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Katie Freeman   Dr.  Senior Scientist or Principal Investigator 
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Katie Freeman published an article in February 2018.
Top co-authors See all
Gill Diamond

14 shared publications

Department of Oral Biology, Rutgers New Jersey Dental School, Newark, NJ 07103, USA

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

Damian G. Weaver

1 shared publications

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

2
Publications
19
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11
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0
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Publication Record
Distribution of Articles published per year 
(2018)
Total number of journals
published in
 
1
 
Publications
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.
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
DOI See at publisher website ABS Show/hide abstract

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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