Sims Lab

Department of Systems Biology | Columbia University

Welcome

Welcome to the Sims Lab at Columbia University. Our group resides in the Department of Systems Biology and the Department of Biochemistry & Molecular Biophysics. We develop new tools for genomic analysis, focusing on applications in cancer and immunology. We are located on the 2nd floor of the Lasker Biomedical Research Building at Columbia University Irving Medical Center in New York City.

Microwell array for single-cell analysis

News

Research

Single Cell Genomics

Cells respond heterogeneously to chemical and genetic perturbations. The origin of this heterogeneity ranges from differences in cell morphology, microenvironment, and cell cycle stage to diversity in gene expression, epigenetic state, and genomic stability. Hence, single cell approaches are crucial to unbiased, system-wide analyses of biological samples. We are developing microfluidic devices, fluorescent probes, and sequencing tools for molecular profiling in individual cells. Examples include scalable methods for scRNA-seq and joint co-sequencing of mRNA and DNA, as well as technology for linking live cell imaging with single-cell sequencing. In addition, we have developed computational tools that leverage machine learning for analyzing single-cell genomic data, including probabilistic matrix factorization and automated cell type classification.

Cancer Systems Biology

Our cancer biology research takes advantage of the technologies described above and has historically focused on malignant brain tumors. Our earlier work involved molecular profiling of gliomas, resulting in multiple studies describing the cellular composition and molecular states that co-occur within individual tumors and appear across patients. More recently, we have combined acute slice culture of surgical specimens with single-cell genomics to analyze cell type-specific drug responses in gliomas. This approach preserves the native cellular composition and spatial features of solid tumors, allowing us to simultaneously assay the sensitivities of multiple transformed and microenvironmental cell types, including those that are poorly represented in conventional patient-derived models. Our cancer systems biology research benefits from active collaborations with many colleagues including Jeff Bruce, Peter Canoll, Andrea Califano, and Cory Abate-Shen, and we are gradually expanding to applications in other cancer types.

Systems Immunology

The immune system plays key roles in almost all aspects of human biology including development, tissue homeostasis, cancer, and response to pathogens and disease. Our lab has developed experimental and computational tools for characterizing the diversity and function of tissue resident immune populations in human organs. Major biological questions include: How are tissue-associated T cells functionally distinct from circulating T cells? What factors regulate the maturation of T cells in human tissues? How do tissue resident immune populations age? Why do different pathogens and vaccines induce dramatically different durations of protective immunity (memory)? We work on all of these questions in an exciting collaboration with the Farber lab at Columbia.

People

Principal Investigator

Peter Sims
Peter A. Sims
Herbert & Florence Irving Professor of Systems Biology
Scientific Director, Sulzberger Columbia Genome Center
Ph.D., Chemistry, Harvard University
Email

Research Staff

David Chen
M.S. Pharmaceutical Science, University at Buffalo
Siddhi Nargund
M.S. Biotechnology, Johns Hopkins
Emily Chao
M.S. Bioinformatics and Computational Biology, UT Dallas

Postdoctoral Fellows

Ana Paula Delgado
Ph.D. Genetics, Stony Brook University
Josué Curto Navarro
Ph.D. Biochemistry, Universitat Autònoma de Barcelona

Graduate Students

Alex George
M.D./Ph.D. Program
Abby Brand
Integrated Ph.D. Program
Shannon Weng
M.D./Ph.D. Program
Romella Sagatelian
Integrated Ph.D. Program, Systems Biology Track
Stephanie Andersen
M.D./Ph.D. Program
Madison Snyder
Pathobiology Ph.D. Program
Mike Matthews
M.D./Ph.D. Program

Former Group Members

Publications

* Equal Contribution  |  # Co-corresponding Author
Pre-prints
IDH-mutant inhibitors enhance the sensitivity of IDH1-mutant gliomas to cysteine-methionine deprivation and ferroptosis
Mela, A, Brand, A., Mahajan, A., Dovas, A., Humala, N., Kanangat, S., Kleinstein, A.C., Leskinen, S., Nguyen, T.T.T., Gao,Q., Upadhyayula, P.S., Guo, J., Gill, B., Siegelin, M.D., Sims, P.A., Stockwell, B.R., Bruce, J.N., Canoll, P.
bioRxiv (2026)
TMPO promotes cellular dissemination and metastasis in circulating tumor cells
Giacobbe, A., Obradovic, A.Z., Park, S., ... Sims, P.A.#, Abate-Shen, C.#
bioRxiv (2025)
A factor-based analysis of individual human microglia uncovers regulators of an Alzheimer-related transcriptional signature
Marshe, V.S., Tuddenham, J.F., ... Sims, P.A., De Jager, P.L.
bioRxiv (2025)
Decoding neuronal wiring by joint inference of cell identity and synaptic connectivity
Gupta, H.P., Azevedo, A.W., Chen, Y.D., Xing, K., Sims, P.A., Varol, E.#, Mann, R.S.#
bioRxiv (2025)
MAPK/ERK signaling in gliomas modulates interferon responses, T cell recruitment, microglia phenotype, and immune checkpoint blockade efficacy
Kim, K.S., Zhang, J., ... Sims, P.A., Rabadan, R., ... Sonabend, A.M.
bioRxiv (2024)
A pharmacological toolkit for human microglia identifies Topoisomerase I inhibitors as immunomodulators for Alzheimer's disease
Haage, V., Tuddenham, J.F., ... Sims, P.A., Menon, V., Picard, M., De Jager, P.L.
bioRxiv (2024)
Consensus scHPF identifies cell type-specific drug responses in glioma by integrating large-scale scRNA-seq
Levitin, H.M., Zhao, W., Bruce, J.N., Canoll, P., Sims, P.A.
bioRxiv (2023)
Single cell profiling of COVID-19 patients: an international data resource from multiple tissues
Ballestar, E., ... Sims, P.A., ... CZI Single-Cell COVID-19 Consortia
medRxiv (2020)
Single-cell based elucidation of molecularly distinct glioblastoma states and drug sensitivity
Ding, H.*, Burgenske, D.M.*, ... Canoll, P.#, Sims, P.A.#, Sarkaria, J.N.#, Califano, A.#
bioRxiv (2019)
2026
Distinct transcription factors control tissue adaptation and effector function in infant and adult memory T cells
Szabo, P.A., Levitin, H.M., Nargund, S., Connors, T.J., Chen, D., Jin, J., Thapa, P., Guyer, R., Caron, D.P., Gray, J.I., Matsumoto, R., Kubota, M., Brusko, M., Brusko, T.M., Farber, D.L.#, Sims, P.A.#
Nature Immunology, in press (2026)
Dissociable perfusion chip (DPC): perfusable microfluidic chip for single-cell screening of anti-cancer drugs in live glioblastoma explants
Kennedy, D.G.*, Zhao, W.*, Chern, T.L., Yang, M., Acosta, N., Arumugam, S., Upadhyayula, P., Furnari, J., Dovas, A., Bruce, J.N., Canoll, P., Sia, S.K.#, Sims, P.A.#
Lab on a Chip, 26, 2226 (2026)
Featured: "Chipping Away at Brian Cancer"
Visualization and quantification of rDNA instabilities in mammalian cells and mouse models
Zhu, X.*, Jiang, W.*, Wu, W., Lee, B.J., Menolfi, D., Tubbs, A., Cupo, O.M., Malkovskiy, E., Nester, M., Wang, X.S., Sims, P.A., Lin, C.V., Symington, L., Nussenzweig, A., McStay, B., Zha, S.
Nucleic Acids Research, 54, gkaf1523 (2026)
2025
Tissue signatures of human macrophages during homeostasis and activation
Caron, D.P., Specht, W.L., ... Sims, P.A.#, Farber, D.L.#
The Journal of Immunology, vkaf317 (2025)
Lung tissue–resident memory T cells optimize protection by IL-10 regulation of innate immunity
Yang, A.Y., Davis-Porada, J., ... Sims, P.A., ... Farber, D.L.
Journal of Experimental Medicine, 223, e20242307 (2025)
Multimodal profiling reveals tissue-directed signatures of human immune cells altered with age
Wells, S.B.*, Rainbow, D.B.*, ... Sims, P.A.#, Jones, J.L.#, Yosef, N.#
Nature Immunology, 26, 1612 (2025)
The spatial landscape of glial pathology and T cell response in Parkinson's disease substantia nigra
Ma, M., Paryani, F., ... Sims, P.A., Al-Dalahmah, O.
Nature Communications, 16, 7146 (2025)
Single-cell transcriptomic landscape of the neuroimmune compartment in amyotrophic lateral sclerosis brain and spinal cord
Tuddenham, J.F., Fujita, M., ... Sims, P.A., ... Olah, M.
Acta Neuropathologica, 150, 10 (2025)
ADTnorm: Robust integration of single-cell protein measurement across CITE-seq datasets
Zheng, Y.*, Caron, D.P.*, ... Sims, P.A., Gottardo, R.
Nature Communications, 16, 5852 (2025)
HDAC inhibitors engage MITF and the disease-associated microglia signature to enhance amyloid β uptake
Haage, V.*, Tuddenham, J.F.*, ... Sims, P.A., ... De Jager, P.L.
Brain, Behavior, and Immunity, 129, 279 (2025)
Phase II Study of Pexidartinib Plus Sirolimus in Unresectable Malignant Peripheral Nerve Sheath Tumors
Manji, G.A., ... Sims, P., ... Schwartz, G.K.
JCO Oncology Advances, 2, e2400083 (2025)
LIN28B-mediated PI3K/AKT pathway activation promotes metastasis in colorectal cancer models
Shin, A.E., ... Sims, P.A., Rustgi, A.K.
Journal of Clinical Investigation, 135, e186035 (2025)
Scalable co-sequencing of RNA and DNA from individual nuclei
Olsen, T.R., Talla, P., Sagatelian, R.K., Furnari, J., Bruce, J.N., Canoll, P., Zha, S., Sims, P.A.
Nature Methods, 22, 477 (2025)
Featured: "New Technique for Single-Cell Sequencing Enhances Drug Screening Research" | "Tools of the Trade" in Nature Reviews Genetics |"Year in Review 2025" in Nature Methods
Glioma-induced alterations in excitatory neurons are reversed by mTOR inhibition
Goldberg, A.R.*, Dovas, A.*, ... Sims, P.A., Peterka, D.S., Canoll, P.
Neuron, 113, 858 (2025)
Multimodal hierarchical classification of CITE-seq data delineates immune cell states across lineages and tissues
Caron, D.P., Specht, W.L., Chen, D., Wells, S.B., Szabo, P.A., Jensen, I.J., Farber, D.L., Sims, P.A.
Cell Reports Methods, 5, 100938 (2025)
Featured as the Cover Article in Cell Reports Methods
PRRX1 has functional roles in pancreatic acinar to ductal metaplasia and carcinogenesis
Nishiwaki, N.*, Sugiura, K.*, ... Sims, P.A., Chandwani, R., Rustgi, A.K.
Cellular and Molecular Gastroenterology and Hepatology, 19, 101442 (2025)
2024
Resistance to spindle inhibitors in glioblastoma depends on STAT3 and therapy induced senescence
Zarco, N., Dovas, A., ... Sims, P.A., ... Kenchappa, R.S.
iScience, 27, 111311 (2024)
Maintenance and functional regulation of immune memory to COVID-19 vaccines in tissues
Davis-Porada, J., George, A.B., Lam, N., Caron, D.P., ... Sims, P.A.#, Farber, D.L.#
Immunity, 57, 2895 (2024)
Featured: "Immune Memory to COVID-19 Vaccination is Stored Throughout the Body"
A cross-disease resource of living human microglia identifies disease-enriched subsets
Tuddenham, J.F., ... Sims, P.A., ... De Jager, P.L.
Nature Neuroscience, 27, 2521 (2024)
A cell state specific metabolic vulnerability to GPX4-dependent ferroptosis in glioblastoma
Banu M.A.*, Dovas, A.*, ... Sims, P.A.#, Canoll, P.D.#
EMBO Journal, 43, 4492 (2024)
FRA1 controls acinar cell plasticity during murine Kras(G12D)-induced pancreatic acinar to ductal metaplasia
Li, A.L., ... Sims, P.A.#, Rustgi, A.K.#
Developmental Cell, 59, 3025 (2024)
Human γδ T cells in diverse tissues exhibit site-specific maturation dynamics across the lifespan
Gray, J.I., ... Sims, P.A., Farber, D.L.
Science Immunology, 9, eadn3954 (2024)
Featured as the Cover Article in Science Immunology
Time-resolved fate mapping identifies the intestinal upper crypt zone as an origin of Lgr5+ crypt base columnar cells
Capdevila, C., ... Sims, P.A., Yan, K.S.
Cell, 187, 3039 (2024)
Multiplexed single-cell lineage tracing of mitotic kinesin inhibitor resistance in glioblastoma
Cheng, Y.L., Banu, M.A., Zhao, W., Rosenfeld, S.S., Canoll, P., Sims, P.A.
Cell Reports, 43, 114139 (2024)
RZiMM-scRNA: A regularized zero-inflated mixture model framework for single-cell RNA-seq data
Mi, X., Bekerman, W., Rustgi, A.K., Sims, P.A., Canoll, P.D., Hu, J.
Annals of Applied Statistics, 18, 1 (2024)
2023
Single-cell analysis of 5-aminolevulinic acid intraoperative labeling specificity for glioblastoma
Liu, Z., Mela, A., Argenziano, M.G., ... Sims, P.A.
Journal of Neurosurgery, 140, 968 (2023)
Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity
Matsumoto, R.*, Gray, J.*, ... Sims, P.A., Hertz, T., Farber, D.L.
Nature Immunology, 24, 1370 (2023)
Site-specific development and progressive maturation of human tissue-resident memory T cells over infancy and childhood
Connors, T.J., Matsumoto, R., ... Sims, P.A., Farber, D.L.
Immunity, 56, 1894 (2023)
LIN28B promotes cell invasion and colorectal cancer metastasis via CLDN1 and NOTCH3
Sugiura, K., ... Sims, P.A., Lengner, C.J., Rustgi, A.K.
JCI Insight, e167310 (2023)
Re-convolving the compositional landscape of primary and recurrent glioblastoma reveals prognostic and targetable tissue states
Al-Dalahmah, O.#, ... Sims, P.A., Menon, V.#, Canoll, P.#
Nature Communications, 14, 2586 (2023)
Conserved and cell type-specific transcriptional responses to IFN-γ in the ventral midbrain
Hobson, B.D., ... Sims, P.A.#, Sulzer, D.#
Brain, Behavior, and Immunity, 111, 277 (2023)
Featured as the Cover Article in Brain, Behavior, and Immunity
A transcriptome-based precision oncology platform for patient-therapy alignment
Mundi, P.S., ... Sims, P.A., Alvarez, M.J., Kung, A.L., Califano, A.
Cancer Discovery, CD-22-1020 (2023)
Tissue adaptation and clonal segregation of human memory T cells in barrier sites
Poon, M.M.L.*, Caron, D.P.*, ... Sims, P.A., Farber, D.L.
Nature Immunology, 24, 309 (2023)

Contact

Lab Address:
Columbia University Medical Center
Lasker Biomedical Research Building
3960 Broadway, 2nd Floor, Room 203AC
New York, NY 10032

Phone: (212) 305-2687
Email