Research

Our laboratory investigates the molecular mechanisms that regulate normal development and how their dysregulation contributes to disease, with a central focus on the neurogenesis repressor REST. Our research has uncovered links between REST and stemness, lineage plasticity, cancer and neuropathic pain.

Stemness in Normal Stem Cells and Brain Tumors
We and others have demonstrated that the transcriptional repressor REST is required to maintain stemness in normal neural stem cells during development, after which its expression is drastically reduced. Our laboratory subsequently discovered that aberrant re-expression of REST functions as an oncogenic driver in the pediatric brain tumor medulloblastoma by sustaining aberrant stem-like states. This work provided early mechanistic evidence that dysregulated stemness contributes to brain tumor pathogenesis and informed subsequent studies examining stem-like programs in medulloblastoma and the adult brain tumor glioblastoma.

Lineage Plasticity
Prior to the advent of induced pluripotent stem cell technologies, our laboratory demonstrated that muscle progenitor cells can be reprogrammed into functional neurons through a transcriptional shift induced by an engineered transcription factor that activates REST target genes. This work provided early evidence that cell fate can be redirected through targeted transcriptional regulation, highlighting the role of lineage plasticity in development and disease.

REST-Mediated Regulation of Stemness in Embryonic Stem Cells
Our laboratory has shown that REST contributes to the maintenance of embryonic stem cell pluripotency by regulating core pluripotency factors through a microRNA-dependent mechanism. Subsequent studies revealed that REST’s effects on pluripotency are context-dependent, varying with cell type and culture conditions. These findings highlight the complexity of transcriptional regulatory networks that govern stem cell identity.

REST–microRNA–Neurotransmitter Regulation in Glioblastoma
Our laboratory has shown that REST influences glioblastoma stem-like cell (GSC) properties through microRNA-mediated regulation of stemness-associated pathways. We further demonstrated that REST regulates GSC invasion and tumorigenicity through distinct microRNA- and neurotransmitter-linked mechanisms, contributing to a better understanding of GSC heterogeneity.

REST Regulation of Neuropathic Pain
Others have shown that aberrant REST overexpression in dorsal root ganglion neurons contributes to nerve injury-induced neuropathic pain. Using conditional REST gain- and loss-of-function models, our laboratory has linked REST to transcriptional programs that modulate pain signaling in peripheral sensory neurons.
 

We are deeply committed to mentoring scientists at all career stages, and our lab has trained more than 70 undergraduates, Ph.D. students, postdoctoral fellows and clinical fellows, many of whom now hold independent academic positions worldwide. Dr. Majumder has served on the UT MD Anderson Faculty Academic Mentoring Council and remains actively engaged in mentoring across institutional and international networks. Our trainees are first authors on all our publications. We also actively disseminate research resources developed in the Majumder Laboratory — including genetically engineered mouse models, cell lines and key reagents — to promote rigor, reproducibility and broad impact.