Shanta Messerli, PhD

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder in which patients often develop multiple lesions, including slow growing spinal cord schwannomas and cutaneous schwannomas in the periphery, and meningiomas and gliomas in the brain and spine. Although usually benign and focal schwannomas and meningiomas associated with NF2 can severely compromise neural function leading to paralysis, deafness, and death through compression of critical brain nerves and structures, or blockade of CSF flow. In NF2, the most severe and life-threatening tumors are cranial nerve schwannomas and meningiomas at the skull base, which due to their size or multiplicity, are not surgically accessible. Repeated resection of tumor material can leave patients with multiple neurologic deficits, further loss of nerve function, and so debilitated that further surgery is not helpful. We have developed mouse models of NF2, and have been investigating the effect of a number of therapeutics on growth of tumors in these models. It is our hope to find a novel pharmacological compound which effectively reduces tumor growth as an alternative to surgery.

Relevant Publications:

Messerli, S. M., Tang, Y., Giovannini, M., Bronson, R. T., Weissleder. R. & Breakefield, X. O. (2002). Detection of spontaneous schwannomas by MRI in a transgenic murine model of neurofibromatosis type 2. Neoplasia, 4 (6): 501-509.

Messerli, S. M., Prabhakar, S., Tang, Y., Shah, K., Cortes, M. L., Murthy, V., Weissleder, R., Breakefield, X. O., & Tung, C. (2004). A novel method for apoptosis imaging an ICE (caspase-1)-near infrared fluorescent imaging probe. Neoplasia, 6 (2): 1-11.

Stemmer-Rachamimov, A., Louis, D. N., Nielsen, G. P., Antonescu, C., Borowsky, A., Bronson, R., Burns, D.K., Cervera, P., McLaughlin, M., Reifenberger, G., Schmale, M., MacCollin, M., Chao, R., Cichowski, K., Kalamarides, M., Messerli, S. M., McClatchey, A., Niwa-Kawakita, M., Ratner, N., Reilly, K., Zhu, Y. & Giovannini , M. (2004). Comparative pathology of nerve sheath tumors in mouse models and humans. Cancer Research, 64 (10), 3718-3724.

Messerli, S. M., Prabhakar, S., Tang, Y., Maymood, U., Giovannini, M., Weissleder, R., Bronson, R., Martuza, R., Rabkin, S., & Breakefield, X. O. (2006). Treatment of schwannomas with an oncolytic HSV recombinant virus in murine models of neurofibromatosis type 2. Human Gene Therapy, 17: 1-11.

Prabhakar, S., Messerli, S. M., Stemmer-Rachmimov, A., Liu, T., Samuel Rabkin, S., Martuza, R., and Breakefield, X. O. (2007). Treatment of implantable NF2 schwannoma tumor models with oncolytic herpes simplex virus G47Δ. Cancer Gene Therapy, 1-8.

Demestre, M., Messerli, S. M., Celli, N., Shahhossini, M., Kluwe, L., Mautner, V., & Maruta, H. (2009). CAPE (Caffeic Acid Phenethyl Ester)-based propolis extract (Bio-30) suppresses the growth of human neurofibromatosis (NF) tumor xenografts in mice. Phytotherapy Research, Feb; 23(2): 226-30.

Messerli, S. M., Ahn, M-R., Kunimasa, K., Yanagihara, M., Tatefuji, T., Hashimoto, K., Mautner, V., Uto, Y., Hori, H., Kumazawa, S., Kaji, K., Ohta, T., & Maruta, H. (2009). Artepillin C (ARC) in Brazilian Green Propolis selectively blocks the oncogenic PAK1 signaling and suppresses the growth of NF tumors in mice. Phytotherapy Research, Mar; 23(3): 423-7.

Hashimoto, H.,, Messerli, S. M., Sudo, T.,& Maruta, H. (2009). Ivermectin Inactivates the Kinase PAK1 and Blocks the PAK1-dependent Growth of Human Ovarian Cancer and NF2 Tumor Cell Lines. Drug Discovery and Therapeutics, 3(6): 243-6.

Prabhakar, S., Brenner, G. J, Sung, B., Messerli, S. M., Mao, J., Sena-Esteves, M., Stemmer-Rachamimov, A., Tannous, B., and Breakefield, X.O. (2010). Imaging and therapy of experimental schwannomas using HSV amplicon vector encoding apoptotic protein under Schwann cell promoter. Cancer Gene Therapy, Apr; 17(4): 266-74.

Maruta, H. & Messerli, S. M.: Development of new anti-cancer drugs that block the kinase PAK1. Frontiers in Drug Design and Discovery, Bentham Books, pp.121-46, 2010