Simon Gregory, PhD

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)

Alzheimer's Disease Schematic Figure

Alzheimer's disease is a progressive brain disorder and the leading cause of dementia, affecting memory, thinking, and independence. An estimated 7.4 million Americans age 65 and older live with Alzheimer's today — about 1 in 9 older adults.

The Gregory lab studies the molecular changes underlying Alzheimer's disease, together with collaborators Drs/Profs. Jerry Wang (Department of Pathology), Dianne Cruz (Department of Psychiatry), Kai Wang (Children's Hospital of Philadelphia, University of Pennsylvania), and Jinmiao Chen (Duke-NUS). One major focus of this work uses spatial transcriptomics — including 10x Genomics Visium and Xenium platforms — to map how gene expression changes as Alzheimer's progresses, directly within the brain's own microarchitecture. By correlating these molecular changes with tissue structure and disease pathology, we aim to understand how and where Alzheimer's disrupts the brain at a cellular level.

We're also pairing this spatial data with PacBio long-read sequencing to study RNA splicing in its native spatial context. A particular focus of our work is understanding how Alzheimer's pathology affects isoform expression in specific cell types — revealing not just which genes are affected, but how individual cell types alter the way they read and process their genetic instructions as disease progresses.

  1. Luquez, T., Algoo, J., Chiu, R. et al. Cell-type signatures of Alzheimer’s disease shared across population groups. Nature 657, 191–201 (2026). https://doi.org/10.1038/s41586-026-10793-0
  2. Heberle BA, Brandon JA, Page ML, Nations KA, Dikobe KI, White BJ, Gordon LA, Fox GA, Wadsworth ME, Doyle PH, Williams BA, Fox EJ, Shantaraman A, Ryten M, Goodwin S, Ghiban E, Wappel R, Mavruk-Eskipehlivan S, Miller JB, Seyfried NT, Nelson PT, Fryer JD, Ebbert MTW. Using deep long-read RNAseq in Alzheimer's disease brain to assess medical relevance of RNA isoform diversity. bioRxiv [Preprint]. 2023 Dec 11:2023.08.06.552162. doi: 10.1101/2023.08.06.552162. Update in: Nat Biotechnol. 2025 Apr;43(4):635-646. doi: 10.1038/s41587-024-02245-9. PMID: 37609156; PMCID: PMC10441303.
  3. Gabitto, M.I., Travaglini, K.J., Rachleff, V.M. et al. Integrated multimodal cell atlas of Alzheimer’s disease. Nat Neurosci 27, 2366–2383 (2024). https://doi.org/10.1038/s41593-024-01774-5 

Check out Odmaa's recent AD publication in Springer Nature: Multi-region spatial transcriptomics reveals region specific differences in response to amyloid beta (Aβ) plaque induced changes in Alzheimer’s disease (AD)
 

Read our paper
Headshot Portrait of Odmaa Bayaraa

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)

Brain Tumor Illustration

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.

Max Bucklan holding a Lego Set in Shape of Brain

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)

In Situ Transcriptomics (Xenium) Image of Glioblastoma

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).

  1. 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
  2. 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
  3. 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
  4. 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.
  5. 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
  6. 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)

In Situ Transcriptomics (Xenium) Image of Multiple Sclerosis Lesion

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).

SGregory Remyellination Research

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.

  1. 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.
  2. 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.
  3. Dobson, R. and Giovannoni, G. (2019), Multiple sclerosis – a review. Eur J Neurol, 26: 27-40. https://doi.org/10.1111/ene.13819

  1. Sawcer S, Ban M, Maranian M, Yeo TW, Compston A, Kirby A, Daly MJ, De Jager PL, Walsh E, Lander ES, Rioux JD, Hafler DA, Ivinson A, Rimmler J, Gregory SG, Schmidt S, Pericak-Vance MA, Akesson E, Hillert J, Datta P, Oturai A, Ryder LP, Harbo HF, Spurkland A, Myhr KM, Laaksonen M, Booth D, Heard R, Stewart G, Lincoln R, Barcellos LF, Hauser SL, Oksenberg JR, Kenealy SJ, Haines JL; International Multiple Sclerosis Genetics Consortium.  A high-density screen for linkage in multiple sclerosis.  Am J Hum Genet; 77(3):454-67.  Sep 2005. Epub 2005 Jul 29. PMID: 16080120. PMCID: PMC1226210
  2. Kenealy SJ, Herrel LA, Bradford Y, Schnetz-Boutaud N, Oksenberg JR, Hauser SL, Barcellos LF, Schmidt S, Gregory SG, Pericak-Vance MA, Haines JL.  Examination of seven candidate regions for multiple sclerosis: strong evidence of linkage to chromosome 1q44.  Genes Immun. 2006 Jan;7(1):73-6. PMID: 16341055
  3. Brassat D, Motsinger AA, Caillier SJ, Erlich HA, Walker K, Steiner LL, Cree BA, Barcellos LF, Pericak-Vance MA, Schmidt S, Gregory S, Hauser SL, Haines JL, Oksenberg JR, Ritchie MD.  Multifactor dimensionality reduction reveals gene-gene interactions associated with multiple sclerosis susceptibility in African Americans. Genes Immun. 2006 Apr 20; Jun;7(4):310-5. PMID: 16625214. PMCID: PMC4339061
  4. Schmidt S, Pericak-Vance MA, Sawcer S, Barcellos LF, Hart J, Sims J, Prokop AM, van der Walt J, DeLoa C, Lincoln RR, Oksenberg JR, Compston A, Hauser SL, Haines JL, Gregory SG. Allelic Association of Sequence Variants in the Herpes Virus Entry Mediator-B Gene (PVRL2) with the Severity of Multiple Sclerosis. 2006 Genes Immun. Jul;7(5):384-92. PMID: 16738668
  5. Motsinger AA, Brassat D, Caillier SJ, Erlich HA, Walker K, Steiner LL, Barcellos LF, Pericak-Vance MA, Schmidt S, Gregory S, Hauser SL, Haines JL, Oksenberg JR, and  Ritchie MD. Complex gene-gene interactions in multiple sclerosis: a multifactorial approach reveals associations with inflammatory genes.  Neurogenetics.  2007 Jan;8(1):11-20. Epub 2006 Sep 22. PMID: 17024427
  6. Yeo TW, De Jager PL, Gregory SG, Barcellos LF, Walton A, Goris A, Fenoglio C, Ban M, Taylor CJ, Goodman RS, Walsh E, Wolfish CS, Horton R, Traherne J, Beck S, Trowsdale J, Caillier SJ, Ivinson AJ, Green T, Pobywajlo S, Lander ES, Pericak-Vance MA, Haines JL, Daly MJ, Oksenberg JR, Hauser SL, Compston A, Hafler DA, Rioux JD, Sawcer S.  A second major histocompatibility complex susceptibility locus for multiple sclerosis.  Ann Neurol. 2007 Mar;61(3):228-36. PMID: 17252545. PMCID: PMC2737610.
  7. Gregory SG, Schmidt S, Seth P, Oksenberg JR, Hart J, Prokop A, Caillier SJ, Ban M, Goris A, Barcellos LF, Lincoln R, McCauley JL, Sawcer SJ, Alasdair D, Compston S, Dubois B, Hauser SL, Garcia-Blanco MA, Pericak-Vance MA, Haines JL, the Multiple Sclerosis Genetics Group. Interleukin 7 receptor a chain (IL7R) shows allelic and functional association with multiple sclerosis. Nat Genet. 2007 Sep;39(9):1083-91. PMID: 1766081
  8. International Multiple Sclerosis Genetics Consortium1, Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL, de Bakker PI, Gabriel SB, Mirel DB, Ivinson AJ, Pericak-Vance MA, Gregory SG, Rioux JD, McCauley JL, Haines JL, Barcellos LF, Cree B, Oksenberg JR, Hauser SL.  Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study. N Engl J Med. 2007. Aug 30;357(9):851-62. Epub 2007 Jul 29. PMID: 17660530
  9. Maier LM, Lowe CE, Cooper J, Downes K, Anderson DE, Severson C, Clark PM, Healy B, Walker N, Aubin C, Oksenberg JR, Hauser SL, Compston A, Sawcer S; International Multiple Sclerosis Genetics Consortium, De Jager PL, Wicker LS, Todd JA, Hafler DA. IL2RA genetic heterogeneity in multiple sclerosis and type 1 diabetes susceptibility and soluble interleukin-2 receptor production. PLoS Genet. 2009 Jan;5(1):e1000322. Epub 2009 Jan 2. PMID: 19119414. PMCID: PMC2602853
  10. McCauley JL, Zuvich RL, Bradford Y, Kenealy SJ, Schnetz-Boutaud N, Gregory SG, Hauser SL, Oksenberg JR, Mortlock DP, Pericak-Vance MA, Haines JL.  Follow-up examination of linkage and association to chromosome 1q43 in multiple sclerosis. Genes Immun. 2009 Oct;10(7):624-30. Epub 2009 Jul 23. PMID: 19626040. PMCID: PMC2765552
  11. Cree BA, Rioux JD, McCauley JL, Gourraud PA, Goyette P, McElroy J, De Jager P, Santaniello A, Vyse TJ, Gregersen PK, Mirel D, Hafler DA, Haines JL, Pericak-Vance MA, Compston A, Sawcer SJ, Oksenberg JR, Hauser SL; IMAGEN; IMSGC. A major histocompatibility Class I locus contributes to multiple sclerosis susceptibility independently from HLA-DRB1*15:01. PLoS One. 2010 Jun 25;5(6):e11296. PMID: 20593013. PMCID: PMC2892470
  12. Evsyukova I, Somarelli JA, Gregory SG, Garcia-Blanco MA. Alternative splicing in multiple sclerosis and other autoimmune diseases. RNA Biol. 2010 Jul-Aug;7(4):462-73. Epub 2010 Jul 1. PMID: 20639696. PMID: 20593013. PMCID: PMC3070910
  13. Galarza-Muñoz G, Briggs FB, Evsyukova I, Schott-Lerner G, Kennedy EM, Nyanhete T, Wang L, Bergamaschi L, Widen SG, Tomaras GD, Ko DC, Bradrick SS, Barcellos LF, Gregory SG*, Garcia-Blanco MA*. Human Epistatic Interaction Controls IL7R Splicing and Increases Multiple Sclerosis Risk. Cell. 2017 Mar 23;169(1):72-84.e13. doi: 10.1016/j.cell.2017.03.007. PMID: 28340352. PMCID: PMC5456452
  14. Andersen SL, Briggs FBS, Winnike JH, Natanzon Y, Maichle S, Knagge KJ, Newby LK, Gregory SG. Metabolome-based signature of disease pathology in MS. Multiple Sclerosis and Related Disorders. Mult Scler Relat Dis. 2019 Jun. doi: 10.1015 Epub 2019 Mar 9. PMID: 30877925
  15. Giarraputo J, Giamberardino S, Arvai S, Maichle S, Eckstein C, Newby LK, Gregory SG. Profiling  serum  neurofilament light chain and glial fibrillary acidic protein in primary progressive multiple sclerosis. J Neuroimmunol. 2021 May 15;354:577541. doi: 10.1016/j.jneuroim.2021.577541. Epub 2021 Mar 5. PMID: 33725477.
  16. SoRelle ED, Haukenfrers E, Horn GQ, Jain V, Giarraputo J, Abramson K, Hocke E, Cooney LA, Harris KM, Zamvil SS, Gregory SG, Luftig MA. Early multiple sclerosis activity associated with TBX21+CD21loCXCR3+ B cell expansion resembling EBV-induced phenotypes. JCI Insight 10, no. 12 (June 23, 2025).
  17. Briggs FBS, Mahmoudi F, Fereida-Esfahani M, Sagen J, Nelson F, Oksenberg J, Gregory S, Tobin WO. Serum metabolomic signatures of relapse recovery in early multiple sclerosis. Mult Scler Relat Disord. 2026 Feb 17;108:107082. doi: 10.1016/j.msard.2026.107082. Online ahead of print. PMID: 41724140
  18. Briggs FB, Litwiler J, Montini F, Fereidan Esfahani M, Sagen J, McCauley JL, Nelson F, Gregory S, Brambilla R, Trapl ES, Cooke Bailey JN, Schwerdtfeger LA, Cox L, Weiner H, Tobin WO. Tobacco smoking disrupts bile acid and tryptophan metabolism in multiple sclerosis. Mult Scler. 2026 Jul 1:13524585261454207. doi: 10.1177/13524585261454207. Online ahead of print. PMID: 42383698

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

Publications List

LINKS

News Articles

DMPI Faculty Appointments and Promotions

Simon Gregory among group of international members selected to 10x Genomics CTRN

An EPA Oscar

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

Gregory Lab Group Photo on Carmichael Staircase

 

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.

Sicheng Jing is a Master of Biostatistics student at Duke University. She received her B.S. in Bioinformatics from UC San Diego and is interested in computational genomics, transcript isoforms, and protein structure analysis, with a particular interest in neurological diseases. Outside of research, Sicheng enjoys cooking, trying new recipes, and watching anime.

Gregory Lab Photo Album