Research Area
1) MEDULLOBLASTOMA Identify druggable targets that work in combination with Bmi1 inhibition to decrease MB progression and spinal dissemination in our therapy adapted patient-derived xenograft (PDX) model of MB recurrence. Describe the role of BPIFB4 as a potent regulator of self-renewal and specific driver of MB relapse. 2) GLIOBLASTOMA: Preclinical development and evaluation of CAR-T cells targeting CD133 (BTIC marker). Preclinical development and evaluation of CAR-T cells targeting CD70. CRISPR-Cas9 genetic screening to identify targets that act to increase sensitivity of GBM cells to current treatment options. 3) BRAIN METASTASIS Identification of novel genes that regulate the formation of brain metastasis. Functional genomics to characterization the pre- to micro-metastatic states in brain metastasis. Identification of candidate drugs that could target the brain metastatic process, especially those with the potential to translate into the clinic as preventative therapy for pri
Team Description
These are the passionate and dedicated individuals that are the face, the heart, the brain, and the soul of the Sheila Singh Lab. They work tirelessly, inspired by the lives of patients. And, together, their efforts are expanding the frontiers of brain cancer research.
Team Members
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Publications
1. William D. Gwynne, Yujin Suk, Stefan Custers, Nicholas Mikolajewicz, Jeremy K. Chan, Zsolt Zador, Shawn C. Chafe, Kui Zhai, Laura Escudero, Cunjie Zhang, Olga Zaslaver, Chirayu Chokshi, Muhammad Vaseem Shaikh, David Bakhshinyan, Ian Burns, Iqra Chaudhry, Omri Nachmani, Daniel Mobilio, William T. Maich, Patricia Mero, Kevin R. Brown, Andrew T. Quaile, Chitra Venugopal, Jason Moffat, J. Rafael Montenegro-Burke, Sheila K. Singh. Cancer-selective metabolic vulnerabilities in MYC-amplified medulloblastoma. Cancer Cell, 2022, ISSN 1535-6108. https://doi.org/10.1016/j.ccell.2022.10.009.
2. Bassey-Archibong BI, Chokshi CR, Aghaei N, Kieliszek AM, Tatari N, McKenna D, Singh MS, Subapanditha MK, Parmar A, Savage N2, Lam F, Tokar T, Jurisica I, Provias J, Lu Y, Venugopal C, Singh SK. Identification of an HLA-G/SPAG9/STAT3 axis presents a novel targetable liability in early brain metastases. PNAS Proc Natl Acad Sci U S A. 2023 Feb 21;120(8):e2205247120. doi: 10.1073/pnas.2205247120. Epub 2023 Feb 13.
3. Michelle M Kameda-Smith; Helen Zhu; EnChing Luo; Chitra Venugopal; Agata Xella; Kevin Brown; Raymond G Fox; Brian Yee; Sansi Xing; Frederick Tan; David Bakhshinyan; Ashley A Adile; Minomi Subapanditha; Daniel Picard; Jason Moffat; Adam Fleming; Kristin Hope; John P Provias; Marc Remke; Yu Lu; Tannishtha Reya; Jüri Reimand; Robert J Wechsler-Reya; Gene W Yeo; Sheila Kumari Singh. Characterization of an RNA binding protein interactome reveals the targetable post-transcriptional landscape of MYC-amplified medulloblastoma. Nature Communications 2022 Dec 6;13(1):7506. doi: 10.1038/s41467-022-35118-3.PMID: 36473869.
4. Parvez Vora, Chitra Venugopal, Sabra Salim, Emily Ford, Mathieu Seyfrid, Maleeha Qazi, Ashley Adile, Kevin Brown, Ryan Wylie, Dillon McKenna, James Jonathan Bramson, Kristin Hope, Jason Moffat, Sheila K. Singh. The Rational Development of CD133-Targeting Immunotherapies for Glioblastoma [published online ahead of print, 2020 May 22]. Cell Stem Cell. 2020 ;S1934-5909(20)30147-8. doi:10.1016/j.stem.2020.04.008
5. Branavan Manoranjan, Chitra Venugopal, Anna Dvorkin-Gheva, Steven Moreira, Michelle M. Kameda- Smith, Minomi Subapanditha, Robin Hallett, David Bakhshinyan, Neil Savage, Ashley Adile, Blake Yarascavitch, Olufemi Ajani, Adam Fleming, Bradley W. Doble, Sheila K. Singh. Wnt activation is a therapeutic strategy in medulloblastoma. Nature Communications (August 28 2020)11:4323 https://doi.org/10.1038/s41467-020-17953-4
6. Qazi M, Bakhshinyan D, Singh SK. Deciphering brain tumor heterogeneity, one cell at a time. Nature Medicine. Nat Med. 2019 Oct;25(10):1474-1476.
7. Bakhshinyan D, Adile AA, Liu J, Gwynne WD, Suk Y, Custers S, Burns I, Singh M, McFarlane N, Subapanditha MK, Qazi MA, Vora P, Kameda-Smith MM, Savage N, Desmond KL, Tatari N, Tran D, Seyfrid M, Hope K, Bock NA, Venugopal C, Bader GD, Singh SK. Temporal profiling of therapy resistance in human medulloblastoma identifies novel targetable drivers of recurrence. Science Advances. 2021 Dec 10;7(50):eabi5568. doi: 10.1126/sciadv.abi5568. Epub 2021 Dec 8. PMID: 34878832; PMCID: PMC8654291.
8. Seyfrid M, Maich WT, Shaikh VM, Tatari N, Upreti D, Piyasena D, Subapanditha M, Savage N, McKenna D, Mikolajewicz N, Han H, Chokshi C, Kuhlmann L, Khoo A, Salim SK, Archibong-Bassey B, Gwynne W, Brown K, Murtaza N, Bakhshinyan D, Vora P, Venugopal C, Moffat J, Kislinger T, Singh S. CD70 as an actionable immunotherapeutic target in recurrent glioblastoma and its microenvironment. J Immunother Cancer (JITC, IF 14.7). 2022 Jan;10(1):e003289. doi: 10.1136/jitc-2021-003289.
9. Maleeha A. Qazi, Sabra K. Salim, Kevin Brown , Neil Savage, Nicholas Mickolajewicz, Hong Han, Minomi K. Subapanditha, David Bakhshinyan, Allison Nixon, Parvez Vora, Kimberly Desmond, Chirayu Chokshi, Mohini Singh, Amanda Khoo, Andrew Macklin, Shahbaz Khan, Nazanin Tatari, Neil Winegarden, Trevor Pugh, Nicholas Bock, Alireza Mansouri, Chitra Venugopal, Thomas Kislinger, Sidhartha Goyal, Jason Moffat*, Sheila K. Singh*. Characterization of the minimal residual disease state reveals distinct evolutionary trajectories of human glioblastoma. Cell Reports 2022 Sep 27;40(13):111420. doi: 10.1016/j.celrep.2022.111420.PMID: 36170831
10. Vora P, Seyfrid M, Venugopal C, Qazi MA, Salim S, Isserlin R, Subapanditha M, O'Farrell E, Mahendram S, Singh M, Bakhshinyan D, Chokshi C, McFarlane N, Dvorkin-Gheva A, Brown KR, Murty N, Moffat J, Bader GD, Singh SK. Bmi1 regulates human glioblastoma stem cells through activation of differential gene networks in CD133+ brain tumor initiating cells. J Neurooncol. 2019 Jul;143(3):417-428
11. Bakhshinyan D, Venugopal C, Adile AA, Garg N, Manoranjan B, Hallett R, Wang X, Mahendram S, Vora P, Vijayakumar T, Subapanditha M, Singh M, Kameda-Smith MM, Qazi M, McFarlane N, Mann A, Ajani OA, Yarascavitch B, Ramaswamy V, Farooq H, Morrissy S, Cao L, Sydorenko N, Baiazitov R, Du W, Sheedy J, Weetall M, Moon YC, Lee CS, Kwiecien JM, Delaney KH, Doble B, Cho YJ, Mitra S, Kaplan D, Taylor MD, Davis TW, Singh SK. BMI1 is a therapeutic target in recurrent medulloblastoma. Oncogene. 2019 Mar;38(10):1702-1716.
12. Singh M, Venugopal C, Tokar T, McFarlane N, Subapanditha MK, Qazi M, Bakhshinyan D, Vora P, Murty NK, Jurisica I, Singh SK. Therapeutic Targeting of the Premetastatic Stage in Human Lung-to-Brain Metastasis. Cancer Res. 2018 Sep 1;78(17):5124-5134.
13. Qazi MA, Vora P, Venugopal C, Adams J, Singh M, Hu A, Gorelik M, Subapanditha MK, Savage N, Yang J, Chokshi C, London M, Gont A, Bobrowski D, Grinshtein N, Brown KR, Murty NK, Nilvebrant J, Kaplan D, Moffat J, Sidhu S, Singh SK. Cotargeting Ephrin Receptor Tyrosine Kinases A2 and A3 in Cancer Stem Cells Reduces Growth of Recurrent Glioblastoma. Cancer Res. 2018 Sep 1;78(17):5023-5037.
14. Singh M, Bakhshinyan D, Venugopal C, Singh SK. Preclinical Modeling and Therapeutic Avenues for Cancer Metastasis to the Central Nervous System. Front Oncol. 2017 Sep 19;7:220.
15. Singh M, Venugopal C, Tokar T, Brown KR, McFarlane N, Bakhshinyan D, Vijayakumar T, Manoranjan B, Mahendram S, Vora P, Qazi M, Dhillon M, Tong A, Durrer K, Murty N, Hallet R, Hassell JA, Kaplan DR, Cutz JC, Jurisica I, Moffat J, Singh SK. RNAi screen identifies essential regulators of human brain metastasis-initiating cells. Acta Neuropathol. 2017 Dec;134(6):923-940.
16. Qazi MA, Vora P, Venugopal C, McFarlane N, Subapanditha MK, Murty NK, Hassell JA, Hallett RM, Singh SK. A novel stem cell culture model of recurrent glioblastoma. J Neurooncol. 2016 Jan;126(1):57-67.
17. Venugopal C, Hallett R, Vora P, Manoranjan B, Mahendram S, Qazi MA, McFarlane N, Subapanditha M, Nolte SM, Singh M, Bakhshinyan D, Garg N, Vijayakumar T, Lach B, Provias JP, Reddy K, Murty NK, Doble BW, Bhatia M, Hassell JA, Singh SK. Pyrvinium Targets CD133 in Human Glioblastoma Brain Tumor-Initiating Cells. Clinical Cancer Research. 2015 Dec 1;21(23):5324-37.
18. Nolte SM, Venugopal C, McFarlane N, Morozova O, Hallett RM, O'Farrell E, Manoranjan B, Murty NK, Klurfan P, Kachur E, Provias JP, Farrokhyar F, Hassell JA, Marra M, Singh SK. A cancer stem cell model for studying brain metastases from primary lung cancer. Journal of the National Cancer Institute. 2013 Apr 17;105(8):551-62.
19. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB. Identification of human brain tumour initiating cells. Nature. 2004 Nov 18;432(7015):396-401.
20. Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB. Identification of a cancer stem cell in human brain tumors. Cancer Res. 2003 Sep 15;63(18):5821-8.