Stefan Bossmann

Research

Overview

Protease Signatures for Early Cancer Diagnostics and Cancer Therapy Decisions
Serine, cysteine, and aspartic proteases are markers for the ability of many cancers to grow and to form metastases. Several serine, cysteine and aspartic proteases are over-expressed by numerous cancer cell lines. Elevated expression levels of urokinase and several other components of the plasminogen activation system are found to be correlated with tumor malignancy. This diagnostic assay is comprised of protease-sensitive cleavage sequences for up to 30 proteases, which are used as linkers between two fluorophores (nanoparticles and/or organic or inorganic dyes). Depending on the nanoparticles and dyes used, optical (fluorescence), magnetic (MRI), and x-ray imaging of the tumor location and extension can be performed, together with quantitative determination of the proteases' activities. Similar assays are being developed for enzymes capable of posttranslational modification (arginase and kinases), as well as important viruses (COVID-19, HPV).
Imaging of Biophysical Barriers in Cancer, Spectral Imaging, and Micrometastases
Ultra-high-resolution imaging techniques (micro-CT, ultra-high-field MRI and optical tomography) permit the imaging of biophysical barriers in cancer (e.g. interstitial collagen and hyaluronic acid deposits), as well as the directional diffusion characteristics of stromal interfaces. This will permit the quantitative understanding of drug transport into tumors in preclinical models, followed by clinical translation. Spectral MRI imaging enables simultaneous voxel-by-voxel pharmacokinetics, as well as the observation of metabolic changes in cancer. By using contrast-marker free ultra-high field MRI techniques, micrometastases can be quantitatively imaged. Any successful treatment methods of solid tumors have to block and reverse the formation of micrometastases, which otherwise can grow to metastases and are responsible for the majority of mortalities from cancer.
Advanced Drug Delivery and Drug Delivery Materials
My research has been concerned with various types of vesicles for drug delivery purposes (against cancer and infectious diseases, such as Mycobacterium tuberculosis and Methicillin-resistant Staphylococcus aureus) since 2004. Recently, we have discovered a new class of copper(I)-binding drugs with so-called NNSN-motif that feature nanomolar activities against solid pancreatic cancer and glioblastoma. We also have established rationally designed peptide nanosponges as versatile nanosystems for drug delivery to tumors and defensive cells. My group also has experience in synthesizing tailored magnetic and carbon nanomaterials derived from detonation-graphene.

• Murphy, Cathy., J., Arkin, Michelle., R., Jenkins, Yunju , Ghatlia, Naresh , Bossmann, Stefan., H., Turro, Nicholas., J., Barton, Jaqueline., K.. 1993. Long-range photoinduced electron transfer through a DNA helix.. Science (262), 1025-9
• Woerner, Michael, Lioubashevski, Oleg, Basel, Matthew., T., Niebler, Sandra, Gogritchiani, Eliso, Egner, Nicole, Heinz, Christian, Hoferer, Juergen, Cipolloni, Michela, Janik, Katharine, Katz, Evgeny, Braun, Andre., M., Willner, Itamar, Niederweis, Michael, Bossmann, Stefan., H.. 2007. Characterization of nanostructured surfaces generated by reconstitution of the porin MspA from Mycobacterium smegmatis. SMALL, 3 (6), 1084-1097
• Shrestha, Tej., B., Seo, Gwi., M., Basel, Matthew., T., Kalita, Mausam, Wang, Hongwang, Villanueva, David, Pyle, Marla, Balivada, Sivasai, Rachakatla, Raja., Shekar, Shinogle, Heather, Thapa, Prem., S., Moore, David, Troyer, Deryl., L., Bossmann, Stefan., H.. 2012. Stem cell-based photodynamic therapy. PHOTOCHEMICAL & PHOTOBIOLOGICAL SCIENCES, 11 (7), 1251-1258
• Alshetaiwi, Hamad., S., Balivada, Sivasai, Shrestha, Tej., B., Pyle, Marla, Basel, Matthew., T., Bossmann, Stefan., H., Troyer, Deryl., L.. 2013. Luminol-based bioluminescence imaging of mouse mammary tumors. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 127, 223-228
• Udukala, Dinusha., N., Wang, Hongwang, Wendel, Sebastian., O., Malalasekera, Aruni., P., Samarakoon, Thilani., N., Yapa, Asanka., S., Abayaweera, Gayani, Basel, Matthew., T., Maynez, Pamela, Ortega, Raquel, Toledo, Yubisela, Bossmann, Leonie, Robinson, Colette, Janik, Katharine., E., Koper, Olga., B., Li, Ping, Motamedi, Massoud, Higgins, Daniel., A., Gadbury, Gary, Zhu, Gaohong, Troyer, Deryl., L., Bossmann, Stefan., H.. 2016. Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection. BEILSTEIN JOURNAL OF NANOTECHNOLOGY, 7, 364-373
• Malalasekera, Aruni., P., Wang, Hongwang, Samarakoon, Thilani., N., Udukala, Dinusha., N., Yapa, Asanka., S., Ortega, Raquel, Shrestha, Tej., B., Alshetaiwi, Hamad, McLaurin, Emily., J., Troyer, Deryl., L., Bossmann, Stefan., H.. 2017. A nanobiosensor for the detection of arginase activity. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, 13 (2), 383-390
• Yapa, Asanka., S., Wang, Hongwang, Wendel, Sebastian., O., Shrestha, Tej.., B., Kariyawasam, Nilusha., L., Kalubowilage, Madumali, Perera, Ayomi., S., Pyle, Marla, Basel, Matthew., T., Malalasekera, Aruni., P., Manawadu, Harshi, Yu, Jing, Toledo, Yubisela, Ortega, Raquel, Thapa, Prem., S., Smith, Paul., E., Troyer, Deryl., L., Bossmann, Stefan., H.. 2018. Peptide nanosponges designed for rapid uptake by leukocytes and neural stem cells. RSC ADVANCES, 8 (29), 16052-16060
• Crawford, Cameron., L., Dalecki, Alex., G., Narmore, Whitney., T., Hoff, Jessica, Hargett, Audra., A., Renfrow, Matthew., B., Zhang, Man, Kalubowilage, Madumali, Bossmann, Stefan., H., Queern, Stacy., L., Lapi, Suzanne., E., Hunter, Robert N., III, Bao, Donghui, Augelli-Szafran, Corinne., E., Kutscha, Olaf, Wolschendorf, Frank. 2019. Pyrazolopyrimidinones, a novel class of copper-dependent bactericidal antibiotics against multi-drug resistant S. aureus. METALLOMICS, 11 (4), 784-798
• Covarrubias-Zambrano, Obdulia, Yu, Jing, Bossmann, Stefan., H.. 2020. Nano-Inspired Technologies for Peptide Delivery. CURRENT PROTEIN & PEPTIDE SCIENCE, 21 (4), 379-400
• Payne, Macy, Bossmann, Stefan., H., Basel, Matthew., T.. 2020. Direct treatment versus indirect: Thermo-ablative and mild hyperthermia effects. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 12 (5), e1638