Research interests

Personal research entails (1) site-specific pharmaco-laser therapy for oncological indications, (2) development of liposomal oxygen-, reactive oxygen species-, mitochondrial permeability-, and pH-sensors, (3) the development of liposomal drug delivery systems to reduce the pathological effects associated with steatosis, cholestasis, and ischemia/reperfusion injury, and (4) light-based modalities for the treatment of solid tumors. Additional research activities are focused on the following areas: (1) hepatic and renal ischemia/reperfusion injury; (2) hepatic steatosis; (3) cholestasis; (4) portal vein embolization and liver regeneration; (5) liver and kidney transplantation and preservation techniques; (6) chemotherapy and photodynamic therapy of solid cancers; (7) laser-assisted vascular welding; and (8) hibernation. These projects are typically carried out by master/medical and PhD students under my supervision. Research responsibilities further include development and employment of micro- and spectroscopic techniques for the assessment of cell/tissue viability and function as well as setting up novel animal models and biochemical/chemical assays, treatment techniques, and research lines within the scope of existing and novel research activities. Other duties include the supervision of PhD and bachelor/master students, lecturing, management of the analytical team, and acquisition of research funding.

Keywords: oncology: chemotherapy, photodynamic therapy, liposomal drug delivery systems; hepatology: ischemia-reperfusion, oxidative/nitrosative stress, portal vein embolization, liver regeneration, steatosis, cholestasis, preservation techniques; nanoparticulate drug delivery: site-specific pharmaco-laser therapy, port wine stains, solid cancers, hepatotargeting, fluorescent probes for oxidative stress / pH / MPT / pO2; nephrology: organ preservation and transplantation; vascular surgery: laser-assisted vascular welding.

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CURCUMIN RESEARCH

Curcumin is a biologically active compound derived from the root of the Curcuma longa plant. Curcumin has very broad pharmacodynamic activity but a very poor pharmacokinetic profile. Extensive research has been performed on the use of curcumin for the treatment of cancer, as it is capable of interfering with all the hallmarks of cancer. This makes curcumin a chemopreventive, oncostatic, and antimetastatic agent. Interestingly, curcumin appears to be toxic to cancer cells but cytoprotective to healthy cells. Multiple studies have also shown its efficacy in combating ageing and various forms of neurodegenerative, infectious, and auto-immune disease. As a pharmaceutical, however, curcumin is far less idyllic. The compound is photolabile, insoluble in water, and susceptible to hydrolysis and oxidation. Moreover, it is poorly taken up from the intestinal system and subject to biotransformation once it has entered the circulation.

Curcumin is well tolerated by patients (up to 12 g/day) and can be stabilized by dark conditions and high acidity. Accordingly, curcumin performs relatively well in patients with colon cancer. The stomach and intestines are dark and acidic, and due to the poor uptake the compound resides in close proximity to neoplastic/malignant enteral tissue.

For other types of cancer, however, curcumin must be either chemically modified or encapsulated into a drug delivery system. In that respect, our curcumin-related research focuses primarily on the development of tumor-targeting liposomes that deliver curcumin to the cancer following i.v. administration. Furthermore, we are identifying novel molecular targets of curcumin via molecular dynamics simulations and molecular/cell biology techniques and investigating specific elements of its pharmacokinetic behavior. This research, which is sponsored by the Stichting Nationaal Fonds tegen Kanker and the Nijbakker Morra Stichting, is performed in collaboration with colleagues at the AMC and the University of Utrecht as part of the International Curcumin Research initiative.

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