91制片厂

• International Society for Plasma Medicine
• International Society of Plasma Chemistry
• Chair, International Workshop on Plasmas for Cancer Treatment

Plasma medicine is an emerging experimental therapeutic field that employs the use of non-thermal plasma (NTP), for controlled manipulation of cellular redox. My research focus is on the in vitro and in vivo immunomodulatory effects of NTP for applications in immunotherapy of cancer, viral diseases and wound healing. I work closely with oncologists, 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. My research was the first to demonstrate that NTP directly alters the functional profile of antigen presenting cells in vitro and in vivo. I 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. I 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 my work in the United States for actinic keratosis and therapy recalcitrant warts.

The following projects are active in the lab:

Mechanism of action and selectivity of NTP using a wound healing model

Funded by NIH R01EB029705

The overarching goal of this project is the development of a biosensor-based feedback control system based on real-time in situ measurement of NTP effectors, i.e., the control system will shut off NTP delivery upon real-time detection of markers indicative of a desired biological endpoint. Defining mechanism of action is a challenge in the plasma medicine community because no cause-effect relationship has yet been established between biological outcomes and specific NTP components. NTP-generated reactive oxygen species (ROS) are identified as the major influencers of cell death. This project focuses on identifying the key NTP effectors that influence cellular functions and processes in collaborative studies with Dr. Katharina Stapelmann (North Carolina State University). This 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. Translational feasibility is being tested in collaboration with Dr. Francois Berthiaume (Rutgers University) in a mouse model of acute wound healing. 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.

Influence of biological substrates on dielectric barrier discharge composition

Funded by the Department of Energy (DOE DE-SC0024539) and the Princeton Collaborative Research Facility

The objective of this project is to investigate the dynamic interactions between non-thermal plasma (NTP) and biological targets suspended in their physiological liquid medium. We will examine how cell behavior is altered by NTP through chemical and ionic changes produced in liquids surrounding them and in turn, how the changing biological target affects plasma properties. Our recent correlative work with Dr. Sophia Gershman at the Princeton Plasma Physics Laboratory suggests that cells and the surrounding medium can change the composition of NTP cocktail. Thus, the interactions between NTP and cells evolve in real time and continue to alter each other. Better understanding of these reciprocal interactions is needed to develop safe therapeutic applications of NTP for different diseases.

This project correlates experimental observations performed in our laboratories at 91制片厂 with principles of biophysics for an in-depth analysis of the dominant mechanisms that influence cell fate when they are exposed to NTP. Prof. Mikhail Schneider, a computational and theoretical physicist at Princeton University will develop quantitative theory to explain and predict the NTP induced changes the ion composition in solutions exposed to NTP, leading to a change in osmotic pressure, and its possible effects on the cell morphology, the cell shape, and cell viability. Dr. Sophia Gershman at the Princeton Plasma Physics Laboratory which has state-of-the art plasma diagnostic capabilities will address the crucial questions of the feedback between biological substrates and plasma conditions in the direct plasma treatment of cells.

Antiviral effects of NTP

Funded by the Coulter-Drexel Translational Research Partnership Program (oral Herpes Simplex Virus Type 1 infections) and the Comprehensive NeuroHIV Center Pilot Program (NTP-based immunotherapy for HIV-1 infection)

The direct effect of NTP on cell-free viruses is well documented in literature. As more thorough understanding of the antiviral properties and safety of NTP develops, it 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 oral herpes simplex lesions (in collaboration with Dr. Brian Wigdahl, Dr. Fred Krebs and Dr. Stephen Jennings) and as an immunotherapeutic cure strategy for latent HIV infections (in collaboration with Dr. Brian Wigdahl, Dr. Fred Krebs, Dr. Jacquelin Barker, Dr. Gabriel Romano and Dr. Mike Nonnemacher).

Immunological Control of Cancers through NTP Induced Immunogenic Cell Death

Exploration of the anti-cancer capacity of NTP remains a focus of my ongoing research efforts. Immunogenic cell death (ICD) is an atypical cell death pathway whereby cells emit Damage Associated Molecular Patterns (DAMPs) 鈥� 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鈥檚 group has categorically demonstrated that ecto-CRT serves as an 鈥渆at me鈥� signal for neutrophils and macrophages and stimulates protective anti-cancer immune responses. My laboratory has demonstrated that NTP induces this pathway in several different tumor cell lines 鈥� 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. We continue these explorations in collaboration with Dr. Hartsough (melanoma) and for pancreatic cancer with Drs. Bowne (Thomas Jefferson) and Campbell (Fox Chase Cancer Center).

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.

Effects of NTP on biofilms

This new project capitalizes on Dr. Donald Hall鈥檚 expertise in treatment of persistent biofilms.

Patent Applications

Patents

Method of generation of planar plasma jets, Danil V. Dobrynin, Alexander Fridman, Abraham Lin, Vandana Miller, Adam Snook; Patent number: 11219118; Filed: February 20, 2019; Date of Patent: January 4, 2022

Patent Applications

• Method Of Vaccination Against Cancer Using Plasma Treated Cancer Cells, Danil V. Dobrynin, Alexander Fridman, Abraham Lin, Vandana Miller, Adam Snook; Filed: January 3, 2022; Publication date: August 11, 2022, Publication number: 20220256682
• Device and Methods for Treatment of Skin Diseases, Peter C. FRIEDMAN, Vandana MILLER, Gregory FRIDMAN, Abraham LIN, Alexander FRIDMAN; Filed: August 1, 2017; Publication date: September 16, 2021; Publication number: 20210282831
• Use of Cold Atmospheric Pressure Plasma to Treat Warts, Peter C. Friedman, Vandana Miller, Gregory Fridman, Abraham Lin, Alexander Fridman; Filed: June 26, 2019; Publication date: August 26, 2021; Publication number: 20210260395

 
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Book Chapters

鈥淧lasma-induced immunogenic cancer cell death鈥�
Vandana Miller & Sander Bekeschus
In Redox Biology in Plasma Medicine, CRC Press (Taylor & Francis Group), Edited by Sander Bekeshcus and Thomas von Woedtke, Anticipated release date: December 2023

鈥淗ow to Assure Good Clinical Practice in Plasma Therapy?鈥�
Hans-Robert Metelmann, Stefan Hammes, Kristina Hartwig, Christian Seebauer, Ajay Rana, Eun Ha Choi, Masaru Hori, Hiromasa Tanaka, Oksana Wladimirova, Vu Thi Thom, Vandana Miller, Anne Kirschner, Stefanie Kirschner & Thomas von Woedtke
In Textbook of Good Clinical Practice in Cold Plasma Therapy, published by Springer (2022)

鈥淐ancer Immunology鈥�
Sander Bekeschus, Alexander Fridman, Vandana Miller
In Comprehensive Clinical Plasma Medicine, Published by Springer Nature (2017)

鈥淚mmunology in Plasma Cancer Treatment鈥�
Sander Bekeschus, Georg Bauer, Vandana Miller
In Plasma Cancer Treatment, published by Springer (2020)

Selected Publications

Julia Sutter, Jascha Brettschneider, Sara Mamchur, Fred Krebs, Sophia Gershman, Vandana Miller
Plasma, 6(3), 577-591; (2023)

Julia Sutter, Brian Wigdahl, Fred C. Krebs, Vandana Miller
International Journal of Molecular Sciences, PMID: 36902102, PMCID: PMC10003306, DOI: 10.3390/ijms24054673 (Feb 24, 2023)

L Miebach, H Mohamed, K Wende, V Miller, S Bekeschus
Cancers (Basel). Jan 3;15(1):319. PMID: 36612315, PMCID: PMC9818580, DOI: 10.3390/cancers15010319 (2023)

Hager Mohamed, Rachel Berman, Jennifer Connors, Elias K. Haddad, Vandana Miller, Michael R. Nonnemacher, Will Dampier, Brian Wigdahl, Fred C. Krebs
Biomedicines, 11, 122. PMID: 36672628, PMCID: PMC9856147, DOI: 10.3390/biomedicines11010122 (2023)

Ajinkya Trimukhe, K. N. Pandiyaraj, Mukesh Patekar, Vandana Miller, R. R. Deshmukh
IEEE Transactions on Plasma Science, June, DOI: 10.1109/TPS.2022.3182717 (2022)

I. Adamovich, S. Agarwal, E. Ahedo, L.L. Alves, S. Baalrud, N. Babaeva, A. Bogaerts, A. Bourdon, P. J. Bruggeman, C. Canal, E.-H. Choi, S. Coulombe, Z. Donko, D. B. Graves, S. Hamaguchi, D. Hegemann, M. Hori, H.-H. Kim, G.M.W. Kroesen, M. J. Kushner , A. Laricchiuta, X. Li, T. Magin, S. Mededovic Thagard, V. Miller, A. B. Murphy, G. S. Oehrlein, N. Puac, R. M. Sankaran, S. Samukawa, M. Shiratani, M. Simek, N. Tarasenko, K. Terashima, E. Thomas Jr, J. Trieschmann, S. Tsikata, M. M. Turner, I. J. van der Walt, M. C. M. van de Sanden, T. von Woedtke
Journal of Physics D: Applied Physics, Volume 55, Number 37. (2022)

Mounir Laroussi, Sander Bekeschus, Michael Keidar, Annemie Bogaerts, Alexander Fridman, Xinpei Lu, Kostya Ostrikov, Masaru Hori,Katharina Stapelmann, Vandana Miller, Stephan Reuter, Christophe Laux, Ali Mesbah, James Walsh, Chunqi Jiang, Selma Mededovic Thagard, Hiromasa Tanaka, Dawei Liu, Dayun Yan, Maksudbek Yusupov
IEEE Transactions on Radiation and Plasma Medical Sciences, vol. 6, no. 2, pp. 127-157, Feb.,DOI: 10.1109/TRPMS.2021.3135118 (2022)

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)

Hager Mohamed, Gaurav Nayak, Nicole Rendine, Brian Wigdahl, Fred C. Krebs, Peter Bruggeman, and Vandana Miller¹
Frontiers in Physics March 2021)

Mohamed, H.; Gebski, E.; Reyes, R.; Beane, S.; Wigdahl, B.; Krebs, F.C.; Stapelmann, K.; Miller, V.
Cancers (2021)

Laroussi, Mounir; Bekeschus, Sander; Bogaerts, Annemie; Fridman, Alexander; Lu, Xinpei; Miller, Vandana; et al.
TechRxiv. Preprint (2021)

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)

Hager Mohamed, Vandana Miller, Stephen R. Jennings, Brian Wigdahl, and Fred C. Krebs
Journal of Immunology Research, vol. 2020, Article ID 9470102 (2020)

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)

Hager Mohamed, Rita A. Esposito, Michele A. Kutzler, Brian Wigdahl, Fred C. Krebs, Vandana Miller
Plasma Processes and Polymers, 17:e2000051 (2020)

Katrin R枚dder, Juliane Moritz, Vandana Miller, Klaus-Dieter Weltmann, Hans-Robert Metelmann, Rajesh Gandhirajan, Sander Bekeschus
Appl. Sci., 9(4), 660 (2019)

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)

鈥淧lasma Dose for Clinical Applications: New Considerations鈥�
International Symposium on Plasma Chemistry, Kyoto, Japan (May 2023)

鈥淐onsiderations for non-thermal plasma for inclusion as a therapeutic for patients with bacterial and viral infections鈥�
COST Actions, Bari, Italy (February 2023)

鈥淣on-thermal plasma - an emerging player in cancer immunotherapy鈥�
Pancreas Research Meeting, Thomas Jefferson University (April 2022)

鈥淧lasma Oncology, A Review鈥�
GEC International Online Plasma Seminar and Online Low Temperature Plasma Seminar (March 2022)

鈥淣on-thermal plasma 鈥� an emerging player in cancer therapy鈥�
Advanced Strategies for Radiotherapy: from the lab bench to medical applications, University Paris-Sarclay鈥檚 iNanoTheRad international meeting (Nov 2021)

鈥淣on-thermal plasma induced immunomodulation and its role in treatment of HIV-1 infection鈥�
International Conference on Advances in Plasma Science and Technology, Virtual, (May 2021)

鈥淧lasma and the Immune System鈥�
Low Temperature Plasma International Online Seminars (July 2020)

鈥淐old Plasma in Dermatology鈥�
Fall Dermatology Meeting, New York, N.Y. (October 2019)

鈥淧lasma Immunotherapy of Cancers鈥�
American Vacuum Society, Long Beach, Calif. (October 2018)

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

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

鈥淧lasma Immunotherapy of Cancer鈥�
Gordon Research Conference, Andover, N.H. (July 2016)