, R., Hatanpaa, K.J., Garzon-Muvdi, T., Koduru, P., Nayab, A., Jenks, J., Sathe, A.A., Liu, Y., Xing, C., Wu, S.Y., Chiang, C.M., Mukherjee, B., Burma, S., Wohlfeld, B., Patel, T., Mickey, B., Abdullah, K., Youssef, M., Pan, E., Gerber, D.E., Tian, S., Sarkaria, J.N., McBrayer, S.K., Zhao, D., and A.A. Habib. (2022). EGFR ligand shifts the role of EGFR from oncogene to tumour suppressor in EGFR-amplified glioblastoma by suppressing invasion through BIN3 upregulation. Nature Cell Biology 24, 1291-1305. (PubMed)

Abdullah, K.G., Bird, C.E., Buehler, J.D., Gattie, L.C., Savani, M.R., Sternisha, A.C., Xiao, Y., Levitt, M.M., Hicks, W.H., Li, W., Ramirez, D.M.O., Patel, T., Garzon-Muvdi, T., Barnett, S., Zhang, G., Ashley, D.M., Hatanpaa, K.J., Richardson, T.E., and S.K. McBrayer. (2022). Establishment of patient-derived organoid models of lower-grade glioma. Neuro Oncology 24, 612-623. (PubMed)

Koduri, V., McBrayer, S.K., Liberzon, E., Wang, A.C., Briggs, K.J., Cho, H., and W.G. Kaelin. (2019). Peptidic Degron for IMiD-Induced Degradation of Heterologous Proteins. PNAS 116, 2539-2544. (PubMed)

McBrayer, S.K., Mayers, J.R., DiNatale, G.J., Shi, D.D., Khanal, J., Chakraborty, A.A., Sarosiek, K.A., Briggs, K.J., Robbins, A.K., Sewastianik, T., Shareef, S.J., Olenchock, B.A., Parker, S.J., Tateishi, K., Spinelli, J.B., Islam, M., Haigis, M.C., Looper, R.E., Ligon, K.L., Bernstein, B.E., Carrasco, R.D., Cahill, D.P., Asara, J.M., Metallo, C.M., Yennawar, N.H., Vander-Heiden, M.G., and W.G. Kaelin. (2018). Transaminase Inhibition by 2-Hydroxyglutarate Impairs Glutamate Biosynthesis and Redox Homeostasis in Glioma. Cell 175, 101-116. (PubMed)

McBrayer, S.K., Olenchock, B.A., DiNatale, G.J., Shi, D.D., Khanal, J., Jennings, R.B., Novak, J.S., Oser, M.G., Robbins, A.K., Modiste, R., Bonal, D., Moslehi, J., Bronson, R.T., Neuberg, D., Nguyen, Q.D., Signoretti, S., Losman, J.A., and W.G. Kaelin. (2018). Autochthonous Tumors Driven by Rb1 Loss Have an Ongoing Requirement for the RBP2 Histone Demethylase. PNAS 115, E3741-E3748.  (PubMed)

Lab Members

Eric Montgomery

Medical Student, UT Southwestern Medical School
Medical Student (2020-2022)

Bailey Smith

Harvard Medical School (Pathways M.D. Program), Class of 2028
Research Technician

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