Contact

  • Academic
    University - Academic staff Department: Department of Molecular and Cellular Physiology Position: Basic Life Research Scientist

Additional Info

  • Mail Code: 4060
  • Other Names:
    G. Edward Marti
    Edward Marti

All Publications

  • Nanometer-resolution tracking of single cargo reveals dynein motor mechanisms. Nature chemical biology Peng, C. S., Zhang, Y., Liu, Q., Marti, G. E., Huang, Y. A., Sudhof, T. C., Cui, B., Chu, S. 2024

    Abstract

    Cytoplasmic dynein is essential for intracellular transport. Despite extensive in vitro characterizations, how the dynein motors transport vesicles by processive steps in live cells remains unclear. To dissect the molecular mechanisms of dynein, we develop optical probes that enable long-term single-particle tracking in live cells with high spatiotemporal resolution. We find that the number of active dynein motors transporting cargo switches stochastically between one and five dynein motors during long-range transport in neuronal axons. Our very bright optical probes allow the observation of individual molecular steps. Strikingly, these measurements reveal that the dwell times between steps are controlled by two temperature-dependent rate constants in which two ATP molecules are hydrolyzed sequentially during each dynein step. Thus, our observations uncover a previously unknown chemomechanical cycle of dynein-mediated cargo transport in living cells.

    View details for DOI 10.1038/s41589-024-01694-2

    View details for PubMedID 39090313

  • AZGP1 deficiency promotes angiogenesis in prostate cancer. Journal of translational medicine Wen, R. M., Qiu, Z., Marti, G. E., Peterson, E. E., Marques, F. J., Bermudez, A., Wei, Y., Nolley, R., Lam, N., Polasko, A. L., Chiu, C. L., Zhang, D., Cho, S., Karageorgos, G. M., McDonough, E., Chadwick, C., Ginty, F., Jung, K. J., Machiraju, R., Mallick, P., Crowley, L., Pollack, J. R., Zhao, H., Pitteri, S. J., Brooks, J. D. 2024; 22 (1): 383

    Abstract

    Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive.AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1± mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples.Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1-/- mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues.AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.

    View details for DOI 10.1186/s12967-024-05183-x

    View details for PubMedID 38659028

    View details for PubMedCentralID 321763

  • Siglec-7/9 are novel immune checkpoints for prostate cancer Wen, R., Stark, J. C., Marti, G., Garcia-Marques, F., Zhao, H., Nolley, R., Bertozzi, C. R., Pitteri, S. J., Brooks, J. D. AMER ASSOC IMMUNOLOGISTS. 2023

    View details for DOI 10.4049/jimmunol.210.Supp.89.13

    View details for Web of Science ID 001106506501123

  • Precision Metrology Meets Cosmology: Improved Constraints on Ultralight Dark Matter from Atom-Cavity Frequency Comparisons PHYSICAL REVIEW LETTERS Kennedy, C. J., Oelker, E., Robinson, J. M., Bothwell, T., Kedar, D., Milner, W. R., Marti, G., Derevianko, A., Ye, J. 2020; 125 (20)

    View details for DOI 10.1103/PhysRevLett.125.201302

    View details for Web of Science ID 000588592900004

  • Engineering Quantum States of Matter for Atomic Clocks in Shallow Optical Lattices PHYSICAL REVIEW LETTERS Hutson, R. B., Goban, A., Marti, G., Sonderhouse, L., Sanner, C., Ye, J. 2019; 123 (12)

    View details for DOI 10.1103/PhysRevLett.123.123401

    View details for Web of Science ID 000486655100006