The Tailor Lab studies the role of cancer predisposition genes on human neural stem cell differentiation and brain tumorigenesis with a view to developing novel techniques to stop brain cancer development.

Tailor Lab

The goal of the laboratory of Jignesh Tailor, BMBCH, PhD, is to understand how neural progenitors deviate away from their normal trajectory to generate brain and spinal cord tumors.

The Tailor Lab uses human neural stem cells as in vitro models of progenitors in the developing brain/spine and investigates the molecular and cellular effects of cancer predisposition genes on neural stem cell self-renewal and differentiation. Cancer predisposition gene mutations the Tailor Lab is actively studying include NF2 loss (Neurofibromatosis type 2) and PTCH loss (Gorlin syndrome).

Dr. Tailor and his team believe that understanding the early steps of brain tumorigenesis will lead to novel therapeutic strategies to prevent malignant tumors in patients with a brain cancer predisposition syndrome.

Active Research

NF2 loss in neuroepithelial stem (NES) cells
Patients with neurofibromatosis type 2 (NF2) are predisposed to ependymoma of the spinal cord and lower brainstem. In this project the Tailor Lab studies the effect of NF2 loss on differentiation of spinal and hindbrain neuroepithelial stem (NES) cells (Tailor J, Kittappa R, Leto K, et al., J Neurosci. 2013;33:30). Furthermore, the group explores the tumorigenic potential of radial glial cells derived from these cells and how NF2 loss affects the epigenetic landscape of these cells to confer tumorigenicity.

Identifying synthetic lethal targets in tumorigenic NES cells
Previously, the Tailor Lab showed that NES cells with MYCN or PTCH mutations generate human models of SHH-subtype medulloblastoma after orthotopic transplantation. Moreover, the methylomic profile of these tumors were closer to human medulloblastoma than the mouse counterpart (Huang & Tailor et al., Cell Stem Cell 2019;25:1-14). In this project the Tailor Lab studies the molecular machinery of MYCN and PTCH driven NES cells using large-scale genetic CRISPR screens to identify novel synthetic lethal genes in these brain cancer initiating cells.

Learn more about current Neurological Surgery Research

Research Funding

CURE Childhood Cancer Award 2022
IU School of Medicine Department of Neurosurgery Start-up Funds

Publications

A full list of publications by Jignesh Tailor, BMBCH, PhD, is available on PubMed.

Falk A, Koch P, Kesavan J, Takashima Y, Ladewig J, Alexander M, Wiskow O, Tailor J, Trotter M, Pollard S, Smith A, Brustle O. Capture of neuroepithelial-like stem cells from pluripotent stem cells provides a versatile system for in vitro production of human neurons. PLoS One 2012; 7(1): e29597

Tailor J, Kittappa R, Leto K, Gates M, Borel M, Paulsen O, Rossi F, Falk A, Smith A. Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency.Journal of Neuroscience July 24 2013; 33(30).

Čančer M, Hutter S, Holmberg KO, Rosén G, Sundström A, Tailor J, Bergström T, Garancher A, Essand M, Wechsler-Reya RJ, Falk A, Weishaupt H, Swartling FJ. Humanized Stem Cell Models of Pediatric Medulloblastoma Reveal an Oct4/mTOR Axis that Promotes Malignancy. Cell Stem Cell. 2019 Dec 5;25(6).

Huang M* & Tailor J*, Zhen Q, Gillmor AH, Miller ML, Weishaupt H, Chen J, Zheng T, Nash EK, McHenry LK, An Z, Ye F, Takashima Y, Clarke J, Ayetey H, Cavalli FMG, Luu B, Moriarity BS, Ilkhanizadeh S, Chavez L, Yu C, Kurian KM, Magnaldo T, Sevenet N, Koch P, Pollard SM, Dirks P, Snyder MP, Largaespada DA, Cho YJ, Phillips JJ, Swartling FJ, Morrissy AS, Kool M, Pfister SM, Taylor MD, Smith A, Weiss WA. Engineering Genetic Predisposition in Human Neuroepithelial Stem Cells Recapitulates Medulloblastoma Tumorigenesis. Cell Stem Cell 2019; 25: 1-14 (*joint 1st authorship)

Susanto E, Marin Navarro A, Zhou L, Sundström A, van Bree N, Stantic M, Moslem M, Tailor J, Rietdijk J, Zubillaga V, Hübner JM, Weishaupt H, Wolfsberger J, Alafuzoff I, Nordgren A, Magnaldo T, Siesjö P, Johnsen JI, Kool M, Tammimies K, Darabi A, Swartling FJ, Falk A, Wilhelm M. Modeling SHH-driven medulloblastoma with patient iPS cell-derived neural stem cells. Proc Natl Acad Sci U S A. 2020 Aug 18;117(33):20127-20138

Faculty Research Team

Jignesh Tailor, M.D., PhD

Assistant Professor of Neurological Surgery

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Additional Research Team Members

Noah Burket, Student

Scott Cooper, Lab Manager

Victoria Dershem, Technician