Steve Swenson, PhD

My main area of scientific interest lies in the development of novel direct acting protein based drugs to be utilized in the fight against disease. This interest has been addressed and will continue to be pursued through three distinct but related studies:
The development of novel protein based agents, understanding their mechanism of action and effect on disease
The delivery and efficient targeting of protein based therapeutics characterizing their biochemical and biophysical properties.
Modification of proteinsand gaining an understanding of their action for use as diagnostic and imaging agents in determination of disease progression.
My future research plans in the near term involve continued development of the snake venom disintegrin CN as a clinically applicable therapeutic agent both in collaboration with the Markland laboratory and as an independent investigator. In one study, we plan to biochemically, biophysically and biologically evaluate a recombinant version of contortrostatin (rCN) under production in Dr. Marklands laboratory. In addition to the rCN characterization development of assays to assure rCN batch-to-batch production quality and homogeneity are under way.

It has been observed that binding of CN to integrins produces an effect on a number of cellular processes including cell migration and cell cycle progression. However, the mechanism behind these effects is unknown. Elucidation of the effect of CN on signaling pathways within a cell will enhance our knowledge about cellular processes and may allow for the development of more effective anticancer therapy. In addition to delving into a mechanistic understanding of CN, I am focused on the development of disintegrin based imaging agents which will aid in diagnostics and evaluation of metastatic disease. These studies are possible because CN accumulates at the site of a tumor. By employing PET imaging (Positron Emission Tomography) of a radio-labeled CN in conjunction with 18Ffluorodeoxyglucose (18FDG) utilization, It is planned that an agent will be developed that is capable of identifying and evaluating metastatic tumor foci. Along these same lines I plan to develop a brachytherapeutic to be used in gliomas. CN or other similar proteins can be labeled with a radionuclide such as 131I and administered intrathecally. To act directly on the growing gliomas.

An additional project will involve screening venoms from different snake families and species to determine the protein composition of the venom (a snake venom proteomics project) in collaboration with Dr. Austin Yang of the USC School of Pharmacy who is interested in such a project. This screening will allow me to identify possible candidate proteins for development into therapeutic agents. All venom is different and understanding what is actually present and what can be used would be a great leap in understanding the biochemistry of venom proteins.

• Inhibition of autophagy and induction of glioblastoma cell death by NEO214, a perillyl alcohol-rolipram conjugate Autophagy. 2023 12; 19(12):3169-3188. . View in PubMed
• Neuro Oncol. 2021 01 30; 23(1):63-75. . View in PubMed
• Preclinical studies of a novel snake venom-derived recombinant disintegrin with antitumor activity: A review Biochem Pharmacol. 2020 11; 181:114149. . View in PubMed
• Methods for Evaluation of a Snake Venom-Derived Disintegrin in Animal Models of Human Cancer Methods Mol Biol. 2020; 2068:185-204. . View in PubMed
• Developing a clinically relevant radiosensitizer for temozolomide-resistant gliomas PLoS One. 2020; 15(9):e0238238. . View in PubMed
• Inhibition of motility by NEO100 through the calpain-1/RhoA pathway J Neurosurg. 2019 Aug 16; 1-12. . View in PubMed
• The Rolipram-Perillyl Alcohol Conjugate (NEO214) Is A Mediator of Cell Death through the Death Receptor Pathway Mol Cancer Ther. 2019 03; 18(3):517-530. . View in PubMed
• A Novel Venom-Derived Peptide for Brachytherapy of Glioblastoma: Preclinical Studies in Mice Molecules. 2018 Nov 08; 23(11). . View in PubMed
• NEO212 Inhibits Migration and Invasion of Glioma Stem Cells Mol Cancer Ther. 2018 03; 17(3):625-637. . View in PubMed
• Multimeric disintegrin protein polymer fusions that target tumor vasculature Biomacromolecules. 2014 Jul 14; 15(7):2347-58. . View in PubMed
• Snake venom metalloproteinases Toxicon. 2013 Feb; 62:3-18. . View in PubMed
• Development of a chimeric recombinant disintegrin as a cost-effective anti-cancer agent with promising translational potential Toxicon. 2012 Mar 15; 59(4):472-86. . View in PubMed
• Contortrostatin, a homodimeric disintegrin isolated from snake venom inhibits herpes simplex virus entry and cell fusion Antivir Ther. 2012; 17(7):1319-26. . View in PubMed
• The disintegrin contortrostatin in combination with docetaxel is a potent inhibitor of prostate cancer in vitro and in vivo Prostate. 2010 Sep 01; 70(12):1359-70. . View in PubMed
• Vicrostatin – an anti-invasive multi-integrin targeting chimeric disintegrin with tumor anti-angiogenic and pro-apoptotic activities PLoS One. 2010 Jun 03; 5(6):e10929. . View in PubMed
• The use of pepsin in receptor internalization assays Biochem Biophys Res Commun. 2009 Oct 16; 388(2):240-6. . View in PubMed
• Integrin agonists as adjuvants in chemotherapy for melanoma Clin Cancer Res. 2008 Oct 01; 14(19):6193-7. . View in PubMed
• Structure of acostatin, a dimeric disintegrin from Southern copperhead (Agkistrodon contortrix contortrix), at 17 A resolution. Acta Crystallogr D Biol Crystallogr. 2008 Apr; 64(Pt 4):466-70. . View in PubMed
• Anti-angiogenesis and RGD-containing snake venom disintegrins Curr Pharm Des. 2007; 13(28):2860-71. . View in PubMed
• Contortrostatin, a snake venom disintegrin with anti-angiogenic and anti-tumor activity Pathophysiol Haemost Thromb. 2005; 34(4-5):169-76. . View in PubMed
• Development of a novel recombinant disintegrin, contortrostatin, as an effective anti-tumor and anti-angiogenic agent Pathophysiol Haemost Thromb. 2005; 34(4-5):177-83. . View in PubMed
• Intravenous liposomal delivery of the snake venom disintegrin contortrostatin limits breast cancer progression Mol Cancer Ther. 2004 Apr; 3(4):499-511. . View in PubMed
• Molecular cloning and functional expression of contortrostatin, a homodimeric disintegrin from southern copperhead snake venom Arch Biochem Biophys. 2000 Mar 15; 375(2):278-88. . View in PubMed
• Contortrostatin, a homodimeric disintegrin, binds to integrin alphavbeta5 Biochem Biophys Res Commun. 2000 Jan 07; 267(1):350-5. . View in PubMed

• Chen, Thomas
• Minea, Radu
• Matsuo, Koji
• Zlokovic, Berislav
• Lenz, Heinz-Josef