EPIC: At the forefront of biomedical research on eukaryotic pathogens

EPIC: At the forefront of biomedical research on eukaryotic pathogens

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Eukaryotic pathogens cause some of the most devastating and intractable diseases in humans, including malaria, amoebic dysentery, sleeping sickness, Chagas disease and fungal meningitis. Globalization has increased such infections in the U.S. Many eukaryotic pathogens are classified as bioterrorism agents and/or neglected tropical diseases.

Clemson University’s Eukaryotic Pathogens Innovation Center — EPIC — is an interdisciplinary research cooperative founded in 2013 that is at the forefront of biomedical research on these devastating pathogens.

EPIC scientists have a lengthy track record of major contributions in this globally important area of research.

EPIC News Bites

EPIC Logo in Black

EPIC and The Department of Biological Sciences are Hiring!

The Department of Biological Sciences at Clemson University and the Eukaryotic Pathogens Innovation Center (EPIC) invite applications for a tenure-track ASSISTANT PROFESSOR position, to be filled by an innovative scholar whose research is in an area that complements our current department and center strengths. The anticipated start-date is August 2025.

We seek a candidate who will build a research program centered on parasitic and/or fungal diseases, including, but not limited to, mechanistic aspects of pathogen biology, pathogen-host or pathogen-vector interactions, evolution and ecology of infectious disease, drug-delivery, or translational research on communicable diseases caused by eukaryotic pathogens. Applicants who leverage cutting-edge techniques to address questions about host immunity are highly encouraged to apply. Click here for more information and to apply.

Two people looking at a poster at the REDDI Lab Research Symposium

EPIC Students Present at REDDI Lab Symposium

Dylan Carroll, a genetics major in the Smith lab, and Sabrina Sutton Pizarro, a PhD student in Jim Morris lab, presented their research at the 4th Annual REDDI Lab Research Symposium entitled ‘Broadening Research at Professional Development in Clinical Diagnostics and Healthcare’ at the Hyatt Regency in Greenville, SC on Friday September 13th. Dylan’s poster was entitled “Carnitine Biosynthesis in Cryptococcus neoformans” and Sabrina’s poster was entitled “Exploration of Putative Sodium/Proton Exchangers in Trypanosoma brucei.”

zebra fish swimming

EPIC Researchers Uncover How Glucocorticoids Increase Susceptibility to Fungal Infections

EPIC researchers Dr. Savini Thrikawala, Molly Anderson, and Dr. Emily Rosowski, have published a new study in The Journal of Immunology titled “Glucocorticoids Suppress NF-κB–Mediated Neutrophil Control of Aspergillus fumigatus Hyphal Growth.” The study explores how glucocorticoids, commonly used anti-inflammatory drugs, increase vulnerability to infections caused by the fungus Aspergillus fumigatus. Using a zebrafish model, the researchers discovered that these drugs suppress NF-κB–mediated neutrophil responses, leading to enhanced fungal growth and increased mortality. This research provides crucial insights into the immunosuppressive effects of glucocorticoids and their role in heightening the risk of opportunistic infections.

 Stephani Martinez Barerra

Congratulations to Stephani Martinez Barerra on earning her PhD and Several Awards

Stephani Martinez Barrera recently earned her PhD and was recognized with several prestigious awards. She received the Department of Genetics & Biochemistry’s Outstanding Graduate in Learning (BIMB) Award for her exceptional work as a Graduate Teaching Assistant. Stephani was also honored with Clemson University’s Interdisciplinary Research Endowed Fellowship for her contributions to research and teaching in the Department of Genetics & Biochemistry, and the Spring 2024 NSF Rising Scientist Award.

 Dan Whitehead and Alexis Stamatikos

Congratulations to Drs. Dan Whitehead and Alexis Stamatikos on Their Successes in Acquiring NIH Awards

Dr. Whitehead was awarded a NIH R35 MIRA grant (R35GM153221) to develop rare heterocyles to understand pathogen metabolism, while Dr. Stamatikos was awarded a NIH R01 (R01HL175166) to identify novel atheroprotective mechanisms. Both were Research Project Leaders on the Phase 2 EPIC COBRE, and we look forward to their future successes. Congratulations Dan and Alexis!

 PA4170 is the most highly differentially expressed P. aeruginosa gene during coculture with A. fumigatus in SCFM2, and expression is activated upon gliotoxin exposure. (A) Schematic illustrating the A. fumigatus and P. aeruginosa coculture setup. A. fumigatus is first inoculated into SCFM2 to facilitate germination and hyphal development, followed by P. aeruginosa inoculation. Coculture was imaged by confocal laser scanning microscopy (CLSM) at 18 h, 37 °C. A. fumigatus was labeled with constitutively expressed mNeonGreen, and P. aeruginosa with mCherry. The data are representative of three independent experiments, each performed in triplicate. (Scale bar, 20 µm.) (B) Volcano plot illustrating P. aeruginosa genes differentially expressed upon coculture with A. fumigatus. Bubble colors are used to indicate genes significantly altered in expression with a log2 fold change greater than 1 (blue), less than −1 (green), above the adjusted P-value threshold (orange), or unchanged (black). Significantly altered clusters of genes (>5) with established functions in P. aeruginosa are shown (zinc acquisition, iron acquisition, denitrification, and copper homeostasis). PA4170 (dotted box) was the highest differentially expressed gene (93.7-fold-change). The experiment was performed using biological triplicates. (C) mCherry-tagged PA4170 reporter assay examining PA4170 expression following P. aeruginosa growth in spent A. fumigatus SCFM culture supernatants (24 h) supplemented with different metals (5 µM FeSO4, ZnSO4, CuSO4, and MnSO4). Fluorescence was read at 6 h and normalized to cell density (OD600). The data are representative of three independent experiments performed in triplicate. Statistical significance was calculated by one-way ANOVA with Dunnett’s multiple comparisons test using “SCFM Af” as the control column (****P < 0.0001). Error bars represent SD from the mean. (D) Untargeted metabolomics of A. fumigatus culture supernatants during growth in SCFM and SCFM + 10 µM ZnSO4 (24 h) identified gliotoxin as significantly lowered upon zinc supplementation. Chromatograms show the peak corresponding to gliotoxin (triplicate), alongside a commercial standard. The experiment was performed using biological triplicates. (E) mCherry-tagged PA4170 reporter fluorescence assay examining PA4170 protein expression in SCFM following gliotoxin (GT) or bisthiomethylgliotoxin (bmGT) supplementation (0 to 60 µM). Fluorescence was read at 8 h and normalized to cell density (OD600). The data are representative of two independent experiments performed in triplicate. Statistical significance was calculated by one-way ANOVA with Dunnett’s multiple comparisons test using “0 µM GT” as the control column (*P = 0.0197 and ****P < 0.0001). Error bars represent SD from the mean.

Convergent evolution in toxin detection and resistance provides evidence for conserved bacterial–fungal interactions

Stephen Dolan’s latest research, published in PNAS, sheds light on the complex interactions within polymicrobial communities. The study reveals how the human pathogen Pseudomonas aeruginosa has developed a genetic network to detect and neutralize gliotoxin, a potent antimicrobial produced by the fungus Aspergillus fumigatus. Dolan’s findings highlight a fascinating example of convergent evolution, where both the bacterium and fungus have evolved similar mechanisms for toxin resistance despite their evolutionary differences. This discovery enhances our understanding of microbial interactions and could inform future treatments for infections involving P. aeruginosa. Read the article.

 The active site of NfENO (PDB 7UGH, grey) overlayed on the human HEX-bound ENO structure (PDB 5IDZ, pink), showing that all residues of the binding pocket are conserved with the sole exception of Lys243, which corresponds to Ser157 in the human enzyme (all other residue numberings refer to NfENO). Carbon atoms of the NfENO 2-phosphoglyceric acid ligand are colored green, while those of HEX are shown in black. The phosphate groups of the two ligands overlap and are both positioned close to NfENO Lys243; the yellow dotted line shows the closest interatomic distance between the Lys243 amine group and the HEX phosphate.

Enolase inhibitors as therapeutic leads for Naegleria fowleri infection

A team of researchers, including Jillian Milanes, Samuel Kwain, Dan Whitehead, and Jim Morris, have published a groundbreaking study in PLOS Pathogens titled “Enolase inhibitors as therapeutic leads for Naegleria fowleri infection.” The study explores the potential of enolase inhibitors, originally developed for treating glioblastoma, as a new approach to combat the life-threatening brain infection caused by the amoeba Naegleria fowleri. Their findings suggest that the inhibitor HEX shows promise in extending survival in animal models, marking a significant step forward in the search for effective treatments against this often fatal condition. Read the article.

NISBRE Logo

Students Presenting at 9th Annual NISBRE Conference

Four EPIC graduate students are excited to attend the 9th Biennial National IDeA Symposium of Biomedical Research Excellence (NISBRE) at the Washington Hilton on June 16-19. The NISBRE conference showcases the accomplishments of the IDeA program, which supports scientific centers of excellence and trains biomedical scientists in IDeA-eligible states. Attendees will have the opportunity to listen to high-level scientific presentations and to participate in poster sessions, discussion forums, and workshops designed to develop new scientific and career skills. This event provides an excellent opportunity for networking, collaboration, and interaction with NIH staff. The following students will be presenting:
Victoria Murphey: Assessing an actin binding protein, thymosin beta-4, as a novel treatment for Acanthamoeba keratitis
Claudia Gonzalez: Investigating Initiation of Encystation in The Intestinal Parasite Entamoeba histolytica
Arohi Singhal: Unravelling Cryptococcus neoformans Metabolic Adaptations: Implications for Therapeutic Targets
Jack Talledo: Investigating the role of chitin synthases 1 and 2 in encystation in the human pathogen Entamoeba histolytica

EPIC, Seifert Scholars, and MEnTOR logos

Exciting New Additions to Our Labs This Summer

We are thrilled to announce the arrival of new students joining the Eukaryotic Pathogens Innovation Center (EPIC) research labs this summer through two prestigious programs: the Seifert Scholars and MEnTOR.

The Seifert Scholars program will welcome seven new students who will contribute to our ongoing research projects. These talented individuals will not only enhance our summer initiatives but will also continue their work with us through the Fall and Spring semesters, ensuring a continuous and impactful presence in our labs.

Additionally, MEnTOR will host three new students this summer. These students come to us from the University of South Carolina School of Medicine in Greenville and are set to make significant contributions to our research endeavors during their time with us.

We are excited about the fresh perspectives and innovative ideas that these students will bring to our research community. Their involvement will undoubtedly enrich our programs and drive forward EPIC’s mission of scientific discovery and excellence

Dr. Manuel Fierro

EPIC Welcomes New Faculty Member

We are excited to welcome Dr. Manuel Fierro to EPIC. Dr. Fierro, currently a post-doctoral researcher with Dr. Josh Beck in the Roy J. Carver Department of Biochemistry, Biophysics, and Molecular Biology at Iowa State University, will be joining the Department of Genetics and Biochemistry as an assistant professor. His research has been focused on characterizing the essential protein trafficking machinery in Plasmodium, a genus of parasites that cause malaria in humans. His innovative molecular tools are opening new avenues for understanding the intricate mechanisms behind protein export recognition in eukaryotic pathogens.
We look forward to Dr. Fierro joining us next October.

Questions?

For further information about the EPIC please contact us.

864-656-EPIC or clemson_epic@clemson.edu