RESEARCH
The Gregory lab is involved in several lab-based and collaborative research projects that focus on identifying the genomic, genetic, and epigenetic underpinnings of complex neurological diseases. As early adopters of single cell and spatial expression profiling approaches, the Gregory lab and the Molecular Genomics Core are applying in situ sequencing technologies to identify signatures of neurological disease development and progression. These technologies profile RNA expression at single cell resolution and by applying panels of canonical markers of cell type/state we can elucidate cell-cell and cell-neighborhood interaction analyses to unravel the heterogeneity of tumor microenvironments and examine the spatial context of MS and Alzheimer’s disease.
Alzheimer’s Disease (AD)
The Gregory lab, together with collaborators Drs. Jerry Wang (Department of Pathology) and Dianne Cruz (Department of Psychiatry), is using spatial transcriptomics to characterize the RNA expression changes that occur with the progression of Alzheimer’s disease. These data are correlated with the microarchitecture of the brain and disease pathology to understand the molecular changes associated with the disease. We are also pairing these data with a long-read sequence platform to explore RNA splicing in a spatial context to determine the effects of AD pathology in isoform production.
Congratulations to Gregory lab PhD student, Odmaa Bayaraa, on receiving the 2026 Dean’s Award for Research Excellence (DARE) and the Duke Institute for Brain Science Wrenn Fellowship.
Odmaa is using transcriptomic approaches to decode Alzheimer’s disease and classify distinct brain cell types.
Atypical teratoid/rhabdoid tumor (ATRT)
Atypical teratoid/rhabdoid tumor (ATRT) is a rare, aggressive pediatric brain cancer with limited treatment options and high mortality, primarily affecting very young children. Although nearly all cases are driven by loss of the chromatin remodeling gene SMARCB1, ATRT exhibits substantial heterogeneity and is divided into three molecular subtypes, ATRT-TYR, ATRT-SHH, and ATRT-MYC, with distinct transcriptomic, epigenetic, and clinical features. The diversity of ATRT tumor biology currently limits the effectiveness of non-subtype-specific therapies, underscoring the need to better characterize the molecular and cellular mechanisms that define each subtype.
In collaboration with the Kids Research Institute (Perth, Australia) and the Children’s Brain Tumor Network (Children’s Hospital of Philadelphia), we use single-cell and spatial approaches to resolve the key biological features that drive ATRT heterogeneity in order to develop more targeted and effective subtype-specific therapies.
Blanco-Carmona, E. et al. A cycling, progenitor-like cell population at the base of atypical teratoid rhabdoid tumor subtype differentiation trajectories. Neuro-Oncol. 27, 3260–3275 (2025).
Ho, B. et al. Molecular subgrouping of atypical teratoid/rhabdoid tumors—a reinvestigation and current consensus. Neuro-Oncol.22, 613–624 (2020).
Johann, P.D. et al. Atypical teratoid/rhabdoid tumors are comprised of three epigenetic subgroups with distinct enhancer landscapes. Cancer Cell 29, 379–393 (2016).
Congratulations to Gregory lab PhD student, Max Bucklan, on being a winner of the Lasker Foundation's 2026 Video Contest!
Max uses leading-edge transcriptomic technologies to study the mechanisms of atypical teratoid/rhabdoid tumor.
Glioblastoma (GBM)
Glioblastoma (GBM) is the most common and aggressive primary brain cancer in adults with over 12,000 people diagnosed in the US each year1. Despite decades of research and the current standard of care treatment, median survival remains roughly 15 months2, and nearly all tumors return after initial treatment. What makes GBM so challenging is its remarkable heterogeneity3, 4, 5, 6: tumors differ dramatically not only between patients, but also within a single tumor and over the course of disease, which complicates efforts to design therapies that work durably for everyone.
With the help of multi-omics, our lab is broadly interested in understanding GBM through both a temporal lens (how tumors evolve over time and in response to treatment) and a spatial lens (how a tumor's location within the brain shapes its biology).
- Mackenzie Price, Christine Ann Pittman Ballard, Julia R Benedetti, Carol Kruchko, Jill S Barnholtz-Sloan, Quinn T Ostrom, CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2018–2022, Neuro-Oncology, Volume 27, Issue Supplement_4, October 2025, Pages iv1–iv66, https://doi.org/10.1093/neuonc/noaf194
- Stupp, Roger et al. “Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.” The New England journal of medicine vol. 352,10 (2005): 987-96. doi:10.1056/NEJMoa043330
- Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17:98–110
- Wang Q, Hu B, Hu X, Kim H, Squatrito M, Scarpace L, et al. Tumor evolution of glioma-intrinsic gene expression subtypes associates with immunological changes in the microenvironment. Cancer Cell. 2017;32:42–56.e6.
- Neftel, Cyril et al. “An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma.” Cell vol. 178,4 (2019): 835-849.e21. doi:10.1016/j.cell.2019.06.024
- Nomura, M., Spitzer, A., Johnson, K.C. et al. The multilayered transcriptional architecture of glioblastoma ecosystems. Nat Genet 57, 1155–1167 (2025). https://doi.org/10.1038/s41588-025-02167-5
Dr. Michael Fay, Dr. Paul Tooney, Dr. Cassandra Griffin: Mark Hughes Foundation (Newcastle, Australia)
Dr. Ang Beng-Ti and Dr. Carol Tang: Duke-NUS and National Neuroscience Institute (Singapore)
Dr. Sebastian Waszak: École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
Multiple Sclerosis (MS)
Multiple Sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) and the leading cause of neurological disability in young adults, affecting nearly one million people in the U.S. and over 2.8 million worldwide. Despite decades of research, the precise mechanisms that drive disease onset, progression, and variability between patients remain poorly understood. In particular, how diverse cell types in the central nervous system and immune system interact to shape lesion formation and repair is still unclear.
Emerging single-cell and multimodal approaches offer new opportunities to dissect these complex cellular and molecular dynamics at unprecedented resolution. Dr. Gregory is Principal Investigator of the MURDOCK_MS study which includes ~1,000 multiple sclerosis patients. This cohort has been used to identify multi-omic biomarkers to facilitate reclassification of the disease (Cote et al 2019, Multiple Sclerosis and Related Disorders), and to assess MS progression using ultra-high sensitivity protein assays in a cohort of primary progressive MS patients (Profiling serum neurofilament light chain and glial fibrillary acidic protein in primary progressive multiple sclerosis).
The Gregory lab is also exploring the efficacy of a novel hydroxyl-cholesterol (HC) treatment of remyelination in MS. Together with Drs. Eric Benner (Duke, Pediatrics), Mari Shinohara (Duke, Immunology), and Glenn Matsushima (UNC-CH, Microbiology and Immunology), this transformative study is trying to understand the cellular mechanisms in which HCs trigger the differentiation of neural progenitor cells into oligodendrocyte progenitor cells (OPCs) and/or OPCs into oligodendrocytes, the cell that is critical for triggering remyelination in MS. Early data provides exciting evidence of remyelination in the context of a demyelinating pre-clinical model of MS.
- Jakimovski D, Bittner S, Zivadinov R, Morrow SA, Benedict RH, Zipp F, Weinstock-Guttman B. Multiple sclerosis. Lancet. 2024 Jan 13;403(10422):183-202. doi: 10.1016/S0140-6736(23)01473-3. Epub 2023 Nov 7. PMID: 37949093.
- Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, Robertson N, La Rocca N, Uitdehaag B, van der Mei I, Wallin M, Helme A, Angood Napier C, Rijke N, Baneke P. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler. 2020 Dec;26(14):1816-1821. doi: 10.1177/1352458520970841. Epub 2020 Nov 11. PMID: 33174475; PMCID: PMC7720355.
- Dobson, R. and Giovannoni, G. (2019), Multiple sclerosis – a review. Eur J Neurol, 26: 27-40. https://doi.org/10.1111/ene.13819
SUMMARY
Dr. Gregory is a tenured Professor and Director of the Brain Tumor Omics Program (BTOP) in the Duke Department of Neurosurgery, the Vice Chair of Research in the Department of Neurology, and Director of the Molecular Genomics Core at the Duke Molecular Physiology Institute (DMPI). As a neurogenomicist, Dr. Gregory applies his experience gained from leading the sequencing of chromosome 1 for the Human Genome Project to elucidating the mechanisms underlying multi-factorial diseases using genetic, genomic, and epigenetic approaches. Dr. Gregory’s primary areas of research involve understanding the molecular processes associated with disease development and progression in brain tumors and Alzheimer’s disease, and novel drug induced white matter injury repair in multiple sclerosis. He is broadly regarded across Duke as a leader in the development of novel single cell and spatial molecular technologies towards understanding the pathogenic mechanisms of disease development. Dr. Gregory is also the Section Chair of Genomics and Epigenetics at the DMPI and Director of the Duke Center of Autoimmunity and MS in the Department of Neurology.
BSc, Royal Melbourne Institute of Technology, Melbourne, Australia
PhD, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
PUBLICATIONS
LINKS
News Articles
DMPI Faculty Appointments and Promotions
Simon Gregory among group of international members selected to 10x Genomics CTRN
Duke Single Cell Initiative Seminar Series
LAB NEWS
- Simon moderated a panel on gene-editing human embryos following the uproar following the claim of Dr. He Jiankui that he made the world's first genetically edited twins.
- Simon is quoted in an important new study regarding autism risks dependent on the age of the parents.
LAB MEMBERS
Originally from Massachusetts, Karen has been at Duke since 1999 and is the Assistant Director of the MGC. Outside of work she keeps busy with her twins and their demanding softball schedules.
Vaibhav (VJ) received his M.S. in Bioinformatics in India and has been in the bioinformatics field for 13+ years. Currently, he analyzes single cell, spatial, and bulk RNA seq data. VJ likes to read, loves travelling, and finds that Indian desserts always hit the sweet spot.
Stephanie is a Lab Analyst for the Molecular Genomics Core, and the lead for 10x Genomics Single Cell RNA sequencing services provided by the core. She loves spending time with her dogs and bird watching.
Emily is a Research Lab Analyst in the Molecular Genomics Core. By day, she is the lead for spatial services within the core and by night Emily plays Dungeons and Dragons, Magic the Gathering, and watches anime.
Kevin is a bioinformatician with a focus is on the analysis of glioma data derived from many different sequencing modalities. Originally from northeast Ohio, he is an auto racing fan and once had the opportunity to drive 190mph at Daytona!
Kevin is from China, with an M.D. and a Ph.D. in Neuroscience. He is a postdoc associate for @Duke_Neurology. Kevin's expertise & passion extend beyond academia to his love of sports, including soccer, tennis, badminton, skiing, surfing, & swimming.
Michael graduated from Penn State (B.S., Biomedical Engineering) & Carnegie Mellon (M.S., Computational Biology). He works on single cell & spatial transcriptomic data analysis and is interested in innovative analysis methods for spatial & highly multiplexed imaging-based data.
Ellora is a Research Analyst for the Molecular Genomics Core from Calgary, Canada. She work on the MGC’s 10x Genomics single cell projects, and run other assays as needed. Ellora loves spending time outside, doing yoga, hiking, and painting.
Odmaa is a grad student from Mongolia in @DukeUPGG program (B.S. in Biology, minor in CS from NYUAD). Odmaa is interested in studying neurodegenerative disease via spatial & single cell approaches. She is passionate about STEM outreach, and enjoys painting/drawing & rock climbing
Lauren is a graduate student in Duke University's Genetics and Genomics Program (UPGG). Originally from Jacksonville, Florida, she earned both her Bachelor’s and Master’s degrees from the University of North Florida. Her research is focused on studying the origins of glioblastoma using multi-omic approaches, aiming to deepen our understanding of this aggressive brain cancer. Outside of the lab, Lauren loves spending time in her garden, going to trivia nights, and cheering on the Jacksonville Jaguars (DTWD)!"
Emma is a grad student from South Carolina in the @DukeUPGG program and received her B.S. In Biochemistry from Clemson University. Emma is studying the lesion microenvironment in Multiple Sclerosis using single-cell and spatial transcriptomics. Outside of lab, she enjoys playing piano, drawing, and hiking.
Max is a graduate student in the Duke University Program in Genetics and Genomics and previously received his B.S. in Biology from Duke. Originally from Connecticut, Max is interested in using single cell and spatial transcriptomics to study the mechanisms of pediatric brain tumors. Max's side quests include being a cosplayer, an improv pianist, and an avid fan of bad science puns.