CBE Seminar: Kaushal Rege, Arizona State University
"Aminoglycoside-derived Molecular and Cellular Technologies for Accelerated Discovery Platforms"
Innovations in molecular and cellular technology platforms can engender rapid discoveries in biotechnology and medicine. Research in my laboratory synergizes the use of combinatorial synthesis, chemical informatics, and cell-based screening for developing new platforms that facilitate the accelerated discovery of materials and therapeutics. In recent years, we have exploited the exquisite chemical diversity of aminoglycosides, traditionally used as antibacterial drugs, for generating soluble polymers, nanoparticles, microbeads, and hydrogels as enabling platform technologies. In the first part of this presentation, I will discuss our work on combinatorial libraries of soluble polymers and nanoparticles as carriers of small-molecule drug and nucleic acids. Parallel screening and chemical informatics analyses led to molecular-level insights into structural and chemical factors influencing polymer-mediated transgene expression. Along with carrier discovery, we used parallel screens for also identifying kinase and epigenetics modulators whose inhibition led to enhanced transgene expression in cells. This synergistic approach of combining accelerated materials discovery, chemical informatics, and molecular screens has led to novel delivery vehicles, combination treatments, and greater understanding of cellular barriers that enhance transient protein production. In the second part, I will present our work on aminoglycoside-derived hydrogels and their application in the formation of three-dimensional (3D) microenvironments of cancer and stem cells. Microenvironments of bladder and breast cancer cells were arrested in the G0/G1 phase of the cell cycle and were resistant to conventional anti-proliferative drugs, indicating dormancy. Therapeutic interventions modulating the protein production machinery in cells, resulted in chronic endoplasmic reticulum (ER) stress and concomitant ablation of these 3D dormant tumor microenvironments (3D-DTMs). The 3D-DTM platform has helped advance our understanding of chemo-mechanical and biochemical factors involved in cancer dormancy and escape, and facilitated the identification of new therapeutic interventions for the ablation of dormant cancer cells. Taken together, our results demonstrate that aminoglycoside-derived molecular and cellular platforms can accelerate molecular discovery and facilitate fundamental advances in biotechnology and medicine.
BIO: Kaushal Rege is a Professor of Chemical Engineering at Arizona State University (ASU) in Tempe, A.Z. Research in Dr. Rege’s group focuses on molecular and nanoscale technologies for application in therapeutic discovery and delivery, tissue repair, and radiotherapy. Dr. Rege has published more than 80 journal papers and several book chapters. He has served as co-editor for two books and for journal special issues. He is an Associate Editor of two journals and is also an inventor of several patents and patent applications. Dr. Rege was elected to the college of fellows of the American Institute of Medical and Biological Engineers (AIMBE) in 2017. He was awarded a New Investigator Award from the American Society for Photobiology, a Young Investigator Award from the Defense Threat Reduction Agency (DTRA), and a Fulton Exemplar Faculty Award from ASU. Dr. Rege’s mentees have gone on to pursue careers in academia and industry.
Friday, April 12, 2019 at 10:00am to 11:00am
Colburn Lab, 102 CLB
University of Delaware- Colburn Lab, University of Delaware, 150 Academy St, Newark, DE 19716-3196, USA