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Moffitt Lab Research
PCMM Research

Research Overview

The Moffitt laboratory is passionate about creating the next generation of image-based approaches to single-cell 'omics and leveraging these approaches to ask questions at the interface between commensal microbial communities and their host.
Researcher

Research Background

Dr. Moffitt received his PhD in Physics from the University of California Berkeley where he built methods to follow the Angstrom-scale movements of individual enzymes in real time. He trained as a postdoctoral fellow at Harvard University where he co-developed a leading method for massively multiplexed single-molecule RNA imaging known as MERFISH.

Selected Publications

  1. Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling. https://www.biorxiv.org/content/10.1101/2023.05.08.539701v1
  2. Spatial transcriptomics reveals the distinct organization of mouse prefrontal cortex and neuronal subtypes regulating chronic pain. https://www.nature.com/articles/s41593-023-01455-9
  3. Spatial and temporal profiling of the complement system uncovered novel functions of the alternative complement pathway in brain development. https://www.biorxiv.org/content/10.1101/2023.11.22.568325v1
  4. 4. The emerging landscape of spatial profiling technologies. https://www.nature.com/articles/s41576-022-00515-3

Publications

  1. Highly multiplexed spatial transcriptomics in bacteria. Science. 2025 Jan 24; 387(6732):eadr0932. View Abstract
  2. Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution. Nat Commun. 2025 Jan 02; 16(1):319. View Abstract
  3. Identifying spatially variable genes by projecting to morphologically relevant curves. bioRxiv. 2024 Nov 21. View Abstract
  4. Highly Multiplexed Spatial Transcriptomics in Bacteria. bioRxiv. 2024 Jun 27. View Abstract
  5. Accurate single-molecule spot detection for image-based spatial transcriptomics with weakly supervised deep learning. Cell Syst. 2024 May 15; 15(5):475-482.e6. View Abstract
  6. Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling. Cell. 2024 04 11; 187(8):2010-2028.e30. View Abstract
  7. Accurate single-molecule spot detection for image-based spatial transcriptomics with weakly supervised deep learning. bioRxiv. 2024 Feb 05. View Abstract
  8. Gut complement induced by the microbiota combats pathogens and spares commensals. Cell. 2024 Feb 15; 187(4):897-913.e18. View Abstract
  9. Corrigendum to 'Spatial enrichment of the type 1 interferon signature in the brain of a neuropsychiatric lupus murine model [Brain, Behav. Immun. (2023) 114, 511-522]. Brain Behav Immun. 2024 Feb; 116:419. View Abstract
  10. Spatial transcriptomics reveals the distinct organization of mouse prefrontal cortex and neuronal subtypes regulating chronic pain. Nat Neurosci. 2023 Nov; 26(11):1880-1893. View Abstract
  11. Author Correction: Spatial organization of the mouse retina at single cell resolution by MERFISH. Nat Commun. 2023 Sep 28; 14(1):6057. View Abstract
  12. [WITHDRAWN] Spatial enrichment of the type 1 interferon signature in the brain of a neuropsychiatric lupus murine model. bioRxiv. 2023 Sep 06. View Abstract
  13. Spatial organization of the mouse retina at single cell resolution by MERFISH. Nat Commun. 2023 08 15; 14(1):4929. View Abstract
  14. Spatial enrichment of the type 1 interferon signature in the brain of a neuropsychiatric lupus murine model. Brain Behav Immun. 2023 11; 114:511-522. View Abstract
  15. Charting the cellular biogeography in colitis reveals fibroblast trajectories and coordinated spatial remodeling. bioRxiv. 2023 May 09. View Abstract
  16. Microbiome induced complement synthesized in the gut protects against enteric infections. bioRxiv. 2023 Feb 03. View Abstract
  17. The emerging landscape of spatial profiling technologies. Nat Rev Genet. 2022 12; 23(12):741-759. View Abstract
  18. Cell segmentation in imaging-based spatial transcriptomics. Nat Biotechnol. 2022 03; 40(3):345-354. View Abstract
  19. National Cancer Institute Think-Tank Meeting Report on Proteomic Cartography and Biomarkers at the Single-Cell Level: Interrogation of Premalignant Lesions. J Proteome Res. 2020 05 01; 19(5):1900-1912. View Abstract
  20. MAFG-driven astrocytes promote CNS inflammation. Nature. 2020 02; 578(7796):593-599. View Abstract
  21. Multiplexed detection of RNA using MERFISH and branched DNA amplification. Sci Rep. 2019 05 22; 9(1):7721. View Abstract
  22. Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region. Science. 2018 11 16; 362(6416). View Abstract
  23. Author Correction: Multiplexed imaging of high-density libraries of RNAs with MERFISH and expansion microscopy. Sci Rep. 2018 Apr 19; 8(1):6487. View Abstract
  24. Multiplexed imaging of high-density libraries of RNAs with MERFISH and expansion microscopy. Sci Rep. 2018 03 19; 8(1):4847. View Abstract
  25. High-throughput, image-based screening of pooled genetic-variant libraries. Nat Methods. 2017 Dec; 14(12):1159-1162. View Abstract
  26. High-performance multiplexed fluorescence in situ hybridization in culture and tissue with matrix imprinting and clearing. Proc Natl Acad Sci U S A. 2016 12 13; 113(50):14456-14461. View Abstract
  27. High-throughput single-cell gene-expression profiling with multiplexed error-robust fluorescence in situ hybridization. Proc Natl Acad Sci U S A. 2016 09 27; 113(39):11046-51. View Abstract
  28. Spatial organization of chromatin domains and compartments in single chromosomes. Science. 2016 Aug 05; 353(6299):598-602. View Abstract
  29. Spatial organization shapes the turnover of a bacterial transcriptome. Elife. 2016 05 20; 5. View Abstract
  30. RNA Imaging with Multiplexed Error-Robust Fluorescence In Situ Hybridization (MERFISH). Methods Enzymol. 2016; 572:1-49. View Abstract
  31. Super-resolution imaging reveals distinct chromatin folding for different epigenetic states. Nature. 2016 Jan 21; 529(7586):418-22. View Abstract
  32. RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single cells. Science. 2015 Apr 24; 348(6233):aaa6090. View Abstract
  33. Characterization and development of photoactivatable fluorescent proteins for single-molecule-based superresolution imaging. Proc Natl Acad Sci U S A. 2014 Jun 10; 111(23):8452-7. View Abstract
  34. Simultaneous dual-color 3D STED microscopy. Opt Express. 2014 Mar 24; 22(6):7028-39. View Abstract
  35. Fast compressed sensing analysis for super-resolution imaging using L1-homotopy. Opt Express. 2013 Nov 18; 21(23):28583-96. View Abstract
  36. Extracting signal from noise: kinetic mechanisms from a Michaelis-Menten-like expression for enzymatic fluctuations. FEBS J. 2014 Jan; 281(2):498-517. View Abstract
  37. Statistical analysis of molecular signal recording. PLoS Comput Biol. 2013; 9(7):e1003145. View Abstract
  38. Robust circadian oscillations in growing cyanobacteria require transcriptional feedback. Science. 2013 May 10; 340(6133):737-40. View Abstract
  39. High degree of coordination and division of labor among subunits in a homomeric ring ATPase. Cell. 2012 Nov 21; 151(5):1017-28. View Abstract
  40. The single-cell chemostat: an agarose-based, microfluidic device for high-throughput, single-cell studies of bacteria and bacterial communities. Lab Chip. 2012 Apr 21; 12(8):1487-94. View Abstract
  41. Single-base pair unwinding and asynchronous RNA release by the hepatitis C virus NS3 helicase. Science. 2011 Sep 23; 333(6050):1746-9. View Abstract
  42. Time-gating improves the spatial resolution of STED microscopy. Opt Express. 2011 Feb 28; 19(5):4242-54. View Abstract
  43. Mechanistic constraints from the substrate concentration dependence of enzymatic fluctuations. Proc Natl Acad Sci U S A. 2010 Sep 07; 107(36):15739-44. View Abstract
  44. Mechanochemistry of a viral DNA packaging motor. J Mol Biol. 2010 Jul 09; 400(2):186-203. View Abstract
  45. Methods in statistical kinetics. Methods Enzymol. 2010; 475:221-57. View Abstract
  46. DNA based molecular motors. Phys Life Rev. 2009 Dec; 6(4):250-66. View Abstract
  47. Substrate interactions and promiscuity in a viral DNA packaging motor. Nature. 2009 Oct 01; 461(7264):669-73. View Abstract
  48. High-resolution dual-trap optical tweezers with differential detection: managing environmental noise. Cold Spring Harb Protoc. 2009 Oct; 2009(10):pdb.ip72. View Abstract
  49. High-resolution dual-trap optical tweezers with differential detection: instrument design. Cold Spring Harb Protoc. 2009 Oct; 2009(10):pdb.ip73. View Abstract
  50. High-resolution dual-trap optical tweezers with differential detection: data collection and instrument calibration. Cold Spring Harb Protoc. 2009 Oct; 2009(10):pdb.ip74. View Abstract
  51. High-resolution dual-trap optical tweezers with differential detection: minimizing the influence of measurement noise. Cold Spring Harb Protoc. 2009 Oct; 2009(10):pdb.ip75. View Abstract
  52. High-resolution dual-trap optical tweezers with differential detection: alignment of instrument components. Cold Spring Harb Protoc. 2009 Oct; 2009(10):pdb.ip76. View Abstract
  53. High-resolution dual-trap optical tweezers with differential detection: an introduction. Cold Spring Harb Protoc. 2009 Oct; 2009(10):pdb.top60. View Abstract
  54. Intersubunit coordination in a homomeric ring ATPase. Nature. 2009 Jan 22; 457(7228):446-50. View Abstract
  55. Exact solutions for kinetic models of macromolecular dynamics. J Phys Chem B. 2008 May 15; 112(19):6025-44. View Abstract
  56. Recent advances in optical tweezers. Annu Rev Biochem. 2008; 77:205-28. View Abstract
  57. Differential detection of dual traps improves the spatial resolution of optical tweezers. Proc Natl Acad Sci U S A. 2006 Jun 13; 103(24):9006-11. View Abstract
  58. Self-erasing perturbations of Abelian sandpiles. Phys Rev E Stat Nonlin Soft Matter Phys. 2004; 70(1 Pt 2):016203. View Abstract

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