The general area of my research is the application of biotechnology to solve medical problems. Toward this end, my research group has developed significant expertise in the engineering, expression, and purification of recombinant proteins produced in Escherichia coli bacteria. We developed the NusA fusion protein system for expressing recombinant proteins in soluble form, which has been licensed by the University of Oklahoma to a biotechnology company for the worldwide research market.
The primary emphasis of current research has been on the development of targeted therapies using several approaches:
· We are targeting enzymes to tumors for a process called enzyme prodrug therapy. Once bound to the tumor, the enzyme converts a nontoxic drug to a toxic cancer drug. This type of therapy has the advantage of greatly reducing the often severe side effects caused by the systemic administration of cancer drugs.
· Conjugates of recombinant proteins and single-walled carbon nanotubes (SWNTs) are targeted to tumors in combination with checkpoint inhibitor antibodies to stimulate the immune system. SWNTs are unique in that they strongly absorb near-infrared (NIR) light, while biological systems have very low levels of absorption of NIR light. The targeting of SWNTs to tumors and subsequent application of NIR light allows the selective elimination of tumors.
· Protein-drug conjugates are targeted to tumors and bacteria. For treating infectious diseases such as E. coli and L. monocytogenes, we demonstrated an increase in the effectiveness of antibiotics by as much as four orders of magnitude compared to the free antibiotics.
Textbook Web Site
Bioseparations Science and Engineering Textbook second edition
“Targeted Single-Walled Carbon Nanotubes for Photothermal Therapy Combined with Immune Checkpoint Inhibition for the Treatment of Metastatic Breast Cancer,” (with P. McKernan, N.A. Virani, G. Faria, C. Karch, R. Prada Silvy, and D.E. Resasco), Nanoscale Research Letters, 16 (2021).
“Anionic Phospholipid Expression as a Molecular Target in Listeria monocytogenes and Escherichia coli,” P. McKernan, B. Cassidy, A. Woodward, J. Battiste, and D. Drevets, International Journal of Antimicrobial Agents, 56, 106183 (2020).
“Anti-CD73 and Anti-OX40 Immunotherapy Coupled with a Novel Biocompatible Enzyme Prodrug System for the Treatment of Recurrent, Metastatic Ovarian Cancer,” (with N.V. Virani, E. Thavathiru, P. McKernan, K. Moore, and D.M. Benbrook), Cancer Letters, 425: 174-182 (2018).
“Phosphatidylserine Targeted Single-Walled Carbon Nanotubes for Photothermal Ablation of Bladder Cancer,” (with N.A. Virani, C. Davis, P. McKernan, P. Hauser, R.E. Hurst, J. Slaton, R.P. Silvy, and D.E. Resasco), Nanotechnology, 29: 035101 (2018.).
“Antitumor Synergism and Enhanced Survival in Immune-Competent Mice Treated with a Vascular-Targeted Enzyme Prodrug System, Rapamycin, and Cyclophosphamide,” (with J.J. Krais, J.J., N. Virani, P.H. McKernan, Q. Nguyen, L.M. Fung, V.I. Sikavitsas, V.I., and C. Kurkjian), Molecular Cancer Therapeutics, 16: 1855 (2017).
“Annexin-Directed β-Glucuronidase for the Targeted Treatment of Solid Tumors,” (with K.P. Guillen, E.A. Ruben, and N. Virani), Protein Engineering, Design and Selection, 30: 85 (2017)
Bioseparations Science and Engineering, (with P. Todd, P., S.R. Rudge, and D.P. Petrides), 2nd ed., Oxford University Press, New York (2015).
“Annexin V-Directed Enzyme Prodrug Therapy plus Docetaxel for the Targeted Treatment of Pancreatic Cancer,” (with K.P. Guillen, A. Restuccia, and C. Kurkjian), Pancreas, 44: 945 (2015).
“Targeted Enzyme Prodrug Therapy for Metastatic Prostate Cancer – A Comparative Study of L-Methioninase, Purine Nucleoside Phosphorylase, and Cytosine Deaminase,Guillen,” (with K.P. Guillen and C. Kurkjian), J. Biomedical Science, 21, 65 (2014).
“Bioseparation Basics,” Chemical Engineering Progress, 110, 36 (2014).
“Targeting Single-Walled Carbon Nanotubes for the Treatment of Breast Cancer Using Photothermal Therapy,”Neves, (with L.F.F. Neves, J.J. Krais, B.D. Van Rite, R. Ramesh, and D.E. Resasco), Nanotechnology, 24, 375104 (2013).
“Antitumor Activity of an Enzyme Prodrug Therapy Targeted to the Breast Tumor Vasculature,” (with B.D. Van Rite, J.J. Krais, M. Cherry, V.I. Sikavitsas, and C. Kurkjian), Cancer Investigation, 31, 505 (2013).
“Purine Nucleoside Phosphorylase Targeted by Annexin V to Breast Cancer,” (with J.J. Krais), PLOS ONE, 8, e76403 (2013).
“Enzyme Prodrug Therapy Designed to Target L-Methioninase to the Tumor Vasculature,” (with B.D. Van Rite, Y.A. Lazrak, M.L. Pagnon, N.R. Palwai, L.F. Neves, P.S. McFetridge), “ Cancer Letters, 301, 177 (2011).
“Annexin V-targeted Enzyme Prodrug therapy Using Cytosine Deaminase in Combination with 5-Fluorocytosine,” (with B.D. Van Rite), Cancer Letters, 307, 53 (2011).
“Vascular Targeted Carbon Nanotubes for Near-infrared Light Therapy of Cancer,” (with W.M. Prickett, B.D. Van Rite, and D.E. Resasco), Nanotechnology, 22, 455101 (2011).
“Prediction of Protein Solubility in Escherichia coli using Logistic Regression,” (with A.A. Diaz, E. Tomba, R. Lennarson,R. Richard, M.J. Bagajewicz), Biotechnol. Bioeng., 105, 374 (2010).