Cancer Biology & Treatment

在生物电子学中心，我们正在将非常高的电场——每米百万伏特——应用于生物医学目标，时间非常短——纳秒. These electric fields are stronger and shorter than had ever been used in the biology lab or the clinic... or in nature. Since cells and organisms have never in the history of life on earth seen this kind of electrical excitation, they have evolved no specific defense, regulatory, or signaling mechanisms that might be induced by this new kind of stimulation.

After initial nanosecond pulsed electric fields (nsPEF) experiments demonstrated success at decontaminating bacteria, researchers at the Center turned their attention to cancer. At that time, apoptosis was a central topic in cell and cancer biology research. Apoptosis is a programmed cell death, in contrast with unprogrammed necrosis, now called accidental death. The first studies to show that nanosecond pulses induce apoptosis, reduce mouse tumor size, and kill human tumor cells were in 2002 and 2003. Since then, ODU的研究表明，纳秒脉冲可以杀死多种类型的肿瘤，而且可以在治疗的动物中引起免疫反应. Ablation with nsPEF of melanoma, breast, liver, 结直肠癌会引发一种抗肿瘤免疫反应，既有助于肿瘤的根除，又能防止新肿瘤的形成. 该中心的研究人员目前正在描述这种免疫反应，并探索联合治疗的疗效.

Cold atmospheric plasma (CAP) produces reactive oxygen and nitrogen species, ions, and transient electric field, each exhibiting anticancer activity and together amplifying their individual activities to devastate malignant cells. 其作为一种抗癌疗法的可行性是由最近的临床试验CAP治疗头颈癌患者说明. At the Center for Bioelectrics, we focus on inhibitory effects of CAP on cancer metabolism, proliferative signaling, and inflammation and how they may be exploited to address therapy resistance. For example, 我们最近发现，在一个意想不到的低剂量方案下，CAP可以同时抑制癌症生存的多条供应线.g. metabolism, proliferative signaling, angiogenesis), often known as cancer hallmarks, in therapy-resistant malignant cells, with negligible impact on their healthy counterparts, leading to high-rate apoptotic death of malignant cells in vitro and in clinically relevant in vivo models. 研究人员正在探索诸如此类的发现，以开发新的策略，改善目前减轻肿瘤发生风险的选择, overcoming drug resistance, and enhancing prognosis of patients who receive current anticancer therapies.

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Cold Plasma Bioengineering

Cold plasma produces diverse biologically active agents, including reactive species, ions, photons, and will affect transient electric fields that are also produced endogenously by eukaryotic cells. This similarity has fueled extensive exploitation of its benefits to human health, 导致冷等离子体为基础的程序在凝血和消融的临床应用，并在临床试验中治疗伤口, head and neck cancers, and autoimmune skin disorders. Here at the Center for Bioelectrics, 研究人员设计冷等离子体化学来复制和利用内源性反应物质和离子的有益生物效应，以获得新的解决方案，可以改善癌症患者的预后.g. pancreatic, leukemia, breast, skin cancers), infection, and injured organs. Through multidisciplinary collaboration, we focus on (1) dose-controlled delivery of cold plasma and plasma-activated solution; (2) their effects on the mammalian host's immune response and energy requirement; (3) their molecular and cellular targets in pathological or regenerative tissues; (4) their benefits as a monotherapy for cancer, infection and injury or as a drug-delivery method for gene immunotherapy; and (5) their synergy with other bioengineering platforms such as pulsed electric field. Furthermore, investigators at the Center are interested in cold plasma-based infection control in agriculture and environment settings.

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Microbial Disinfection

已知微生物易受冷等离子体和脉冲电场(PEF)诱导的氧化应激和膜穿孔的影响。, respectively. 在生物电学中心，冷等离子体和PEF正在发展成为两种互补的生物工程技术, they are being advanced toward patient benefits. Against antibiotic resistance, 该中心的研究人员已经开发出一种血浆活化溶液(PAS)，在不伤害哺乳动物细胞的情况下，将耐药细菌和真菌的数量减少7-log10. This is significant given that these pathogens are resistant to all current antibiotics. Further, PAS被设计用于去除胃肠道内窥镜通道和中心静脉导管内形成的细菌生物膜. Recognizing the current lack of effective eradication of in vivo microbial biofilm, implicated in diabetic foot ulcers and chronic obstructive pulmonary disease, 该中心的研究人员开发了一种基于pas的伤口敷料疗法，并证明了其在破坏MRSA伤口生物膜方面的有效性和安全性, the culprit responsible for life-threatening bacteremia. Further, these discoveries are being expanded to meet the challenge of disinfection beyond medicine, for example PEF-reduced biofouling control of liquid food (e.g., orange juice), PAS-enhanced animal food safety, and PAS-based control of COVID spread by inactivating SARS-CoV-2 binding with human cells.

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Cold Plasma-Based Regenerative Medicine

Of diverse reactive species and ionic species produced by cold plasma, hydrogen peroxide and nitric oxide are known to promote cell proliferation and angiogenesis, respectively. These contribute to the basis of multiple successful clinical studies of cold plasma for wound healing. Interestingly, cold plasma activates, in a dose-dependent fashion, major signaling pathways important in regenerative medicine, for example Nrf2 for abatement of excessive oxidative stress common in injured tissues, Wnt for migration of stem cells, and HIF-1 alpha for angiogenesis. These studies suggest that cold plasma may be applicable beyond skin wounds. As an example, 生物电学中心的研究人员发现，冷等离子体通过提高细胞抗氧化能力，引发神经保护，防止谷氨酸兴奋性毒性, a desirable function for treatment of stroke and spinal cord injury. 在白癜风的情况下，失调的T细胞攻击黑素细胞导致皮肤脱色，并且无法治愈, investigators innovated a gel prepared with cold plasma that disrupts T cell attack on melanocytes, arrests excessive oxidative stress, and promotes re-pigmentation of vitiligo lesion in animal models. This in vivo efficacy is successfully demonstrated in a controlled and randomized clinical trial. Current focus is to improve mechanistic insights and translational readiness.

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HSP90 inhibitors modulate Acute and Chronic Lung Injury

Acute Lung Injury (ALI), acute respiratory distress syndrome (ARDS) and Pulmonary Fibrosis (PF) are major determinates of morbidity and mortality. FDA-approved therapeutic interventions are limited, and new drugs are thus needed. Heat Shock Proteins (HSP) are chaperones that assist a high number of client proteins during their folding, stabilization and/or degradation. HSP90, the most ubiquitous protein of the family, plays a major role during lung injury and inflammation. Indeed, HSP90 is a critical regulator of pulmonary endothelial permeability and modulates key proteins, including RhoA, ROCK1, cofilin and VE-cadherin, thus participating in the development of alveolar edema. Consequently, HSP90 inhibitors control at multiple levels both inflammation and lung injury. Among the >400 client proteins, HSP90 stabilizes Transforming Growth Factor-β (TGF-β), its receptor and Raf, ERK and Smads signaling, that are directly involved in the development of chronic lung injury. HSP90 inhibitors reduce mortality in several animal models of ALI and prevent the development of Pulmonary Fibrosis. Further investigations are required to establish optimal dose strategy, potency, and therapeutic schemes of the various new HSP90 inhibitors.

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