RESEARCH INTERESTS:

Dr. Messerli’s principal research interests involve examining the signaling mechanisms involved with neuronal injury and repair. This involves studying chemical toxicity and mechanical damage to neurons, possible therapies for neuronal tumors, as well as mechanisms of resistance of tumors to chemotherapeutic drugs.  The research program focuses on the development of both effective gene therapy and signal blocking therapeutics to treat a variety of tumors whose growth depends on the kinase PAK1, including those associated with neurofibromatosis type 2 (NF2), gliomas, prostate tumors, and pancreatic cancers. In addition, the laboratory is examining the role of multidrug resistance (MDR) transporters in the development of resistance to chemotherapeutic drugs.  A better understanding of the molecular and cellular mechanisms underlying neuronal injury and repair will provide insight into the development of new therapies for neurological diseases.

Current research is investigating the use of anti-cancer therapeutics to treat tumors found in mouse models of neurofibromatosis type 2 (NF2) and neurofibromatosis type I (NF1).  NF2 is an autosomal dominant disorder in which patients develop multiple lesions, including meningiomas and gliomas in the brain, and schwannomas, benign tumors of the peripheral nerve sheath, which damage nerves by compression.  NF1 is also an autosomal dominantly inherited disorder and is characterized by developmental changes in the nervous system, skin, bones, and other tissues. Its most distinctive features are multiple benign, soft tumors called neurofibromas and patches of skin pigmentation called café-au-lait  spots.  NF1 can also affect nerves throughout the body, including in the brain and spinal cord.

Gene therapy and /or novel NF therapeutics, may prove to be a complementary strategy to use of chemotherapeutic drugs and neurosurgery for treating these tumors due to the inability of many typical chemotherapeutic drugs to get past the blood brain barrier and the risk of nerve damage with surgery.  Our objective is to develop an effective strategy, either using a targeted gene delivery system and/ or by use of a novel anti-cancer therapeutic, which is capable of crossing the blood brain barrier, to reduce growth tumor growth, both in vitro and in NF2 murine models.  This work will provide valuable insight into the use of targeted viral vectors and / or novel anti-cancer therapeutics to treat tumors from many forms of cancer.  Our broader interests include development and testing of targeted therapies for treatment of a variety of cancers.

*Immortalized human schwannoma HEI-193 cells (House Ear Institute) from a Neurofibromatosis Type 2 (NF2) patient (Hung et al., 1993) imaged with orientation independent differential interference contrast microscopy.    These phase contrast images were taken with a 100 x objective (0.3 NA).  Scale bar = 10 microns. 

(Imaged by Michael Shribak and Shanta Messerli)

Supported by Merrimack Pharmaceuticals, Peterson Foundation, NF CURE, Neurofibromatosis Inc., Yamada Bee Farm, Department of Defense (DOD), NIH, and NSF.