What are gliomas, and why is this glioma brain tumor research important?
Gliomas are a type of brain tumor that occurs when normal cells in the brain become abnormal and grow uncontrollably. They are the most common type of brain tumor and can be very difficult to treat. The most prevalent type of glioma, glioblastoma, is especially challenging because it is highly aggressive and often resists treatment.
Despite our best efforts with surgery, chemotherapy, and radiation, glioblastomas often relapse. One reason for this is that each tumor is unique, and even within a single tumor, different cells can have different mutations. Another challenge is that cancer cells in glioblastomas interact with normal cells in the brain in ways that make them harder to kill. This makes it very difficult to find an effective treatment that works for everyone. We need new approaches that can attack different types of cells within the tumor, and we need to understand the complex nature of these tumors better.
In the Al-Holou lab, our research is focused on understanding how brain cancer stem cells interact with normal brain cells and immune cells in the brain tumor microenvironment. To achieve this, we utilize cutting-edge spatial and single-cell sequencing technology to study individual cells and their interactions within tumors, and then model these interactions. By studying these complex interactions, we can uncover the mechanisms that drive aggressive tumor behavior and identify potential vulnerabilities that can be targeted to develop novel ground-breaking treatments for these life-threatening neoplasms.
Publications
2023
Subclonal evolution and expansion of spatially distinct THY1-positive cells is associated with recurrence in glioblastoma
Al-Holou, W. N., Wang, H., Ravikumar, V., Shankar, S., Oneka, M., Fehmi, Z., Verhaak, R. G., Kim, H., Pratt, D., Camelo-Piragua, S., Speers, C., Wahl, D. R., Hollon, T., Sagher, O., Heth, J. A., Muraszko, K. M., Lawrence, T. S., de Carvalho, A. C., Mikkelsen, T., Rao, A., Rehemtulla, A.
Neoplasia. 2023 Jan 6.
doi: 10.1016/j.neo.2022.100872
2022
Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression.
Comba A, Faisal SM, Dunn PJ, Argento AE, Hollon TC, Al-Holou WN, Varela ML, Zamler DB, Quass GL, Apostolides PF, Abel C 2nd, Brown CE, Kish PE, Kahana A, Kleer CG, Motsch S, Castro MG, Lowenstein PR.
Nat Commun. 2022 Jun 24;13(1):3606.
doi: 10.1038/s41467-022-31340-1
Rapid Automated Analysis of Skull Base Tumor Specimens Using Intraoperative Optical Imaging and Artificial Intelligence.
Jiang C, Bhattacharya A, Linzey JR, Joshi RS, Cha SJ, Srinivasan S, Alber D, Kondepudi A, Urias E, Pandian B, Al-Holou WN, Sullivan SE, Thompson BG, Heth JA, Freudiger CW, Khalsa SSS, Pacione DR, Golfinos JG, Camelo-Piragua S, Orringer DA, Lee H, Hollon TC.
Neurosurgery. 2022 Mar 30.
doi: 10.1227/neu.0000000000001929
Circumferential sulcus-guided resection technique for improved outcomes of low-grade gliomas.
Al-Holou WN, Suki D, Hodges TR, Everson RG, Freeman J, Ferguson SD, McCutcheon IE, Prabhu SS, Weinberg JS, Sawaya R, Lang FF.
J Neurosurg. 2022 Jan 7:1-11.
2021
G-CSF secreted by mutant IDH1 glioma stem cells abolishes myeloid cell immunosuppression and enhances the efficacy of immunotherapy.
Alghamri MS, McClellan BL, Avvari RP, Thalla R, Carney S, Hartlage MS, Haase S, Ventosa M, Taher A, Kamran N, Zhang L, Faisal SM, Núñez FJ, Garcia-Fabiani MB, Al-Holou WN, Orringer D, Hervey-Jumper S, Heth J, Patil PG, Eddy K, Merajver SD, Ulintz PJ, Welch J, Gao C, Liu J, Núñez G, Hambardzumyan D, Lowenstein PR, Castro MG.
Sci Adv. 2021 Oct;7(40):eabh3243.
Uncovering Spatiotemporal Heterogeneity of High-Grade Gliomas: From Disease Biology to Therapeutic Implications
Comba Andrea, Faisal Syed M., Varela Maria Luisa, Hollon Todd, Al-Holou Wajd N., Umemura Yoshie, Nunez Felipe J., Motsch Sebastien, Castro Maria G., Lowenstein Pedro R.
Front. Oncol., 05 Aug 2021
A Phase 2 Study of Dose-intensified Chemoradiation Using Biologically Based Target Volume Definition in Patients With Newly Diagnosed Glioblastoma.
Kim MM, Sun Y, Aryal MP, Parmar HA, Piert M, Rosen B, Mayo CS, Balter JM, Schipper M, Gabel N, Briceño EM, You D, Heth J, Al-Holou W, Umemura Y, Leung D, Junck L, Wahl DR, Lawrence TS, Cao Y.
Int J Radiat Oncol Biol Phys. 2021 Jul 1;110(3):792-803.
doi: 10.1016/j.ijrobp.2021.01.033
Stem cells for the treatment of glioblastoma: a 20-year perspective.
Calinescu AA, Kauss MC, Sultan Z, Al-Holou WN, O'Shea SK.
CNS Oncol. 2021 May 19:CNS73.
2020
A validated integrated clinical and molecular glioblastoma long-term survival-predictive nomogram.
Ferguson SD, Hodges TR, Majd NK, Alfaro-Munoz K, Al-Holou WN, Suki D, de Groot JF, Fuller GN, Xue L, Li M, Jacobs C, Rao G, Colen RR, Xiu J, Verhaak R, Spetzler D, Khasraw M, Sawaya R, Long JP, Heimberger AB.
Neurooncol Adv. 2020 Oct 31;3(1):vdaa146.
H3K27M-mutant diffuse midline glioma with extensive intratumoral microthrombi in a young adult with COVID-19-associated coagulopathy.
Pun M, Haggerty-Skeans J, Pratt D, Fudym Y, Al-Holou WN, Camelo-Piragua S, Venneti S.
Acta Neuropathol. 2020 Aug;140(2):227-229.
DOI: 10.1007/s00401-020-02184-0
Rapid, label-free detection of diffuse glioma recurrence using intraoperative stimulated Raman histology and deep neural networks.
Hollon TC, Pandian B, Urias E, Save AV, Adapa AR, Srinivasan S, Jairath NK, Farooq Z, Marie T, Al-Holou WN, Eddy K, Heth JA, Khalsa SSS, Conway K, Sagher O, Bruce JN, Canoll P, Freudiger CW, Camelo-Piragua S, Lee H, Orringer DA.
Neuro Oncol. 2020 Jul 16:noaa162.
Perilesional Resection of Glioblastoma Is Independently Associated With Improved Outcomes.
Al-Holou WN, Hodges TR, Everson RG, Freeman J, Zhou S, Suki D, Rao G, Ferguson SD, Heimberger AB, McCutcheon IE, Prabhu SS, Lang FF, Weinberg JS, Wildrick DM, Sawaya R.
Neurosurgery. 2020 Jan 1;86(1):112-121.