RESEARCH PROGRAMS AND AFFILIATIONS
Brain cancer therapies; tumor microenvironment; tumor invasion; extracellular matrix; nano-therapeutics; immunotherapies
Cancer biology; cancer immunology; malignancies of the central nervous system
ASSOCIATIONS / MEMBERSHIPS
Our laboratory studies malignant brain cancers and the responses of normal cells in the brain when they interact with tumor cells. This allows us to understand how the neural microenvironment reacts to a tumor and may, in fact, help that tumor grow and disseminate.
A major area of our research is focused on the neural extracellular matrix (ECM), which is a scaffold of molecules that surround all normal cells in the brain and the malignant cells in brain cancers. We try to understand how changes in the ECM can lead to neural injury, tumor invasion, and alterations in the development of the nervous system. This research has allowed us to design reagents to target molecules in the brain microenvironment, which we are developing as diagnostic and therapeutic agents for brain cancers.
Some of the broad questions that we try to answer in our lab include:
- How do brain tumors change the structure of the ECM and the behavior of normal cells in the brain?
- Can we disrupt tumor invasion in the brain and expose the malignant cells to become more sensitive to therapies?
- Can we manipulate the neural ECM to reach brain tumor cells scattered in the brain?
- Are there mechanisms triggered by ECM proteins that make tumor cells more resistant to therapies and neural damage more persistent?
To answer these questions, our lab is fully set-up to do cellular and molecular biology, tissue analysis and pre-clinical studies. Some of the techniques that we use in the lab include: production and analysis of artificial tissue scaffolds, cultures of tissue biopsies and cell lines, intracranial surgery, viral design and transduction, time-lapse confocal microscopy, glyco-chemistry, immunochemistry, proteomics and molecular genetics.
Figure 1: Glioblastoma cells (green) migrating around a major blood vessel (red) in the brain
Figure 2: An extracellular matrix protein (green fibers) produced by glioma cells wraps around blood vessels (red) to help tumor cells scatter along capillaries.
Figure 3: Nanoparticles (green dots) designed against a protein on the surface of cancer cells. The particles are tumor-specific and do not bind to normal cells (red)
Figure 4: Novel synthetic scaffolds ("nanofibers") used to analyze the dispersion of tumor cells in vitro
Figure 5: Engineered tumor cells produce tiny fibrils on the cell surface (green) that enhance adhesion and promote metastasis
Viapiano MS, Lawler SE. Malignant glioma microenvironment. In: Youmans and Winn Neurological Surgery, 7th Ed., pp 814-824 (H. R. Winn, Ed). Elsevier, PA (2016)
Sinyuk M, Lathia JD, Viapiano MS. Characterization and analysis of extracellular matrix in malignant brain tumors and their cellular derivatives. In: Neuromethods: Extracellular Matrix, pp 113-138 (J. Leach and E. Powell, Eds). Humana Press, NJ (2015)
Sengupta S, Nandhu M, Longo S, Sengupta S, Longo J, Sampath P, Viapiano M. First-in-kind T cells carrying a chimeric antigen receptor against an extracellular matrix protein target glioblastoma cells and show anti-tumor efficacy. Neuro-Oncology (2018) 20: vi129-vi130. https://doi.org/10.1093/neuonc/noy148.542
Cho C-F, Ghotmi Y, Fadzan C, Wolfe J, Bergmann S, Qu Y, Murrell E, Bononi F, Luyt L, Chiocca EA, Viapiano M, Pentelute B, Lawler S. BTP-7, a novel peptide for therapeutic targeting of malignant brain tumors. Neuro-Oncology (2018) 20: vi74. https://doi.org/10.1093/neuonc/noy148.305
Nandhu MS, Behera P, Bhaskaran V, Longo S, Barrera-Arenas LM, Sengupta S, Rodriguez-Gil DJ, Chiocca EA, Viapiano MS. Development of a function-blocking antibody against fibulin-3 as targeted reagent for glioblastoma. Clin. Cancer Res. (2018) 24: 821-833. PMID: 29146721
Diaz F, Gregory S, Nakashima H, Viapiano MS, Knipe DM. Intramuscular delivery of replication-defective herpes simplex virus gives antigen expression in muscle syncytia and improved protection against pathogenic HSV-2 strains. Virology (2018) 513: 129-135. PMID: 29069622
Nandhu MS, Kwiatkowska A, Bhaskaran V, Hayes JL, Hu B, Viapiano MS. Tumor-derived fibulin-3 activates proinvasive NF-kappa B in glioblastoma cells and their microenvironment. Oncogene (2017) 36: 4875-4886. PMID: 28414309
Presley K, Hwang J, Cheong S, Tilley R, Collins J, Viapiano MS, Lannutti JJ. Nanoscale upconversion for oxygen sensing. Mater. Sci. Eng. C (2017) 70 (Pt 1): 76-84. PMID: 27770952
Zhao Y, Tabassum S, Piracha S, Nandhu MS, Viapiano MS, Roblyer D. Angle correction for small animal tumor imaging with spatial frequency domain imaging (SFDI). Biomed. Opt. Express. (2016) 7: 2373-2384. PMID: 27375952
Cho CF, Lee K, Speranza MC, Bononi FC, Viapiano MS, Luy LG, Weissleder R, Chiocca EA, Lee H, Lawler SE. Design of a microfluidic chip for magnetic-activated sorting of one-bead-one-compound libraries. ACS Comb. Sci. (2016) 18: 271-278. PMID: 27124678
Ropper AE, Zeng X, Haragopal H, Anderson JE, Aljuboori Z, Han I, Abd-El-Barr M, Lee HJ, Sidman RL, Snyder EY, Viapiano MS, Kim SU, Chi JH, Teng YD. Targeted Treatment of Experimental Spinal Cord Glioma With Dual Gene-Engineered Human Neural Stem Cells. Neurosurgery. (2016) 79: 481-491. PMID: 26671631
Xue R, Nelson MT, Teixeira SA, Viapiano MS, Lannutti JJ. Cancer cell aggregate hypoxia visualized in vitro via biocompatible fiber sensors. Biomaterials (2016) 76: 208-217. PMID:26524540
Xue R, Ge C, Richardson K, Palmer A, Viapiano M, Lannutti JJ. Microscale Sensing of Oxygen via Encapsulated Porphyrin Nanofibers: Effect of Indicator and Polymer "Core" Permeability. ACS Appl. Mater. Interfaces. (2015) 7: 8606-8614. PMID:25850567
Long PM, Tighe SW, Driscoll HE, Fortner KA, Viapiano MS, Jaworski DM. Acetate supplementation as a means of inducing glioblastoma stem-like cell growth arrest. J. Cell Physiol. (2015) 230: 1929-1943. PMID:25573156
Nandhu MS, Hu B, Cole SE, Erdreich-Epstein A, Rodriguez-Gil DJ, Viapiano MS. Novel paracrine modulation of Notch-DLL4 signaling by fibulin-3 promotes angiogenesis in high-grade gliomas. Cancer Res. (2014) 74:5435-5448. PMID:25139440
Roth AD, Elmer J, Harris DR, Huntley J, Palmer AF, Nelson T, Johnson JK, Xue R, Lannutti JJ, Viapiano MS. Hemoglobin regulates the migration of glioma cells along poly(ε-caprolactone)-aligned nanofibers. Biotechnol. Prog. (2014) 30: 1214-1220. PMID:25044995
Junghans A, Waltman MJ, Smith HL, Pocivavsek L, Zebda N, Birukov K, Viapiano M, Majewski J. Understanding dynamic changes in live cell adhesion with neutron reflectometry. Mod. Phys. Lett B. (2014) 28: 1430015/1 - 1430015/9. PMID:25705067
Dwyer CA, Bi WL, Viapiano MS, Matthews RT. Brevican knockdown reduces late-stage glioma tumor aggressiveness. J. Neurooncol. (2014) 120:63-72. PMID:25052349
Tsen AR, Long PM, Driscoll HE, Davies MT, Teasdale BA, Penar PL, Pendlebury WW, Spees JL, Lawler SE, Viapiano MS, Jaworski DM. Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma. Intl. J. Cancer (2014) 134: 1300-1310. PMID: 23996800
Rao SS, Lannutti JJ, Viapiano MS, Sarkar A, Winter JO. Toward 3D biomimetic models to understand the behavior of glioblastoma multiforme cells. Tissue Eng Part B Rev. (2014) 20: 314-3278. PMID: 24044776
Xue R, Behera P, Viapiano MS, Lannutti JJ. Polydimethylsiloxane-core Polycaprolactone-shell nanofibers as biocompatible, real-time oxygen sensors. Sensors and Actuators B. Chem. (2014) 192: 697-707. PMID: 25006274