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Department of Chemistry

Dr. Stefan Bossmann

stefan

Professor

M.S., University of Saarland, Germany (1988)
Ph.D., University of Saarland, Germany (1991)
Postdoctoral Research Fellow, Columbia University (1991-3)
Professor, University of Karlsruhe (1993-2004)

Email: sbossman@ksu.edu
Office Phone: 785-532-6817
Lab Phone: 785-532-3090 (3rd Floor)
Lab Phone: 785-532-6672 (4th Floor)
Fax: 785-532-6666

Website: Bossmann Group

 

Recent Awards, Honors and Donations

  •  “STEM Research Exemplar” by The Research Exemplar Project of the Washington University School of Medicine in St. Louis in 2017 (http://integrityprogram.org/exemplar-project/stem-exemplars/).
  • Erwin W. Segebrecht Award for Excellence and Inspiration in Teaching, Research, and Service in 2017.
  • Funding by NSF (EAGER with Prof. Dr. Culbertson at Kansas State in 2016), NIH (R01 with Prof. Dr. Wolschendorf, University of Alabama at Birmingham in 2016, COBRE with Department of Psychology in 2017), Anticipate Ventures, LLC (with Prof. Dr. Sorensen, Physics at Kansas State) and private donations (Eric Stonestreet).

 

Research Overview

  1.      Cell-Mediated Delivery of Drugs to Tumors
  2.      Image-Guided Hyperthermia of Solid Tumors
  3.      Liquid Biopsies for Early Stage Solid Tumors
  4.      Design of a Point-of-Care (POC) Detection Device
  5.      Copper Activated Drugs Against Gram-positive Bacteria
  6.      Transforming Printmaking through Chemical Innovation

 

Cell-Mediated Delivery of Drugs to Tumors In collaboration with Deryl L. Troyer, we have pioneered the use of stem cells and defensive cells, which actively migrate to tumors, as transport modalities to effectively target tumors and metastases.1-5We were the first team utilizing stem cells for the transport of nanoformulations to solid tumors.6 We also hold the US record for maximizing the survival times of mice bearing pancreatic tumors by means of cell-mediated hyperthermia.7 Recently, we have developed peptide-based nanosponges for the delivery of drugs, DNA, and RNA to leucocytes in peripheral blood.8 The design of the nanosponges was sparked by a CREATIVE grant from the National Science Foundation.

 

 Video: https://www.youtube.com/watch?v=qo3HFew0hc0

 

 

Cell-Based Cancer Therapy in Mice using Hyperthermia as treatment modality

Figure 1: (from reference 7)
A: Hoechst nuclear counterstained section shows monocyte/macrophage-like cells labeled with PKH26 (red) in a pancreatic tumor
B: Hematoxylin and eosin staining indicates irregular morphology (same field of view as in A)
C: Cell-Based Cancer Therapy in Mice using Hyperthermia as treatment modality

 

Mouse Survival Study: Cell-Mediated Hyperthermia in Mice

Figure 2: (from reference 7)
A: Cell-Mediated Hyperthermia in Mice: A/C-magnetic hyperthermia leads to modest temperature increase in the tumor, leading to immune activation
B: Mouse Survival Study: Cell-delivered Fe/Fe3O4-nanoparticles show synergy with A/C-magnetic hyperthermia.

 

Image-Guided Hyperthermia of Solid TumorsIn collaboration with Deryl L. Troyer, and Punit Prakash, we have developed an integrated platform for small-animal hyperthermia investigations under ultra-high field MRI guidance.9 This platform enables us to optimize the effect of immune-stimulating hyperthermia on solid tumors and to observe the migration of defensive cell populations into tumors and metastases. Furthermore, we have optimized this technology to detect micrometastases (< 2mm in diameter). To the best of our knowledge, this is the first time when micrometastases could be detected by means of Magnetic Resonance Imaging. This was made possible by a 600MHz (14.1T) NMR/MRI from the National Science Foundation. I have summarized this endeavor in a recent presentation at the Coffman Foundation in Kansas City, as well as the approach to liquid biopsies for cancer detection

 

Video: https://vimeo.com/187739690

 

 MRI Facility @Bossmann Group

Figure 3: (from reference 9)
A: Photograph of the vertical MRI scanner (Bruker Ascend)
B: MRI micro-imaging probe with the microwave applicator
C: Applicator positioned adjacent to an experimental animal (BALB/c mouse bearing a 4T1 tumor).

 

 MRI Images of in vivo microwave exposure

Figure 4: (from reference 9)
Anatomical image depicting the microwave applicator and implanted subcutaneous tumor (left) and transient evolution of spatial temperature profiles during and after 15 min of in vivo microwave exposure at 20 W input power.

 

T2_TurboRARE pulse sequence of a BALB/c mouse and analyses

Figure 5: First MR Image of Micrometastases in Syngeneic Mice, recorded by Dr. Tej B. Shrestha
Left: T2_TurboRARE pulse sequence of a BALB/c mouse bearing 4T1 micrometastases in the lung.
Right:
Quantitative analysis of the micrometastases utililizing the MIPAV software package from NIH. The longest axes of the micrometastases are 0.33 mm and 0.42 mm.
 

 

Liquid Biopsies for Early Stage Solid Tumors (Breast, Lung, Pancreatic, and Thyroid Cancers)  The synthesis of tailored Fe/Fe3O4 nanoparticles, which are dispersible and sufficiently stable in aqueous buffers has enabled the design of ultrasensitive nanobiosensors for the detection of multiple proteases (ADAM’s, cathepsins, caspases, granzymes and matrix metalloproteinases), and enzymes capable of post-translational detection (multiple kinases and arginase) with sub-femtomolar limits of detection.10-12 We have developed a methodology for liquid biopsies using serum from cancer patients, which permits the detection of stage 1 breast-, lung-, and pancreatic-  cancers with more than 95% accuracy. Stage 0 detection is currently being developed.  The development of liquid biopsies for solid tumor detection at the earliest stages is performed in collaboration with Anup Kasi, and Stephen Williamson, University of Kansas Medical Center and with Gaohong Zhu, head of Radiology of the First Affiliated Hospital of Kunming Medical University, China, where we have carried out two successful clinical trials in 2014 to 2016, with a total of more than 15,000 patients. We were able to identify protease signatures for 11 types of solid tumors. KSURF holds the patents for this technology.

 

 
Video: https://www.youtube.com/watch?v=n9-_RloH-S8

 

Design of a Point-of-Care (POC) Detection Device In collaboration with Dr. Christopher T Culbertson, we are developing a POC Device for simultaneous protease, kinase and cytokine detection, which is based on isoelectric focusing. This system will be characterized by potential enzyme amplification, analyte volume reduction and focused detection bands thus permitting limits of detection (LOD) improvements of 106, so that the detection of analytes at the fM and sub-fM levels becomes feasible. Additionally, the capability of multiplexing, high peak capacity and the ability to independently alter the band placement allows a large number of analytes to be analyzed. This is necessary to detect and identify the subtle changes that take place early in the progression of a disease.  In collaboration with Allan Brasier and Massoud Motamedi (UTMB), we have established the company Mobile Biosensing Diagnostics LLC in 2017 as a Joint Venture of KSU and UTMB. The contract establishingMobile Biosensing Diagnostics LLC was signed in August 2017.

 

Video: https://www.youtube.com/watch?v=JSqynTb5t0k

 

Copper Activated Drugs Against Gram-positive Bacteria

Copper-activated drugs against Methicillin-resistant Staphylococcus aureus (MRSA) and, potentially, other multi-resistant pathogens, increase significantly in their efficacy when forming copper(I) complexes. They are very promising in the uphill battle against infectious diseases, because they utilize copper(I), which is provided as a cellular response to bacterial infections within phagosomes.13 This strategy is part of the "nutritional immunity response", in which the host cells attempt to sequester vital nutrients of the invading pathogens, while increasing the concentration of toxic copper(I). This research is conducted in close collaboration with Assistant Prof. Dr. Frank Wolschendorf, Departments of Medicine and Microbiology, at the University of Alabama at Birmingham. We have identified a novel type of thiourea compounds with NNSN-motif.14-16 Upon complexation with Copper I, an iminium cation is formed, which is a well-known reactive intermediate in numerous org. reactions. It is our paradigm that this reactive group is capable of acting as a warhead and/or can facilitate DNA-intercalation.

 

Compounds with NNSN-motif take advantage of nutritional immunity

Figure 6:Compounds with NNSN-motiftake advantage of nutritional immunity (from reference16)

 

Transforming Printmaking through Chemical Innovation In collaboration with Jason Scuilla, master printmaker and Associate Professor in the Kansas State Department of Arts. To date, most of the procedures that are being used in the arts closely resemble alchemic procedures, with little understanding of the manifold of the underlying electrochemical reactions and only modest regard for safety considerations. Since 2014, we are implementing well-established electrolytic etching processes from the semiconductor- and computer industry in Jason’s art studio. These procedures do not only provide professional safety standards in the art studio, they also allow the artist to tailor the electrochemical conditions to fine-tune artistic expressions.  This approach is guided by the paradigm that the best art can be created by mastering the required technique(s).


 

Selected Publications

1. Balivada, S.; Rachakatla, R. S.; Wang, H.; Samarakoon, T. N.; Dani, R. K.; Pyle, M.; Kroh, F. O.; Walker, B.; Leaym, X.; Koper, O. B.; Tamura, M.; Chikan, V.; Bossmann, S. H.; Troyer, D. L., A/C magnetic hyperthermia of melanoma mediated by iron(0)/iron oxide core/shell magnetic nanoparticles: a mouse study. BMC Cancer 2010,10, No pp. given.
2. Wang, H.; Shrestha, T. B.; Basel, M. T.; Dani, R. K.; Seo, G.-M.; Balivada, S.; Pyle, M. M.; Prock, H.; Koper, O. B.; Thapa, P. S.; Moore, D.; Li, P.; Chikan, V.; Troyer, D. L.; Bossmann, S. H., Magnetic-Fe/Fe3O4-nanoparticle-bound SN38 as carboxylesterase-cleavable prodrug for the delivery to tumors within monocytes/macrophages. Beilstein J. Nanotechnol. 2012,3, 444-455, 12 pp.
3. Alshetaiwi, H. S.; Balivada, S.; Shrestha, T. B.; Pyle, M.; Basel, M. T.; Bossmann, S. H.; Troyer, D. L., Luminol-based bioluminescence imaging of mouse mammary tumors. J. Photochem. Photobiol., B 2013,127, 223-228.
4. Basel, M. T.; Shrestha, T. B.; Bossmann, S. H.; Troyer, D. L., Cells as delivery vehicles for cancer therapeutics. Ther. Delivery 2014,5 (5), 555-567.
5. Wang, H.; Shrestha, T. B.; Basel, M. T.; Pyle, M.; Toledo, Y.; Konecny, A.; Thapa, P.; Ikenberry, M.; Hohn, K. L.; Chikan, V.; Troyer, D. L.; Bossmann, S. H., Hexagonal magnetite nanoprisms: preparation, characterization and cellular uptake. J. Mater. Chem. B 2015,3 (23), 4647-4653.
6. Rachakatla, R. S.; Balivada, S.; Seo, G.-M.; Myers, C. B.; Wang, H.; Samarakoon, T. N.; Dani, R.; Pyle, M.; Kroh, F. O.; Walker, B.; Leaym, X.; Koper, O. B.; Chikan, V.; Bossmann, S. H.; Tamura, M.; Troyer, D. L., Attenuation of Mouse Melanoma by A/C Magnetic Field after Delivery of Bi-Magnetic Nanoparticles by Neural Progenitor Cells. ACS Nano 2010,4 (12), 7093-7104.
7. Basel, M. T.; Balivada, S.; Wang, H.; Shrestha, T. B.; Seo, G. M.; Pyle, M.; Abayaweera, G.; Dani, R.; Koper, O. B.; Tamura, M.; Chikan, V.; Bossmann, S. H.; Troyer, D. L., Cell-delivered magnetic nanoparticles caused hyperthermia-mediated increased survival in a murine pancreatic cancer model. Int. J. Nanomed. 2012,7, 297-306.
8. Wang, H.; Yapa, A. S.; Kariyawasam, N. L.; Shrestha, T. B.; Kalubowilage, M.; Wendel, S. O.; Yu, J.; Pyle, M.; Basel, M. T.; Malalasekera, A. P.; Toledo, Y.; Ortega, R.; Thapa, P. S.; Huang, H.; Sun, S. X.; Smith, P. E.; Troyer, D. L.; Bossmann, S. H., Rationally designed peptide nanosponges for cell-based cancer therapy. Nanomedicine (N. Y., NY, U. S.) 2017, Ahead of Print.
9. Curto, S.; Faridi, P.; Shrestha, T.; Pyle, M.; Maurmann, L.; Troyer, D.; Bossmann, S.; Prakash, P., An integrated platform for small-animal hyperthermia investigations under ultra-high field MRI guidance. Int. J. Hyperthermia 2017,ahead of print.
10. Wang, H.; Udukala, D. N.; Samarakoon, T. N.; Basel, M. T.; Kalita, M.; Abayaweera, G.; Manawadu, H.; Malalasekera, A.; Robinson, C.; Villanueva, D.; Maynez, P.; Bossmann, L.; Riedy, E.; Barriga, J.; Wang, N.; Li, P.; Higgins, D. A.; Zhu, G.; Troyer, D. L.; Bossmann, S. H., Nanoplatforms for highly sensitive fluorescence detection of cancer-related proteases. Photochem. Photobiol. Sci. 2014,13 (2), 231-240.
11. Udukala, D. N.; Wang, H.; Wendel, S. O.; Malalasekera, A. P.; Samarakoon, T. N.; Yapa, A. S.; Abayaweera, G.; Basel, M. T.; Maynez, P.; Ortega, R.; Toledo, Y.; Bossmann, L.; Robinson, C.; Janik, K. E.; Koper, O. B.; Li, P.; Motamedi, M.; Higgins, D. A.; Gadbury, G.; Zhu, G.; Troyer, D. L.; Bossmann, S. H., Early breast cancer screening using iron/iron oxide-based nanoplatforms with sub-femtomolar limits of detection. Beilstein J. Nanotechnol. 2016,7, 364-373.
12. Malalasekera, A. P.; Wang, H.; Samarakoon, T. N.; Udukala, D. N.; Yapa, A. S.; Ortega, R.; Shrestha, T. B.; Alshetaiwi, H.; McLaurin, E. J.; Troyer, D. L.; Bossmann, S. H., A nanobiosensor for the detection of arginase activity. Nanomedicine (N. Y., NY, U. S.) 2017,13 (2), 383-390.
13. Wolschendorf, F.; Ackart, D.; Shrestha, T. B.; Hascall-Dove, L.; Nolan, S.; Lamichhane, G.; Wang, Y.; Bossmann, S. H.; Basaraba, R. J.; Niederweis, M., Copper resistance is essential for virulence of Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U. S. A. 2011,108 (4), 1621-1626, S1621/1-S1621/31.
14. Speer, A.; Shrestha, T. B.; Bossmann, S. H.; Basaraba, R. J.; Harber, G. J.; Michalek, S. M.; Niederweis, M.; Kutsch, O.; Wolschendorf, F., Copper-boosting compounds: a novel concept for antimycobacterial drug discovery. Antimicrob. Agents Chemother. 2013,57 (2), 1089-1091.
15. Haeili, M.; Moore, C.; Davis, C. J. C.; Cochran, J. B.; Shah, S.; Shrestha, T. B.; Zhang, Y.; Bossmann, S. H.; Benjamin, W. H.; Kutsch, O.; Wolschendorf, F., Copper complexation screen reveals compounds with potent antibiotic properties against methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. 2014,58 (7), 3727-3736, 11 pp.
16. Dalecki, A. G.; Malalasekera, A. P.; Schaaf, K.; Kutsch, O.; Bossmann, S. H.; Wolschendorf, F., Combinatorial phenotypic screen uncovers unrecognized family of extended thiourea inhibitors with copper-dependent anti-staphylococcal activity. Metallomics 2016,8 (4), 412-421.