All Publications


  • Nanoparticles as Cell Tracking Agents in Human Ocular Cell Transplantation Therapy CURRENT OPHTHALMOLOGY REPORTS Mundy, D. C., Goldberg, J. L. 2021
  • Supramolecular host-guest hyaluronic acid hydrogels enhance corneal wound healing through dynamic spatiotemporal effects. The ocular surface Fernandes-Cunha, G. M., Jeong, S. H., Logan, C. M., Le, P., Mundy, D., Chen, F., Chen, K. M., Kim, M., Lee, G., Na, K., Hahn, S. K., Myung, D. 2021

    Abstract

    Large abrasions and deeper ulcers of the cornea can lead to corneal scarring, ulceration and thinning if not promptly and adequately treated. Hyaluronic acid (HA) has been investigated for the treatment of corneal wounds due to its remarkable biocompatibility, transparency and mucoadhesive properties. However, intact linear HA has low retention time on the cornea and chemical crosslinkers to synthesize HA hydrogels can cause toxicity limiting their clinical ocular applications. Here, we used supramolecular HA hydrogels formed by non-covalent host-guest interactions between HA-cyclodextrin and HA-adamantane to evaluate the impact of the hydrogels on corneal wound healing. Supramolecular HA hydrogels facilitated adhesion and spreading of encapsulated human corneal epithelial cells ex vivo and improved corneal wound healing in vivo as an in situ-formed, acellular therapeutic membrane. The HA hydrogels were absorbed within the corneal stroma over time, modulated mesenchymal cornea stromal cell secretome production, reduced cellularity and inflammation of the anterior stroma, and significantly mitigated corneal edema compared to treatment with linear HA and untreated control eyes. Taken together, our results demonstrate supramolecular HA hydrogels as a promising and versatile biomaterial platform for corneal wound healing.

    View details for DOI 10.1016/j.jtos.2021.09.002

    View details for PubMedID 34537415

  • Landscape of innate lymphoid cells in human head and neck cancer reveals divergent NK cell states in the tumor microenvironment. Proceedings of the National Academy of Sciences of the United States of America Moreno-Nieves, U. Y., Tay, J. K., Saumyaa, S., Horowitz, N. B., Shin, J. H., Mohammad, I. A., Luca, B., Mundy, D. C., Gulati, G. S., Bedi, N., Chang, S., Chen, C., Kaplan, M. J., Rosenthal, E. L., Holsinger, F. C., Divi, V., Baik, F. M., Sirjani, D. B., Gentles, A. J., Newman, A. M., Freud, A. G., Sunwoo, J. B. 2021; 118 (28)

    Abstract

    Natural killer (NK) cells comprise one subset of the innate lymphoid cell (ILC) family. Despite reported antitumor functions of NK cells, their tangible contribution to tumor control in humans remains controversial. This is due to incomplete understanding of the NK cell states within the tumor microenvironment (TME). Here, we demonstrate that peripheral circulating NK cells differentiate down two divergent pathways within the TME, resulting in different end states. One resembles intraepithelial ILC1s (ieILC1) and possesses potent in vivo antitumor activity. The other expresses genes associated with immune hyporesponsiveness and has poor antitumor functional capacity. Interleukin-15 (IL-15) and direct contact between the tumor cells and NK cells are required for the differentiation into CD49a+CD103+ cells, resembling ieILC1s. These data explain the similarity between ieILC1s and tissue-resident NK cells, provide insight into the origin of ieILC1s, and identify the ieILC1-like cell state within the TME to be the NK cell phenotype with the greatest antitumor activity. Because the proportions of the different ILC states vary between tumors, these findings provide a resource for the clinical study of innate immune responses against tumors and the design of novel therapy.

    View details for DOI 10.1073/pnas.2101169118

    View details for PubMedID 34244432

  • Supramolecular host-guest hyaluronic acid hydrogels for corneal endothelial cell delivery and epithelial wound healing Logan, C. M., Fernandes-Cunha, G., Jung, S., Le, P., Mundy, D. C., Kim, M., Lee, G., Hahn, S., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • In vitro characterization of a novel in situ-forming semi-interpenetrating polymer network of crosslinked collagen and glycosaminoglycans for corneal defect repair Mundy, D., Chen, F., Le, P., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • Collagen gels crosslinked by photoactivation of riboflavin for corneal defect repair Seo, Y., Fernandes-Cunha, G., Chen, F., Le, P., Logan, C., Mundy, D., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • In situ-forming semi-interpenetrating network hydrogels for corneal regeneration: in vivo biological response Chen, F., Le, P., Fernandes-Cunha, G., Mundy, D., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • In situ forming collagen-PEG hydrogel as a matrix therapy for corneal defects: 2 month in vivo response Rogers, G., Chen, F., Le, P., Mundy, D., Logan, C., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • 3D Printable, Modified Trephine Designs for Consistent Anterior Lamellar Keratectomy Wounds in Rabbits. Current eye research Chen, F., Buickians, D., Le, P., Xia, X., Montague-Alamin, S. Q., Blanco Varela, I. B., Mundy, D. C., Logan, C. M., Myung, D. 2021: 1–10

    Abstract

    Purpose: Our goal is to develop a low-cost tool that can be used to create consistent, partial-thickness defects in rabbit and other large animals with minimal surgical training and that can facilitate pre-clinical testing of lamellar and in situ-forming biosynthetic matrix materials for corneal repair. Materials & Methods: In this study, three modified trephines were designed to create deep corneal wound defects with consistent depth in large animals. The modified trephines incorporated either 3D-printed parts made from photopolymerizable resins, or custom-cut commercially available Teflon sheets. Wound defects were imaged with optical coherence tomography (OCT), and the depth was analyzed based on the OCT images. Results: The results revealed that an inner-stopper guard trephine had the best performance in creating consistent and precise wound defect depth compared to modified vacuum trephine and custom guard vacuum trephine. A 75% ± 10% cut of the cornea was achieved with the inner-stopper guard trephine. The wound defect depth by created by the inner-stopper guard trephine was independent of the corneal thickness or size of the globes. Although the cut depth of the inner-stopper guard trephine differed by the experience-level of its users, the consistency (standard deviation) of the depth was independent of experience. Conclusions: Our studies provided three cost-efficient animal trephines that can create corneal wounds of consistent depth by lab researchers without extensive training in keratectomy.

    View details for DOI 10.1080/02713683.2020.1868010

    View details for PubMedID 33474996

  • Plasticity and Polarization of Human NK Cells in the Tumor Microenvironment Nieves, U., Tay, J., Saumyaa, S., Mundy, D., Sunwoo, J. B. AMER ASSOC IMMUNOLOGISTS. 2020
  • The use of platelet-rich plasma in treatment of olfactory dysfunction: A pilot study. Laryngoscope investigative otolaryngology Yan, C. H., Mundy, D. C., Patel, Z. M. 2020; 5 (2): 187–93

    Abstract

    Olfactory dysfunction is a prevalent problem with a significant impact on quality of life and increased mortality. Limited effective therapies exist. Platelet-rich plasma (PRP) is an autologous biologic product with anti-inflammatory and neuroprotective effects. This novel pilot study evaluated the role of PRP on olfactory neuroregeneration in patients with hyposmia.Seven patients who had olfactory loss greater than 6 months in duration, no evidence of sinonasal inflammatory disease, and no improvement with olfactory training and budesonide topical rinses were enrolled in this preliminary study. Patients received a single intranasal injection of PRP into the mucosa of the olfactory cleft. The Sniffin' Sticks olfactory test consisting of threshold, discrimination, and identification measurements (TDI) was administered at the beginning of the study and at 1 and 3 months.All patients reported a subjective improvement of their smell shortly after injection but then stabilized. At 3-month post-treatment, two patients with functional anosmia (TDI < 16) did not improve significantly. Five patients with hyposmia (TDI > 16 but <30) showed an improvement with 60% achieving normosmia (TDI > 30) at 3-month follow-up. On average, patients with baseline TDI > 16 improved by 5.85 points with the most significant improvement in the threshold subcomponent. There were no adverse outcomes from intranasal PRP injections.PRP appears safe for use in the treatment of olfactory loss, and preliminary data suggest possible efficacy, especially for those with moderate yet persistent loss. Further studies will help determine optimal frequency and duration of use.

    View details for DOI 10.1002/lio2.357

    View details for PubMedID 32337347

    View details for PubMedCentralID PMC7178450

  • Assessing the Impact of Targeting CEACAM1 in Head and Neck Squamous Cell Carcinoma Tam, K., Schoppy, D. W., Shin, J., Tay, J. K., Moreno-Nieves, U., Mundy, D. C., Sunwoo, J. B. SAGE PUBLICATIONS LTD. 2018: 76–84
  • The aryl hydrocarbon receptor modulates the function of human CD56(bright) NK cells EUROPEAN JOURNAL OF IMMUNOLOGY Moreno-Nieves, U. Y., Mundy, D. C., Shin, J., Tam, K., Sunwoo, J. B. 2018; 48 (5): 771–76
  • The aryl hydrocarbon receptor modulates the function of human CD56bright NK cells. European journal of immunology Moreno-Nieves, U. Y., Mundy, D. C., Shin, J. H., Tam, K. n., Sunwoo, J. B. 2018

    Abstract

    Human natural killer (NK) cells are divided into two subsets: CD56bright and CD56dim NK cells, which differ in maturation, function and distribution. Mechanisms regulating NK cell functions are not completely understood. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, that binds to a variety of endogenous and exogenous molecules, and that has recently been shown to modulate the function and differentiation of immune cells. Here, we studied the expression of AhR and its involvement in the regulation of NK cell functions. We found that AhR mRNA is highly expressed in peripheral CD56bright NK cells and that AhR mRNA expression gradually decreases as NK cells display a more mature phenotype. CD56bright NK cells were highly sensitive to AhR ligands. Specifically, AhR ligands modulated their activation and their expression of NK cell receptors, as well as cytokine secretion which is the major function of these cells. As CD56bright NK cells are highly enriched in tissues and in tumors, our observations point to a possible effect of local AhR ligands in the regulation of the function of CD56bright tissue-resident or intratumoral NK cells. This article is protected by copyright. All rights reserved.

    View details for PubMedID 29336030

  • Assessing the Impact of Targeting CEACAM1 in Head and Neck Squamous Cell Carcinoma. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery Tam, K. n., Schoppy, D. W., Shin, J. H., Tay, J. K., Moreno-Nieves, U. n., Mundy, D. C., Sunwoo, J. B. 2018: 194599818756627

    Abstract

    Objective In conjunction with advances made in cytotoxic chemotherapy, radiation, and surgery, immunotherapy has emerged as a fourth modality of treatment for head and neck squamous cell carcinoma (HNSCC). Understanding the mechanisms by which HNSCC evades immune-mediated control will aid in the development of new therapies to augment an antitumor immune response. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a cell surface receptor that is expressed on malignant cells and lymphocytes such as natural killer (NK) cells. We sought to determine whether tumor-derived CEACAM1 inhibits NK cell cytotoxicity and whether blockade of CEACAM1 restores antitumor immunity. Study Design In vitro HNSCC cell line study. Setting Research laboratory. Subject and Methods We utilized a real-time cell analyzer to assess NK cell cytotoxicity against an oral squamous cell carcinoma cell line after modulating CEACAM1 expression by cytokines and shRNA knockdown of CEACAM1 expression. Results NK cells and HNSCC cells both demonstrated cytokine-inducible expression of CEACAM1. Coincubation of NK cells and HNSCC cells resulted in the upregulation of CEACAM1 on the tumor cells. When compared with CEACAM1-cells, CEACAM1+tumor cells exhibited increased cell growth and increased size and number of organoids in 3-dimensional culture. Notably, CEACAM1+HNSCC cells were more resistant to NK cell-mediated killing, but the inhibited expression of CEACAM1 by an shRNA construct restored NK cell cytotoxicity. Conclusion Together, these data indicate that CEACAM1 acts as an inducible checkpoint molecule, and they support the idea that targeting CEACAM1 could serve as a novel immunotherapy approach in HNSCC.

    View details for PubMedID 29436278