Jordan Moore

All Publications

• Vasculogenic tissue nanotransfection accelerates functional recovery after peripheral nerve injury SCIENCE ADVANCES Salazar-Puerta, A. I., Kheirkhah, S., Stranan, J. P., Harris, H., Khattab, N., Fukuda, M., Barringer, G., Vasquez-Martinez, C. A., Cortes, S., Ott, N., Lawrence, W. R., Das, D., Moore, J. T., Saffari, T. M., Salazar-Gil, J. D., Alzate-Correa, D., Yu, J., Dathathreya, K., Higuita-Castro, N., Cuellar-Gaviria, T. Z., Arnold, W., Moore, A. M., Gallego Perez, D. 2026; 12 (15): eaeb7631

  Abstract

  Peripheral nerve injuries (PNIs) remain a major clinical challenge, often leaving patients with lifelong sensory, motor, and functional impairments despite surgical repair. While gene and cell therapies hold promise, their translation has been hampered by the lack of safe, efficient, and targeted delivery strategies. Here, we introduce vasculogenic tissue nanotransfection (TNT) as a nonviral, reprogramming-based therapeutic platform to enhance nerve regeneration to augment surgical reconstruction. This one-time, millisecond-scale intervention reprograms resident cells in situ toward a vasculogenic phenotype, fostering neovascularization and vascular remodeling to support axonal regeneration. Through integrated in vitro screening and in vivo validation, we identified an optimized formulation of vasculogenic genes (Etv2, Fli1, and Foxc2; EFF) that maximized reprogramming efficiency and regenerative potential. In a long-segment nerve defect model reconstructed with isografts, TNT-mediated delivery of EFF markedly improved functional recovery, including grip strength and muscle contractility, accompanied by increased vascular density and myelinated axon counts. Together, these findings establish TNT-mediated vasculogenic reprogramming as a transformative adjunct to surgical repair of PNIs, offering a clinically translatable strategy to accelerate nerve regeneration and restore function.

  View details for DOI 10.1126/sciadv.aeb7631

  View details for Web of Science ID 001736060700005

  View details for PubMedID 41950328

  View details for PubMedCentralID PMC13060591

• Unlocking the power of virtual networking for early-career researchers. eLife Hayes, C. A., Moore, J. T., Headley, C. A., Berrios-Negron, A. L., Lambert, W. M. 2024; 13

  Abstract

  Many successful researchers in the biomedical sciences have benefitted from mentors and networks earlier in their career. However, early-career researchers from minoritized and underrepresented groups do not have the same access to potential mentors and networks as many of their peers. In this article we describe how 'cold emails' and social media platforms - notably Twitter/X and LinkedIn - can be used to build virtual networks, and stress the need to invest in maintaining networks once they have been established.

  View details for DOI 10.7554/eLife.96381

  View details for PubMedID 38501601

• Injectable pulverized electrospun poly(lactic-co-glycolic acid) fibers improve human adipose tissue engraftment and volume retention. Journal of biomedical materials research. Part A Das, D., Lawrence, W. R., Diaz-Starokozheva, L., Salazar-Puerta, A. I., Ott, N., Goebel, E. R., Damughatla, A., Vidal, P., Gallentine, S., Moore, J. T., Kayuha, D., Mendonca, N. C., Albert, J. B., Houser, R., Johnson, J., Powell, H., Higuita-Castro, N., Stanford, K. I., Gallego-Perez, D. 2023; 111 (11): 1722-1733

  Abstract

  Autologous adipose tissue is commonly used for tissue engraftment for the purposes of soft tissue reconstruction due to its relative abundance in the human body and ease of acquisition using liposuction methods. This has led to the adoption of autologous adipose engraftment procedures that allow for the injection of adipose tissues to be used as a "filler" for correcting cosmetic defects and deformities in soft tissues. However, the clinical use of such methods has several limitations, including high resorption rates and poor cell survivability, which lead to low graft volume retention and inconsistent outcomes. Here, we describe a novel application of milled electrospun poly(lactic-co-glycolic acid) (PLGA) fibers, which can be co-injected with adipose tissue to improve engraftment outcomes. These PLGA fibers had no significant negative impact on the viability of adipocytes in vitro and did not elicit long-term proinflammatory responses in vivo. Furthermore, co-delivery of human adipose tissue with pulverized electrospun PLGA fibers led to significant improvements in reperfusion, vascularity, and retention of graft volume compared to injections of adipose tissue alone. Taken together, the use of milled electrospun fibers to enhance autologous adipose engraftment techniques represents a novel approach for improving upon the shortcomings of such methods.

  View details for DOI 10.1002/jbm.a.37581

  View details for PubMedID 37326365

  View details for PubMedCentralID PMC10527741

• Identification of a physiologic vasculogenic fibroblast state to achieve tissue repair. Nature communications Pal, D., Ghatak, S., Singh, K., Abouhashem, A. S., Kumar, M., El Masry, M. S., Mohanty, S. K., Palakurti, R., Rustagi, Y., Tabasum, S., Khona, D. K., Khanna, S., Kacar, S., Srivastava, R., Bhasme, P., Verma, S. S., Hernandez, E., Sharma, A., Reese, D., Verma, P., Ghosh, N., Gorain, M., Wan, J., Liu, S., Liu, Y., Castro, N. H., Gnyawali, S. C., Lawrence, W., Moore, J., Perez, D. G., Roy, S., Yoder, M. C., Sen, C. K. 2023; 14 (1): 1129

  Abstract

  Tissue injury to skin diminishes miR-200b in dermal fibroblasts. Fibroblasts are widely reported to directly reprogram into endothelial-like cells and we hypothesized that miR-200b inhibition may cause such changes. We transfected human dermal fibroblasts with anti-miR-200b oligonucleotide, then using single cell RNA sequencing, identified emergence of a vasculogenic subset with a distinct fibroblast transcriptome and demonstrated blood vessel forming function in vivo. Anti-miR-200b delivery to murine injury sites likewise enhanced tissue perfusion, wound closure, and vasculogenic fibroblast contribution to perfused vessels in a FLI1 dependent manner. Vasculogenic fibroblast subset emergence was blunted in delayed healing wounds of diabetic animals but, topical tissue nanotransfection of a single anti-miR-200b oligonucleotide was sufficient to restore FLI1 expression, vasculogenic fibroblast emergence, tissue perfusion, and wound healing. Augmenting a physiologic tissue injury adaptive response mechanism that produces a vasculogenic fibroblast state change opens new avenues for therapeutic tissue vascularization of ischemic wounds.

  View details for DOI 10.1038/s41467-023-36665-z

  View details for PubMedID 36854749

  View details for PubMedCentralID PMC9975176

• Characterizing CD38 Expression and Enzymatic Activity in the Brain of Spontaneously Hypertensive Stroke-Prone Rats. Frontiers in pharmacology Hannawi, Y., Ewees, M. G., Moore, J. T., Zweier, J. L. 2022; 13: 881708

  Abstract

  Background: CD38 is a transmembrane glycoprotein that catabolizes nicotinamide adenine dinucleotide (NAD+) and is the main source for the age-dependent decrease in NAD+ levels. Increased CD38 enzymatic activity has been implicated in several neurological diseases. However, its role in the pathogenesis of cerebral small vessel disease (CSVD) remains unknown. We aimed to characterize CD38 expression and enzymatic activity in the brain of spontaneously hypertensive stroke-prone rats (SHRSP), a genetic model for hypertension and human CSVD, in comparison to age-matched normotensive Wistar Kyoto rats (WKY). Materials and Methods: Age-matched male 7- and 24-week-old WKY and SHRSP were studied. CD38 enzymatic activity was determined in the brain homogenate. Immunohistochemistry and Western Blotting (WB) were used to characterize CD38 expression and localize it in the different cell types within the brain. In addition, expression of nitric oxide synthase (NOS) isoforms and the levels of nitric oxide (NO), superoxide, nicotinamide dinucleotide (phosphate) NAD(P)H were measured the brain of in WKY and SHRSP. Results: CD38 expression and enzymatic activity were increased in SHRSP brains compared to age matched WKY starting at 7 weeks of age. CD38 expression was localized to the endothelial cells, astrocytes, and microglia. We also identified increased CD38 expression using WB with age in SHRSP and WKY. CD38 enzymatic activity was also increased in 24-week SHRSP compared to 7-week SHRSP. In association, we identified evidence of oxidative stress, reduced NO level, reduced NAD(P)H level and endothelial NOS expression in SHRSP compared to age matched WKY. NAD(P)H also decreased with age in WKY and SHRSP. Additionally, activation of astrocytes and microglia were present in SHRSP compared to WKY. Conclusions: CD38 is overexpressed, and its enzymatic activity is increased in SHRSP, a genetic model for marked hypertension and human CSVD. Our results suggest a potential role for CD38 enzymatic activation in the pathogenesis of CSVD and points to the need for future mechanistic and pharmacological studies.

  View details for DOI 10.3389/fphar.2022.881708

  View details for PubMedID 35712720

  View details for PubMedCentralID PMC9194821

• In Situ Deployment of Engineered Extracellular Vesicles into the Tumor Niche via Myeloid-Derived Suppressor Cells. Advanced healthcare materials Duarte-Sanmiguel, S., Panic, A., Dodd, D. J., Salazar-Puerta, A., Moore, J. T., Lawrence, W. R., Nairon, K., Francis, C., Zachariah, N., McCoy, W., Turaga, R., Skardal, A., Carson, W. E., Higuita-Castro, N., Gallego-Perez, D. 2022; 11 (5): e2101619

  Abstract

  Extracellular vesicles (EVs) have emerged as a promising carrier system for the delivery of therapeutic payloads in multiple disease models, including cancer. However, effective targeting of EVs to cancerous tissue remains a challenge. Here, it is shown that nonviral transfection of myeloid-derived suppressor cells (MDSCs) can be leveraged to drive targeted release of engineered EVs that can modulate transfer and overexpression of therapeutic anticancer genes in tumor cells and tissue. MDSCs are immature immune cells that exhibit enhanced tropism toward tumor tissue and play a role in modulating tumor progression. Current MDSC research has been mostly focused on mitigating immunosuppression in the tumor niche; however, the tumor homing abilities of these cells present untapped potential to deliver EV therapeutics directly to cancerous tissue. In vivo and ex vivo studies with murine models of breast cancer show that nonviral transfection of MDSCs does not hinder their ability to home to cancerous tissue. Moreover, transfected MDSCs can release engineered EVs and mediate antitumoral responses via paracrine signaling, including decreased invasion/metastatic activity and increased apoptosis/necrosis. Altogether, these findings indicate that MDSCs can be a powerful tool for the deployment of EV-based therapeutics to tumor tissue.

  View details for DOI 10.1002/adhm.202101619

  View details for PubMedID 34662497

  View details for PubMedCentralID PMC8891033

• Nanochannel-Based Poration Drives Benign and Effective Nonviral Gene Delivery to Peripheral Nerve Tissue. Advanced biosystems Moore, J. T., Wier, C. G., Lemmerman, L. R., Ortega-Pineda, L., Dodd, D. J., Lawrence, W. R., Duarte-Sanmiguel, S., Dathathreya, K., Diaz-Starokozheva, L., Harris, H. N., Sen, C. K., Valerio, I. L., Higuita-Castro, N., Arnold, W. D., Kolb, S. J., Gallego-Perez, D. 2020; 4 (11): e2000157

  Abstract

  While gene and cell therapies have emerged as promising treatment strategies for various neurological conditions, heavy reliance on viral vectors can hamper widespread clinical implementation. Here, the use of tissue nanotransfection as a platform nanotechnology to drive nonviral gene delivery to nerve tissue via nanochannels, in an effective, controlled, and benign manner is explored. TNT facilitates plasmid DNA delivery to the sciatic nerve of mice in a voltage-dependent manner. Compared to standard bulk electroporation (BEP), impairment in toe-spread and pinprick response is not caused by TNT, and has limited to no impact on electrophysiological parameters. BEP, however, induces significant nerve damage and increases macrophage immunoreactivity. TNT is subsequently used to deliver vasculogenic cell therapies to crushed nerves via delivery of reprogramming factor genes Etv2, Foxc2, and Fli1 (EFF). The results indicate the TNT-based delivery of EFF in a sciatic nerve crush model leads to increased vascularity, reduced macrophage infiltration, and improved recovery in electrophysiological parameters compared to crushed nerves that are TNT-treated with sham/empty plasmids. Altogether, the results indicate that TNT can be a powerful platform nanotechnology for localized nonviral gene delivery to nerve tissue, in vivo, and the deployment of reprogramming-based cell therapies for nerve repair/regeneration.

  View details for DOI 10.1002/adbi.202000157

  View details for PubMedID 32939985

  View details for PubMedCentralID PMC7704786

• Reciprocal Signaling between Myeloid Derived Suppressor and Tumor Cells Enhances Cellular Motility and is Mediated by Structural Cues in the Microenvironment. Advanced biosystems Shukla, V. C., Duarte-Sanmiguel, S., Panic, A., Senthilvelan, A., Moore, J., Bobba, C., Benner, B., Carson, W. E., Ghadiali, S. N., Gallego-Perez, D. 2020; 4 (6): e2000049

  Abstract

  Myeloid derived suppressor cells (MDSCs) have gained significant attention for their immunosuppressive role in cancer and their ability to contribute to tumor progression and metastasis. Understanding the role of MDSCs in driving cancer cell migration, a process fundamental to metastasis, is essential to fully comprehend and target MDSC-tumor cell interactions. This study employs microfabricated platforms, which simulate the structural cues present in the tumor microenvironment (TME) to elucidate the effects of MDSCs on the migratory phenotype of cancer cells at the single cell level. The results indicate that the presence of MDSCs enhances the motility of cancer-epithelial cells when directional cues (either topographical or spatial) are present. This behavior appears to be independent of cell-cell contact and driven by soluble byproducts from heterotypic interactions between MDSCs and cancer cells. Moreover, MDSC cell-motility is also impacted by the presence of cancer cells and the cancer cell secretome in the presence of directional cues. Epithelial dedifferentiation is the likely mechanism for changes in cancer cell motility in response to MDSCs. These results highlight the biochemical and biostructural conditions under which MDSCs can support cancer cell migration, and could therefore provide new avenues of research and therapy aimed at stemming cancer progression.

  View details for DOI 10.1002/adbi.202000049

  View details for PubMedID 32419350

  View details for PubMedCentralID PMC7489303

• Guided migration analyses at the single-clone level uncover cellular targets of interest in tumor-associated myeloid-derived suppressor cell populations. Scientific reports Duarte-Sanmiguel, S., Shukla, V., Benner, B., Moore, J., Lemmerman, L., Lawrence, W., Panic, A., Wang, S., Idzkowski, N., Guio-Vega, G., Higuita-Castro, N., Ghadiali, S., Carson, W. E., Gallego-Perez, D. 2020; 10 (1): 1189

  Abstract

  Myeloid-derived suppressor cells (MDSCs) are immune cells that exert immunosuppression within the tumor, protecting cancer cells from the host's immune system and/or exogenous immunotherapies. While current research has been mostly focused in countering MDSC-driven immunosuppression, little is known about the mechanisms by which MDSCs disseminate/infiltrate cancerous tissue. This study looks into the use of microtextured surfaces, coupled with in vitro and in vivo cellular and molecular analysis tools, to videoscopically evaluate the dissemination patterns of MDSCs under structurally guided migration, at the single-cell level. MDSCs exhibited topographically driven migration, showing significant intra- and inter-population differences in motility, with velocities reaching ~40 μm h-1. Downstream analyses coupled with single-cell migration uncovered the presence of specific MDSC subpopulations with different degrees of tumor-infiltrating and anti-inflammatory capabilities. Granulocytic MDSCs showed a ~≥3-fold increase in maximum dissemination velocities and traveled distances, and a ~10-fold difference in the expression of pro- and anti-inflammatory markers. Prolonged culture also revealed that purified subpopulations of MDSCs exhibit remarkable plasticity, with homogeneous/sorted subpopulations giving rise to heterogenous cultures that represented the entire hierarchy of MDSC phenotypes within 7 days. These studies point towards the granulocytic subtype as a potential cellular target of interest given their superior dissemination ability and enhanced anti-inflammatory activity.

  View details for DOI 10.1038/s41598-020-57941-8

  View details for PubMedID 31988310

  View details for PubMedCentralID PMC6985212

• Topical tissue nano-transfection mediates non-viral stroma reprogramming and rescue. Nature nanotechnology Gallego-Perez, D., Pal, D., Ghatak, S., Malkoc, V., Higuita-Castro, N., Gnyawali, S., Chang, L., Liao, W. C., Shi, J., Sinha, M., Singh, K., Steen, E., Sunyecz, A., Stewart, R., Moore, J., Ziebro, T., Northcutt, R. G., Homsy, M., Bertani, P., Lu, W., Roy, S., Khanna, S., Rink, C., Sundaresan, V. B., Otero, J. J., Lee, L. J., Sen, C. K. 2017; 12 (10): 974-979

  Abstract

  Although cellular therapies represent a promising strategy for a number of conditions, current approaches face major translational hurdles, including limited cell sources and the need for cumbersome pre-processing steps (for example, isolation, induced pluripotency). In vivo cell reprogramming has the potential to enable more-effective cell-based therapies by using readily available cell sources (for example, fibroblasts) and circumventing the need for ex vivo pre-processing. Existing reprogramming methodologies, however, are fraught with caveats, including a heavy reliance on viral transfection. Moreover, capsid size constraints and/or the stochastic nature of status quo approaches (viral and non-viral) pose additional limitations, thus highlighting the need for safer and more deterministic in vivo reprogramming methods. Here, we report a novel yet simple-to-implement non-viral approach to topically reprogram tissues through a nanochannelled device validated with well-established and newly developed reprogramming models of induced neurons and endothelium, respectively. We demonstrate the simplicity and utility of this approach by rescuing necrotizing tissues and whole limbs using two murine models of injury-induced ischaemia.

  View details for DOI 10.1038/nnano.2017.134

  View details for PubMedID 28785092

  View details for PubMedCentralID PMC5814120