Featured Scholar: Nathan J. Alves, PhD, MS
Assistant Professor of Emergency Medicine, IU School of Medicine
CEO of Indiana Lysis Technologies, LLC
Safer Clot Digestion through Nanotechnology
Venous thromboembolism (VTE) is a blood clot disorder that encompasses two related conditions-pulmonary embolism (blood clots in lungs) and deep vein thrombosis (DVT). According to the Centers for Disease Control and Prevention, VTE affects 900,000 people each year in the United States. One treatment method for VTE is enzyme-based pharmaceutical agents that dissolve the clot. All available clot-dissolving enzymes rely on the activation of the patient's innate clot-digesting system. This nonspecific clot digestion, which results in uncontrolled clearance of both the clot of interest and beneficial clots throughout the body, leads to bleeding complications, including intracranial hemorrhage, in 5-10 percent of patients.
Dr. Nathan Alves, the first tenure-track PhD faculty member primarily appointed in the Department of Emergency Medicine, along with IU colleague Dr. Jeffrey Kline, founded Indiana Lysis Technologies LLC (ILT) to develop and commercialize safer clot-digesting therapeutics to better control clot digestion and reduce the risk of off-target bleeding. The interdisciplinary nature of Dr. Alves' work, which spans the basic sciences, medicine, and engineering, facilitated the development of a targeted nanoparticle enzyme delivery system to clear blood clots.
ILT placed third in the 2017 BioCrossroads New Venture Competition and won "Best Biotech Invention" in the 2018 Notre Dame McCloskey Business Plan Competition.
Dr. Alves' work in developing next generation nanoparticle-based clot dissolving pharmaceuticals is another example of how IUPUI faculty are TRANSLATING RESEARCH INTO PRACTICE.
Selected Publications in IUPUI ScholarWorks
With several research works contributed to IUPUI's free, open access repository, Professor Stephanie Andel has made translational research knowledge available to professionals, researchers, students, and communities around the world.
Alves, N. J. (2019). Antibody Conjugation and Formulation. Antibody Therapeutics. http://hdl.handle.net/1805/18634
Chelvanambi, S., Bogatcheva, N. V., Bednorz, M., Agarwal, S., Maier, B., Alves, N. J., … Clauss, M. (2018). HIV-Nef Protein Persists in the Lungs of Aviremic Patients with HIV and Induces Endothelial Cell Death. American Journal of Respiratory Cell and Molecular Biology, 60(3), 357–366. http://hdl.handle.net/1805/20026
Hondred, J. A., Breger, J. C., Alves, N. J., Trammell, S. A., Walper, S. A., Medintz, I. L., & Claussen, J. C. (2018). Printed Graphene Electrochemical Biosensors Fabricated by Inkjet Maskless Lithography for Rapid and Sensitive Detection of Organophosphates. ACS Applied Materials & Interfaces, 10(13), 11125–11134. http://hdl.handle.net/1805/19951
Alves, N. J., Moore, M., Johnson, B. J., Dean, S. N., Turner, K. B., Medintz, I. L., & Walper, S. A. (2018). Environmental Decontamination of a Chemical Warfare Simulant Utilizing a Membrane Vesicle-Encapsulated Phosphotriesterase. ACS Applied Materials & Interfaces. http://hdl.handle.net/1805/16146
Zaretsky, D. V., Kline, H., Zaretskaia, M. V., Brown, M. B., Durant, P. J., Alves, N. J., & Rusyniak, D. E. (2018). Disinhibiting neurons in the dorsomedial hypothalamus delays the onset of exertional fatigue and exhaustion in rats exercising in a warm environment. Brain Research, 1689, 12–20. http://hdl.handle.net/1805/15883
Alves, N. J., Turner, K. B., DiVito, K. A., Daniele, M. A., & Walper, S. A. (2017). Affinity purification of bacterial outer membrane vesicles (OMVs) utilizing a His-tag mutant. Research in microbiology, 168(2), 139-146. http://hdl.handle.net/1805/14162
Alves, N. J., Turner, K. B., Medintz, I. L., & Walper, S. A. (2016). Protecting enzymatic function through directed packaging into bacterial outer membrane vesicles. Scientific reports, 6, 24866. http://hdl.handle.net/1805/18692
Stubblefield, W. B., Alves, N. J., Rondina, M. T., & Kline, J. A. (2016). Variable Resistance to Plasminogen Activator Initiated Fibrinolysis for Intermediate-Risk Pulmonary Embolism. PLOS ONE, 11(2), e0148747. http://hdl.handle.net/1805/9135
Alves, N. J., Turner, K. B., & Walper, S. A. (2016). Directed protein packaging within outer membrane vesicles from Escherichia coli: Design, production and purification. JoVE (Journal of Visualized Experiments), (117), e54458-e54458. http://hdl.handle.net/1805/14163
Alves, N. J., Turner, K. B., Medintz, I. L., & Walper, S. A. (2015). Emerging therapeutic delivery capabilities and challenges utilizing enzyme/protein packaged bacterial vesicles. Therapeutic delivery, 6(7), 873-887. http://hdl.handle.net/1805/18693
Beam, D. M., Neto-Neves, E. M., Stubblefield, W. B., Alves, N. J., Tune, J. D., & Kline, J. A. (2015). Comparison of Isoflurane and α-Chloralose in an Anesthetized Swine Model of Acute Pulmonary Embolism Producing Right Ventricular Dysfunction. Comparative Medicine, 65(1), 54–61. http://hdl.handle.net/1805/10356
Handlogten, M. W., Kiziltepe, T., Alves, N. J., & Bilgicer, B. (2012). Synthetic allergen design reveals the significance of moderate affinity epitopes in mast cell degranulation. ACS chemical biology, 7(11), 1796-1801. http://hdl.handle.net/1805/18694
Kiziltepe, T., Ashley, J. D., Stefanick, J. F., Qi, Y. M., Alves, N. J., Handlogten, M. W., ... & Bilgicer, B. (2012). Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo. Blood cancer journal, 2(4), e64. http://hdl.handle.net/1805/18695