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Gill Diamond   Dr.  Senior Scientist or Principal Investigator 
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Gill Diamond published an article in October 2018.
Research Keywords & Expertise
0 A
0 antimicrobial peptides
0 antimicrobial activity
Top co-authors See all
Richard W. Scott

7 shared publications

Fox Chase Chemical Diversity Center, Inc., Pennsylvania Biotechnology Center, Doylestown, PA 18902, USA

Lisa Kathleen Ryan

3 shared publications

The Public Health Research Institute Center, Rutgers New Jersey Medical School, Newark, NJ 07103, USA

Jeffrey C. Pelletier

2 shared publications

Fox Chase Chemical Diversity Center, Inc., 3805 Old Easton Road, Doylestown, Pennsylvania 18902, United States

Jorge A. Masso-Silva

2 shared publications

Department of Oral Biology, Rutgers School of Dental Medicine, Newark, New Jersey, USA

Damian G. Weaver

1 shared publications

Fox Chase Chemical Diversity Center, Inc., Pennsylvania Biotechnology Center, Doylestown, PA 18902, USA

15
Publications
19
Reads
11
Downloads
120
Citations
Publication Record
Distribution of Articles published per year 
(2003 - 2018)
Total number of journals
published in
 
13
 
Publications See all
Article 0 Reads 0 Citations LL-37 disrupts the Kaposi's sarcoma-associated herpesvirus envelope and inhibits infection in oral epithelial cells David C. Brice, Zsolt Toth, Gill Diamond Published: 01 October 2018
Antiviral Research, doi: 10.1016/j.antiviral.2018.07.025
DOI See at publisher website
Article 0 Reads 0 Citations β-Defensins Coordinate In Vivo to Inhibit Bacterial Infections of the Trachea Lisa Kathleen Ryan, Jichuan Wu, Kyell Schwartz, Sunghan Yim,... Published: 28 August 2018
Vaccines, doi: 10.3390/vaccines6030057
DOI See at publisher website ABS Show/hide abstract
β-defensins are predicted to play an important role in innate immunity against bacterial infections in the airway. We previously observed that a type III-secretion product of Bordetella bronchiseptica inhibits the NF-κB-mediated induction of a β-defensin in airway epithelial cells in vitro. To confirm this in vivo and to examine the relative roles of other β-defensins in the airway, we infected wild-type C57BL/6 mice and mice with a deletion of the mBD-1 gene with B. bronchiseptica wild-type strain, RB50 and its mutant strain lacking the type III-secretion system, WD3. The bacteria were quantified in the trachea and the nasal tissue and mRNA levels of mouse β-defensin-3 (mBD-3) were assessed after 24 h. Infection with the wild-type bacterial strain resulted in lower mBD-3 mRNA levels in the trachea than in mice infected with the type III-deficient strain. Furthermore, we observed an increase in bacterial numbers of RB50 only in the tracheas of mBD-1-deficient mice. Neutrophils were also more abundant on the trachea in RB50 infected WT mice but not in the bronchiolar lavage fluid (BAL), compared with WD3 infected WT and mBD-1−/− mice, indicating that the coordination of β-defensin chemotactic effects may be confined to tracheal epithelial cells (TEC). RB50 decreased the ability of mice to mount an early specific antibody response, seven days after infection in both WT and mBD-1−/− mice but there were no differences in titers between RB50-infected WT and mBD-1−/− mice or between WD3-infected WT and mBD-1−/− mice, indicating mBD-1 was not involved in induction of the humoral immune response to the B. bronchiseptica. Challenge of primary mouse TEC in vitro with RB50 and WD3, along with IL-1β, further corroborated the in vivo studies. The results demonstrate that at least two β-defensins can coordinate early in an infection to limit the growth of bacteria in the trachea.
Article 1 Read 0 Citations Antifungal Potential of Host Defense Peptide Mimetics in a Mouse Model of Disseminated Candidiasis Mobaswar Hossain Chowdhury, Lisa Kathleen Ryan, Kartikeya Ch... Published: 27 February 2018
Journal of Fungi, doi: 10.3390/jof4010030
DOI See at publisher website ABS Show/hide abstract
Invasive candidiasis caused by Candida albicans and non-albicans Candida (NAC) present a serious disease threat. Although the echinocandins are recommended as the first line of antifungal drug class, resistance to these agents is beginning to emerge, demonstrating the need for new antifungal agents. Host defense peptides (HDP) exhibit potent antifungal activity, but as drugs they are difficult to manufacture efficiently, and they are often inactivated by serum proteins. HDP mimetics are low molecular weight non-peptide compounds that can alleviate these problems and were shown to be membrane-active against C. albicans and NAC. Here, we expand upon our previous works to describe the in vitro and in vivo activity of 11 new HDP mimetics that are active against C. albicans and NAC that are both sensitive and resistant to standard antifungal drugs. These compounds exhibit minimum inhibitory/fungicidal concentration (MIC/MFC) in the µg/mL range in the presence of serum and are inhibited by divalent cations. Rapid propidium iodide influx into the yeast cells following in vitro exposure suggested that these HDP mimetics were also membrane active. The lead compounds were able to kill C. albicans in an invasive candidiasis CD-1 mouse model with some mimetic candidates decreasing kidney burden by 3–4 logs after 24 h in a dose-dependent manner. The data encouraged further development of this new anti-fungal drug class for invasive candidiasis.
Article 0 Reads 1 Citation Induction of CFTR gene expression by 1,25(OH) 2 vitamin D 3 , 25OH vitamin D 3 , and vitamin D 3 in cultured human airwa... Kristina M. DiFranco, Jennifer K. Mulligan, Aman S. Sumal, G... Published: 01 October 2017
The Journal of Steroid Biochemistry and Molecular Biology, doi: 10.1016/j.jsbmb.2017.01.013
DOI See at publisher website PubMed View at PubMed
Article 0 Reads 2 Citations Potent in vitro and in vivo antifungal activity of a small molecule host defense peptide mimic through a membrane-active... Lorenzo P. Menzel, Hossain Mobaswar Chowdhury, Jorge Adrian ... Published: 28 June 2017
Scientific Reports, doi: 10.1038/s41598-017-04462-6
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
Lethal systemic fungal infections of Candida species are increasingly common, especially in immune compromised patients. By in vitro screening of small molecule mimics of naturally occurring host defense peptides (HDP), we have identified several active antifungal molecules, which also exhibited potent activity in two mouse models of oral candidiasis. Here we show that one such compound, C4, exhibits a mechanism of action that is similar to the parent HDP upon which it was designed. Specifically, its initial interaction with the anionic microbial membrane is electrostatic, as its fungicidal activity is inhibited by cations. We observed rapid membrane permeabilization to propidium iodide and ATP efflux in response to C4. Unlike the antifungal peptide histatin 5, it did not require energy-dependent transport across the membrane. Rapid membrane disruption was observed by both fluorescence and electron microscopy. The compound was highly active in vitro against numerous fluconazole-resistant clinical isolates of C. albicans and non-albicans species, and it exhibited potent, dose-dependent activity in a mouse model of invasive candidiasis, reducing kidney burden by three logs after 24 hours, and preventing mortality for up to 17 days. Together the results support the development of this class of antifungal drug to treat invasive candidiasis.
Article 0 Reads 2 Citations Modulation of Human β-Defensin-1 Production by Viruses Lisa Kathleen Ryan, Gill Diamond Published: 21 June 2017
Viruses, doi: 10.3390/v9060153
DOI See at publisher website PubMed View at PubMed ABS Show/hide abstract
While initially identified as a broad-spectrum antimicrobial peptide, constitutively expressed in epithelia, human β-defensin (hBD)-1 is now recognized to have a more complex pattern of expression of its gene, DEFB1, as well as activities that extend beyond direct antimicrobial. These observations suggest a complex role for hBD-1 in the host defense against viral infections, as evidenced by its expression in cells involved in viral defense, and its gene regulation in response to viral challenge. This regulation is observed both in vitro and in vivo in humans, as well as with the murine homolog, mBD-1. While numerous reviews have summarized the existing literature on β-defensin gene expression and activity, here we provide a focused review of relevant studies on the virus-mediated regulation of hBD-1 and how this regulation can provide a crucial aspect of the innate immune defense against viral infection.
Conference papers
CONFERENCE-ARTICLE 18 Reads 0 Citations In vivo imaging of the activity of host defense peptide mimetics in a mouse model of invasive candidiasis Gill Diamond, Lisa Ryan, Rezwana Parveen, Amy Hise, Katie Fr... Published: 03 November 2018
doi: 10.3390/ecmc-4-05628
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Systemic fungal infections are increasingly common, especially in immune compromised patients. Even with newly developed drugs, there remain issues of limited spectrum, side effects, and the development of resistance. Host defense peptides (HDPs) have been examined recently for their utility as therapeutic antifungals, especially due to the low levels of resistance that develop. Unfortunately, the peptides exhibit poor pharmacologic properties in vivo. We have demonstrated the potent activity of nonpeptidic compounds that mimic HDPs in both structure and function against clinical strains of Candida albicans associated with oral and invasive candidiasis in mouse models. However, to test numerous compounds in vivo requires large numbers of mice, with multiple time points, and requires immunosuppression of the mice using cyclophosphamide, which can influence pharmacological parameters. We have identified a strain of mouse that develops invasive candidiasis without the need for immunosuppressive drugs. When we infect these mice with a strain of C. albicans that constitutively expresses Red Fluorescent Protein, we can quantify the infection in real time by in vivo imaging. We can further observe the reduction in fluorescence in infected mice after treatment with an HDP mimetic. Together our results demonstrate a novel in vivo method for screening new antifungal drugs.

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