Graduate students: Julia Sutter and Caroline Corcoran

Ongoing research efforts follow my interest in the highly translational field of plasma medicine, which encompasses the exploration of promising biomedical uses for nonthermal plasma (NTP). Our studies of NTP focus, in part, on dielectric barrier discharge plasma (DBDP), which is a form of NTP generated by applying high voltage to an electrode encased in a dielectric material. NTP has been proposed as the basis for a variety of translational applications, including cancer therapy and wound repair, and is already in clinical use in Europe. Strengths of NTP include:

• Ease of generation and delivery
• Controlled energy delivery by known and quantifiable mediators
• Limited and controllable cytotoxicity during delivery
• No residual cytotoxicity after delivery
• No known mechanisms of resistance to NTP

Figure credit: Truong et al., Apical Application of Nanosecond-Pulsed Dielectric Barrier Discharge Plasma Causes the Basolateral Release of Adenosine Triphosphate as a Damage-Associated Molecular Pattern from Polarized HaCaT Cells. Plasma Medicine, 2017. https://doi.org/10.1615/PlasmaMed.2017019120

Two lines of investigation are being followed in efforts to develop NTP-based preventative and therapeutic approaches applicable to virus infections. In the first, efforts have been committed to pursuing an NTP-based immunotherapy for people living with human immunodeficiency virus (HIV) infection. Initial in vitro studies, described in papers published in PLOS One (2021) and Biomedicines (2023), serve as the foundation for future pre-clinical and clinical studies. The second line of investigation focuses on the development of an NTP-based therapy for epithelial infections by the herpes simplex virus types 1 and 2 (HSV-1 and -2). The overall goal of this research is to leverage the antiviral and immunomodulatory effects of NTP application to create safe and effective therapies for oral and genital herpes.

Figure credit: Non-thermal Plasma Modulates Cellular Markers Associated with Immunogenicity in a Model of Latent HIV-1 Infection. International Low Temperature Plasma Community (ILTPC) Newsletter (No. 12, April 7, 2021) https://mipse.umich.edu/iltpc_newsletter12.php#research

These multi-disciplinary studies are being conducted in collaboration with Dr. Vandana Miller (also in the Department of Microbiology and Immunology) as well as investigators with complementary expertise at the North Carolina State University, Rutgers University, Princeton University and the University of Minnesota. Our collective studies have been supported by a number of agencies, including the National Institutes of Health, the Coulter-Drexel Translational Research Partnership Program, the Princeton Collaborative Low Temperature Plasma Research Facility, and the United States Department of Energy.

“Research Highlights and Breakthroughs: Biological Targets Alter Electrical Characteristics and Chemistry of Non-Thermal Plasma”
International Low Temperature Plasma Community (ILTPC) Newsletter. No. 36 (November 17, 2023)

“Research Highlights and Breakthroughs: Non-thermal Plasma Modulates Cellular Markers Associated with Immunogenicity in a Model of Latent HIV-1 Infection”
International Low Temperature Plasma Community (ILTPC) Newsletter. No. 12 (April 7, 2021)

“Research Highlights and Breakthroughs: Nonthermal plasma as Part of a Novel Strategy for Vaccination”
International Low Temperature Plasma Community (ILTPC) Newsletter. No. 5 (August 7, 2020)

"Infectious Disease Scientists in Demand"
College of Medicine Newsroom (February 16, 2015)

"Intricate Transmission"
Exel - Drexel University Research Magazine (2013)

Selected Publications
(See all Fred Krebs' publications in PubMed.)

“Manipulation of Oxidative Stress Responses by Non-Thermal Plasma to Treat Herpes Simplex Virus Type 1 Infection and Disease”
Sutter, J., Bruggeman, P.J., Wigdahl, B., Krebs, F.C., and Miller, V.
Int J Mol Sci 24. (2023)

“Inclusion of Biological Targets in the Analysis of Electrical Characteristics of Non-Thermal Plasma Discharge”
Sutter, J., Brettschneider, J., Mamchur, S., Krebs, F., Gershman, S., and Miller, V.
Plasma 6, 577-591 (2023)

“Immunomodulatory Effects of Non-Thermal Plasma in a Model for Latent HIV-1 Infection: Implications for an HIV-1-Specific Immunotherapy”
Mohamed, H., Berman, R., Connors, J., Haddad, E.K., Miller, V., Nonnemacher, M.R., Dampier, W., Wigdahl, B., and Krebs, F.C.
Biomedicines 11 (2023)

“Non-Thermal Plasma as a Novel Strategy for Treating or Preventing Viral Infection and Associated Disease”
Mohamed, H., Nayak, G., Rendine, N., Wigdahl, B., Krebs, F.C., Bruggeman, P.J., and Miller, V.
Frontiers in Physics 9 (2021)

“Differential Effect of Non-Thermal Plasma RONS on Two Human Leukemic Cell Populations”
Mohamed, H., Gebski, E., Reyes, R., Beane, S., Wigdahl, B., Krebs, F.C., Stapelmann, K., and Miller, V.
Cancers (Basel) 13 (2021)

“Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection”
Mohamed, H., Clemen, R., Freund, E., Lackmann, J.W., Wende, K., Connors, J., Haddad, E.K., Dampier, W., Wigdahl, B., Miller, V., Bekeschus, S., and Krebs, F.C.
PLoS One 16, e0247125 (2021)

“GSH Modification as a Marker for Plasma Source and Biological Response Comparison to Plasma Treatment”
Ranieri, P., Mohamed, H., Myers, B., Dobossy, L., Beyries, K., Trosan, D., Krebs, F.C., Miller, V., and Stapelmann, K.
Applied Sciences 10 (2020)

“The Evolution of Dendritic Cell Immunotherapy against HIV-1 Infection: Improvements and Outlook”
Mohamed, H., Miller, V., Jennings, S.R., Wigdahl, B., and Krebs, F.C.
J Immunol Res 2020, 9470102 (2020)

“Nonthermal plasma as part of a novel strategy for vaccination”
Mohamed, H., Esposito, R.A., Kutzler, M.A., Wigdahl, B., Krebs, F.C., and Miller, V.
Plasma Process Polym 17, 2000051 (2020)

“Non-Thermal Plasma-Induced Immunogenic Cell Death in Cancer: A Topical Review”
Khalili, M., Daniels, L., Lin, A., Krebs, F.C., Snook, A.E., Bekeschus, S., Bowne, W.B., and Miller, V.
J Phys D Appl Phys 52 (2019)

“Apical Application of “Nanosecond-pulsed dielectric barrier discharge plasma causes the basolateral release of adenosine triphosphate as a damage-associated molecular pattern from polarized HaCaT cells”
Truong B, K Siegert, A Lin, V Miller, and FC Krebs
Plasma Medicine, 7: 117-131, 2017

“Specific amino acids in HIV-1 Vpr are significantly associated with differences in patient neurocognitive status”
Dampier W, GC Antell, B Aiamkitsumrit, MR Nonnemacher, JM Jacobson, V Pirrone, W Zhong, K Kercher, S Passic, JW Williams, T James, KN Devlin, T Giovannetti, DJ Libon, Z Szep, GD Ehrlich, B Wigdahl, and FC Krebs
J Neurovirol, 23:113-124, 2017

“Evidence of divergent amino acid usage in comparative analyses of R5- and X4-associated HIV-1 Vpr sequences”
Antell GC, W Dampier, B Aiamkitsumrit, MR Nonnemacher, V Pirrone, W Zhong, K Kercher, S Passic, J Williams, Y Liu, T James, JM Jacobson, Z Szep, B Wigdahl, and FC Krebs
Int J Genomics, 2017:4081585, 2017

“Variability in human semen content and its potential effects in the female reproductive tract”
Keogan S, K Siegert, B Wigdahl, and FC Krebs
Journal of Reproductive Biology and Health, 4: 1, 2016

“Defining the roles for Vpr in HIV-1-associated neuropathogenesis”
James T, MR Nonnemacher, B Wigdahl, and FC Krebs
J Neurovirol, 22:403-415, 2016

“cAMP signaling enhances HIV-1 long terminal repeat (LTR)-directed transcription and viral replication in bone marrow progenitor cells”
Banerjee A, L Li, V Pirrone, FC Krebs, B Wigdahl, and MR Nonnemacher
Clin Med Insights Pathol,10: 1179555717694535, 2016

“Utilization of HIV-1 envelope V3 to identify X4- and R5-specific Tat and LTR sequence signatures”
Antell GC, W Dampier, B Aiamkitsumrit, MR Nonnemacher, JM Jacobson, V Pirrone, W Zhong, K Kercher, S Passic, JW Williams, G Schwartz, U Hershberg, FC Krebs, and B Wigdahl
Retrovirology, 13: 32, 2016

“Critical Review: Immunomodulation by seminal factors and implications for male-to-female HIV-1 transmission
Keogan S, K Siegert, B Wigdahl, and FC Krebs
J Acquir Immune Defic Syndr, 69:131-137, 2015