Cancer is a group of diseases which are characterized by abnormal cellular growth and they collectively constitute one of the leading causes of morbidity and mortality on a global scale. While there has been a considerable progress in the development of improved cancer therapeutics and treatment strategies over the years, the traditional approaches still widely applied today lead to suboptimal treatment outcomes in many cases. As a result, the development of novel pharmaceuticals and medical technologies which are capable to deliver improved treatment outcomes are appealing and consequently on the rise worldwide. It should be noted that chemistry plays a central role to the success of all drug development campaigns. Chemistry is utilized at early-phase drug discovery to design, synthesize and engineer molecules which interact precisely with the intended biological targets and to optimize the performance of drug candidates through structural modifications leading to enhanced potency, selectivity and safety.
Figure. In our drug discovery programs, we employ modern medicinal chemistry approaches in the design and development of improved molecular solutions for distinct diseases such as cancers. In the Figure, the key scientific techniques employed are highlighted: synthetic organic chemistry, structural characterization, molecular recognition studies, in vitro cellular studies, imaging and in vivo animal studies. Biorender has been utilized to create certain images in the Figure.
In the Biomolecular Chemistry group, we employ chemistry-empowered approaches in early-stage drug discovery projects aligned with the core principles of precision medicine. Our work has focused on in-depth structural and conformational analysis of cytotoxic payload molecules which are utilized in state-of-the-art cancer therapeutics such as antibody-drug conjugates. Moreover, our team specializes in the development of boron delivery agents for boron neutron capture therapy (BNCT). BNCT stands out as a promising cancer therapy due to its selectivity (eradication of cancer cells with minimal effects on healthy cells) and applicability (tumors where surgery and other treatment options are not effective can be treated) and improving the performance and selectivity of boron delivery agents may lead to significant scientific breakthroughs in treatment of distinct cancers and the widespread use of BNCT. Recently, we successfully completed an early-stage drug-discovery project focusing on the preclinical assessment of the potential embedded in carbohydrate delivery agents for BNCT together with our collaboration partners from the fields of radiopharmaceutical chemistry, computational chemistry, cancer biology and pharmacy. Currently, we are focusing our efforts on the development of innovative boron delivery agents for emerging biological targets which hold significant promise in treatment of distinct cancers. Stay tuned for updates on our journey towards supplying the medical community with improved boron delivery agents!
The eye, one of Nature’s greatest inventions to help organisms navigate in the biosphere, is an intriguing biological construct and the result of millions of years of evolution. In the eye, a myriad of advanced and aligned biological processes are working together to convert the incoming light to images which we perceive as vision. The outermost layer of the tear film covering the eye, the tear film lipid layer (TFLL), is currently viewed as essential to the maintenance of ocular health. This nanometers thin complex biofilm mainly secreted by the meibomian glands is present in a challenging environment as it forms a protective barrier between the aqueous tear film and the air. Versatile functions ranging from retardation of water loss and provision of lubrication during eye blink cycles to stabilization of the tear film and sustenance of the optimal refractive index required for clear vision have been reported for the TFLL. Due to the location of the TFLL and the importance of vision, these functions need to be guaranteed regardless of environmental conditions and restored within milliseconds whenever the eye is opened. The surroundings and mode of action of the TFLL is thus different from that of conventional biological membranes and evolution has resulted in a highly adaptive biofilm composed of hundreds of lipids and other biomolecules. Surprisingly, despite the importance of the TFLL, there are no scientifically validated and widely accepted models available concerning its molecular level structure and function. Supplying this information is not only viewed as a considerable scientific challenge, it is the prerequisite for the future development of improved diagnostics and therapeutics for ocular surface disorders which affect a growing number of the global population and constitute a significant public healthcare challenge and societal economic burden.
Figure. In our ocular surface research program, we have utilized a multidisciplinary approach to generate an improved understanding of the structure, properties and potential roles of tear film lipids. In the Figure, the key scientific techniques employed are highlighted: synthetic organic chemistry, structural characterization, biophysical profiling, profiling through surface scattering techniques, in vitro cellular studies and in vivo animal studies. Biorender has been utilized to create certain images in the Figure.
In 2017, we established a research program based upon a unique and sophisticated chemistry-biophysics approach in order to unravel the molecular level mysteries surrounding the TFLL. Since then, we have become the first research team in the world that has systematically synthesized, characterized and performed detailed biophysical profiling studies on the main tear film lipid classes simultaneously generating insights on their intermolecular interactions, collaborative mode of action and potential roles in a functional TFLL. The research program has been supported by governmental funding agencies and private foundations over the years and has generated significant scientific and societal impact in the form of high-quality scientific reports, innovations and novel technologies for treatment of ocular surface disorders and providing excellent educational and training opportunities for the next generation of biomolecular chemists. We are currently transitioning into the final phase of the research program and expect to continue to contribute to significant scientific breakthroughs in understanding the link between TFLL organization and function which in time will translate into improved diagnostic tools and treatments for ocular surface disorders. Follow and support us on our journey as we work towards these goals!