Neuro-Oncology Research
Below are labs and faculty who are developing new therapeutic agents and gene therapy to treat malignant and benign tumors through clinical and laboratory research.
We are actively translating the discoveries in our basic science laboratories into clinical trial opportunities for our patients. For more information, visit the Malnati Brain Tumor Institute’s Clinical Trials page.
Labs
Cheng LabDr. Cheng’s lab investigates cancer stem cell biology, cellular signaling and therapy responses in human brain tumors, particularly glioblastoma (GBM).
Dr. Cheng’s lab investigates cancer stem cell biology, cellular signaling and therapy responses in human brain tumors, particularly glioblastoma (GBM).
Research Description
Our lab broadly studies cancer stem cell biology, cellular signaling, RNA biology, and therapy responses in human brain tumors, in particular, glioblastoma (GBM). We have a range of different projects currently underway in glioma cell lines, gliomas stem-like cells (GSCs), patient-derived xenograft (PDX) GBM model, human iPSC-derived glioma organoid model, orthotopic glioma xenograft model in mice, and clinical glioma tumor specimens. Our current research focuses on novel mechanisms/cellular signaling of GSC biology, tumorigenesis, progression, and therapy responses of GSCs and GBMs.
Roles of RNA alternative splicing and RNA-binding proteins in glioma
RNA alternative splicing (AS), an evolutionarily conserved co-transcriptional process, is an important and influential determinant of transcriptome and proteome landscapes in normal and disease states such as cancer. AS is regulated by a group of RNA binding proteins (RBPs) that bind to the cis-acting elements in proximity to a splice site thus affecting spliceosome assembly. In cancers, altered expression of or mutations in RBPs result in dysregulated AS that impacts cancer biologic properties. We have established AS/RBP networks that are dysregulated in both adult and pediatric gliomas through bioinformatic analysis of both public and our own datasets of clinical glioma tumors. We are investigating the biological significance of AS/RBPs dysregulation in glioma progression and therapy response by using human iPSC-derived glioma organoid model and GSC brain xenograft models in animals. In addition, we are exploring novel therapeutic approaches of targeting glioma-associated AS/RBP networks to treat GBMs.
Roles of Non-coding RNAs in glioma
Non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), act as transcription repressors or inducers of gene expression or functional modulators in all multicellular organisms. Dysregulated ncRNAs plays critical roles in cancer initiation, progression and responses to therapy. We study the mechanisms by which deregulated expression of lncRNAs or circRNAs influence GBM malignant phenotypes through interactions with signaling pathways. We study the molecular consequences and explore clinical applications of modulating ncRNAs and related oncogenic signaling pathways in GBM. We are establishing profiles of ncRNAs in clinical gliomas and patient-derived GSCs, and study mechanisms and biological influences of these ncRNAs in regulating GSC biology and GBM phenotypes.
Aberrant DNA and RNA structures in therapy-resistant GBM
Standard of care treatment for GBM includes the DNA damaging agent temozolomide (TMZ), which has a known mechanism of action to target and mutate guanine bases. With this knowledge in hand, we sought to determine the effects of guanine (G) mutations in DNA and RNA secondary structure. G’s are important for creating structures like g-quadruplexes in both DNA and RNA which can affect changes in translation or be used as docking sites for DNA repair and RNA binding proteins. Using whole genome sequencing data along with isogenic drug sensitive and resistant lines, we are investigating the role of G mutations in DNA and RNA secondary structure to determine potential therapeutic avenues with the help of a chemical biologist to create novel drugs to target these TMZ-induced aberrant pathways.
Targeting autophagy to treat glioma
Autophagy is an evolutionarily conserved process that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism, thus serving as a protective mechanism against stressors and diverse pathologies including cancer. We study mechanisms by which phosphorylation, acetylation and ubiquitination of autophagy-related proteins regulate GSC and GBM phenotypes and autophagic response, which, in turn contributes to tumor cell survival, growth and resistance to therapy. We investigate whether disruption of these post-translational processes in autophagy-related proteins inhibits autophagy and enhances the efficacy of combination therapies in GBMs. In collaboration with a medicinal chemist, we are characterizing a next generation of novel autophagy inhibitors that specifically target a key autophagy regulator that we recently reported.
Multi-omics and GBM non-responsiveness to immunotherapies
GBM is categorized as a “cold” tumor that does not respond to current immunotherapies using various immune-checkpoint blockers. Although extensive efforts have been made to sensitize GBM to immunotherapies, the mechanistic studies to determine alternative therapies from understanding the underlying signaling and clinical trial results are still disappointing. We are interested in utilizing the information of multi-omics of clinical gliomas, in particular, proteomics profiling in relation to genomic and epigenomic profiling, to identify potential protein targets that could be the major modulators through post-translational modifications in these “cold” GBM tumors. We will also consider the involvement of tumor microenvironment and immune cells in these conditions. These studies are a brand-new direction that are high-risk and high-reward to turn “cold” GBM tumors to immunotherapy responsive tumors.
For more information, please see Dr. Cheng's faculty profile and lab website.
Publications
View Dr. Cheng's complete list of publications in PubMed.
Contact Us
Shi-Yuan Cheng, PhD at 312-503-5314
Visit us on campus in the Lurie Building, Room 6-119, 303 E Superior Street, Chicago, Illinois 60611.
Alexander Stegh LabDr. Stegh’s lab aims to define and target the oncogenome of glioblastoma.
Dr. Stegh’s lab aims to define and target the oncogenome of glioblastoma.
Research Description
Our research program is aimed at understanding the genetic program that underlies the pathogenesis of Glioblastoma multiforme (GBM), the most prevalent and malignant form of brain cancer. Applying a combination of cell/molecular biology, oncogenomic and mouse engineering approaches, we are dedicated to systematically characterize novel gliomagenic oncogenes and tumor suppressors. We will functionally delineate and validate these pathways using cell culture and animal models and develop novel nanotechnological approaches to target these aberrations in established tumors.
For more information see the faculty profile of Alexander H. Stegh MD, PhD.
Recent Publications
View Dr. Stegh's full list of publications at PubMed.
Contact
Email Alexander Stegh, MD, PhD
Phone: 312-503-2879
Research Faculty
Cheng, Shi-Yuan
Professor, Neurology (Neuro-oncology)
Dixit, Karan S
Assistant Professor, Neurology (Neuro-oncology), Neurology (Hospital Neurology)
Fushimi, Kazuo
Research Assistant Professor, Neurology (Neuro-oncology)
Hu, Bo
Research Associate Professor, Neurology (Neuro-oncology)
Kumthekar, Priya U
Associate Professor, Neurology (Neuro-oncology), Medicine (Hematology and Oncology)
Lukas, Rimas V
Associate Professor, Neurology (Neuro-oncology), Neurology (Hospital Neurology)
Raizer, Jeffrey J
Adjunct Professor, Neurology (Neuro-oncology)
Stegh, Alexander H
Adjunct Professor, Neurology (Neuro-oncology)
Stupp, Roger
Professor, Neurological Surgery, Medicine (Hematology and Oncology), Neurology (Neuro-oncology)