• International Society for Plasma Medicine
• International Society of Plasma Chemistry
• International Society for Plasmas in Cancer

Postdoctoral fellow: Dr. Hager Mohamed

Graduate Student: Julia Sutter

Undergraduate students: 3-4 co-operative learning students and 1-2 biology research students each year

RESEARCH INTERESTS

Dr. Miller’s main interest is in the development of non-thermal plasmas for modulation of immune function in the management of precancerous skin lesions, cancers, infectious diseases and in wound healing. Her laboratory works towards developing the understanding of basic interactions between plasma components and live cells/tissues as well as the more translation aspects of device development for clinical use.

Plasma medicine is an emerging experimental therapeutic field that employs the use of non-thermal plasma (NTP), a partially ionized gas, for controlled manipulation of cellular redox. Dr. Miller’s research focus is on the in vitro and in vivo immunomodulatory effects of non-thermal plasma for applications in immunotherapy of cancer, viral diseases and wound healing. She works closely with tumor immunologists, surgeons, dermatologists, virologists, immunologists, and collaborates with plasma scientists (engineers, chemists, computational scientists and physicists) in USA, Germany, Italy, Spain, South Korea, Belgium and Japan. She was the first to demonstrate that NTP directly alters the functional profile of antigen presenting cells in vitro and in vivo. She was also the first to establish that NTP is a bona fide inducer of immunogenic cell death in cancer cells which resulted in development of tumor specific CD8+ T cells. She was part of the research team that conducted the first clinical trial for palliation in advanced head and neck cancers in Germany. Two successful clinical trials were conducted based on her work in the United States for actinic keratosis and therapy recalcitrant warts. These applications are being patented and in process for commercialization. She serves as the scientific advisor for a biomedical device company developing a plasma delivery system for treatment of dermatological diseases and a clinical prototype will soon be submitted for regulatory clearance.

Plasma Medicine is an Interdisciplinary Science

Antiviral effects of NTP: The direct effect of NTP on cell-free viruses is well documented in literature. A more thorough understanding of the antiviral properties and safety of NTP has stimulated explorations of NTP as the basis for treatments of viral diseases. The recently described immunomodulatory properties of NTP are also being evaluated for potential use in immunotherapies of viral diseases. In vitro, ex vivo and in vivo approaches are being used to define the active pathways triggered by NTP in the treatment of herpes simplex lesions and as an immunotherapeutic cure strategy for latent HIV infections.

Source: Khalili M, Daniels L, Lin A, Krebs FC, Snook AE, Bekeschus S, Bowne WB, Miller V. Non-Thermal Plasma-Induced Immunogenic Cell Death in Cancer: A Topical Review. J Phys D Appl Phys. 2019 Oct 22;52(42):423001. doi: 10.1088/1361-6463/ab31c1. Epub 2019 Aug 6. PMID: 31485083; PMCID: PMC6726388.

Immunological Control of Cancers through NTP Induced Immunogenic Cell Death: Exploration of the anti-cancer capacity of NTP remains a main focus of her ongoing research efforts. Immunogenic cell death (ICD) is an atypical cell death pathway whereby cells emit Damage Associated Molecular Patterns (DAMPs) – ATP, ecto-Calreticulin (CRT), HSP90, HMGB1 etc.- that serve to recruit immune cells into the tumor and initiate pathways of immunological control of the tumor. Guido Kramer’s group has categorically demonstrated that ecto-CRT serves as an “eat me” signal for neutrophils and macrophages and stimulates protective anti-cancer immune responses. Dr. Miller’s laboratory has demonstrated that NTP induces this pathway in several different tumor cell lines – colorectal (CT26), lung (A549), as well as some radiation and multi-drug resistant cell lines like nasopharyngeal (CNE1) and pancreatic adenocarcinoma (Panc02). The work also shows that emitted DAMPs stimulate macrophage anti-tumor functions in vitro and in vivo. Collaborative studies (TJU) in a murine model of colorectal carcinoma were the first to provide in vivo evidence of NTP-mediated ICD which was accompanied with intra-tumoral recruitment of neutrophils and dendritic cells and was followed by development of tumor specific CD8+ splenic T cells. Partial protection by vaccination with tumor cells undergoing NTP-triggered ICD was also demonstrated.

Mechanism of Action and Selectivity of NTP: NTP-generated reactive oxygen species (ROS) have been demonstrated to be the major influencers of cell death. Since NTP works through induction of oxidative stress pathways, it is important that the effects be targeted selectively at diseased cells and tissues. Plasma effects can be made selective either through interaction with immune cells or through control of plasma delivered species. Part of her efforts are focused on on identifying the key NTP effectors that influence other cellular functions and processes through collaborative studies with Dr. Katharina Stapelmann (North Carolina State University). This NIH-funded (1R01EB029705-01A1) work employs the use of engineered physico-chemical barriers and chemical ROS scavengers along with comparative analysis between different plasma devices each producing a different cocktail of ROS. The collaboration is also working on real-time detection of plasma effects and integrating it into biological readouts through deep machine learning to develop a feedback system that would allow for controlled delivery of NTP. This is a challenge in the plasma medicine community because no cause-effect relationship has yet been established between biological outcomes and specific NTP components.

We are also investigating the influence of biological substrates on dielectric barrier discharge composition in collaboration with Dr. Sophia Gershman at the Princeton Plasma Physics Laboratory. This work is funded by the Plasma Research Facility at Princeton which has state-of-the art plasma diagnostic capabilities.

Effects of NTP on normal and diseased skin/keratinocytes: Treatment of dermatological diseases is the target of Plasmend, a start-up NTP device manufacturing company. Through projects funded by the company the laboratory works to establish the fundamentals of NTP application to skin for acne, actinic keratoses, warts, different skin cancers and for skin rejuvenation.

Patent Applications

Co-Inventor - 2016. Device and Methods for Treatment of Skin Diseases. International Publication Number: WO2018/026750A1. February 2018.

Co-Inventor - 2016. Methods of Generation of Planar Plasma Jets. International Publication Number: PCT/US2019/18689. August 2019. (Approved Sep 2021)

Meet the Expert Interview

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Book Chapters

"Cancer Immunology"
Sander Bekeschus, Alexander Fridman, Vandana Miller
in Comprehensive Clinical Plasma Medicine, Published by Springer Nature (2017)

"Immunology in Plasma Cancer Treatment"
Sander Bekeschus, Georg Bauer, Vandana Miller
in Plasma Cancer Treatment, published by Springer (2020)

Selected Publications

"Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection"
Mohamed, Hager, Clemen, Ramona, Freund, Eric, Lackmann, Jan-Wilm, Wende, Kristian, Connors, Jennifer, Haddad, Elias K., Dampier, Will, Wigdahl, Brian, Miller, Vandana, Bekeschus, Sander, Krebs, Fred C.
PLOS ONE 16(3): e0247125 (2021)

"Non-thermal plasma as a novel strategy for treating or preventing viral infection and associated disease"
Hager Mohamed, Gaurav Nayak, Nicole Rendine, Brian Wigdahl, Fred C. Krebs, Peter Bruggeman, and Vandana Miller¹
Frontiers in Physics March 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.; Miller, V.
Cancers (2021)

"Low Temperature Plasma for Biology, Hygiene, and Medicine: Perspective and Roadmap"
Laroussi, Mounir; Bekeschus, Sander; Bogaerts, Annemie; Fridman, Alexander; Lu, Xinpei; Miller, Vandana; et al.
TechRxiv. Preprint (2021)

"GSH Modification as a Marker for Plasma Source and Biological Response Comparison to Plasma Treatment"
Pietro Ranieri, Hager Mohamed, Brayden Myers, Leah Dobossy, Keely Beyries, Duncan Trosan, Fred C. Krebs, Vandana Miller and Katharina Stapelmann
Appl. Sci., 10, 2025 (2020)

"The Evolution of Dendritic Cell Immunotherapy against HIV-1 Infection: Improvements and Outlook"
Hager Mohamed, Vandana Miller, Stephen R. Jennings, Brian Wigdahl, and Fred C. Krebs
Journal of Immunology Research, vol. 2020, Article ID 9470102 (2020)

Effects of cold physical plasma on oral lichen planus: An in vitro study (Effects of CAP on OLP)
Seebauer C, Freund E, Hasse S, Miller V, Segebarth M, Lucas C, Kindler S, Dieke T, Metelmann HR, Daeschlein G, Jesse K, Weltmann KD, Bekeschus S
Oral Dis. (October 27, 2020)

Non-thermal plasma as part of a novel strategy for vaccination
Hager Mohamed, Rita A. Esposito, Michele A. Kutzler, Brian Wigdahl, Fred C. Krebs, Vandana Miller
Plasma Processes and Polymers, 17:e2000051 (2020)

Activity of murine splenocytes upon co-culture with plasma treated B16F10 melanoma cells
Katrin Rödder, Juliane Moritz, Vandana Miller, Klaus-Dieter Weltmann, Hans-Robert Metelmann, Rajesh Gandhirajan, Sander Bekeschus
Appl. Sci., 9(4), 660 (2019)

Non-Thermal Plasma-Induced Immunogenic Cell Death in Cancer: A Topical Review
Marian Khalili, Lynsey Daniels, Abraham Lin, Fred C. Krebs, Adam E. Snook, Sander Bekeschus, Wilbur B. Bowne, Vandana Miller
Journal of Physics D: Applied Physics, Volume 52, Number 42 (2019)

"Plasma Onco-Immunotherapy: the future of cancer treatment?"
Plenary speaker 6th International Conference on Plasma Medicine, Bratislava, Slovakia (September 2016)

"Plasma Immunotherapy of Cancer"
Gordon Research Conference, Andover, N.H. (July 2016)

"Nanosecond-pulsed DBD plasma for a clinical trial of Actinic Keratosis"
International Workshop on Plasmas in Cancer, Greifswald, Germany (March 2018)

"Plasma Immunotherapy of Cancers"
American Vacuum Society, Long Beach, Calif. (October 2018)

"Cold Plasma in Dermatology"
Fall Dermatology Meeting, New York, N.Y. (October 2019)

"Plasma and the Immune System"
Low Temperature Plasma International Online Seminars (July 2020)