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Investigators and Program Directors

Anne Messer

Anne Messer

Research Scientist, Wadsworth Center, Molecular Genetics
Professor, School of Public Health, Biomedical Sciences

Ph.D., University of Oregon
Postdoctoral training, Harvard Medical School

Intrabody treatment reduces aggregate number and size in the striatum of HDR6/1 mice

Cells in the transduced striatal
region (right) show dramatically
fewer aggregates overall than
uninjected regions (left), even
at 13 weeks.

HDR6/1 mouse injected with
AAV2/1-scFv -C4 at 8wks;
sacrificed at 13 wks. 40X
Anti-htt EM48 (red).

Research Interests

My neurogenetics laboratory is involved in both genomics and gene therapy projects. We have over 25 years of experience experimenting with mouse models and neuronal cell cultures as models of disorders of neuronal development and neurodegeneration. Our studies have contributed to the literature on autism, hypothyroidism, Batten Disease, motor neuron disease (ALS), Huntingtonís Disease, and Parkinsonís Disease, as well as more basic mechanisms of cell signaling during brain development. Over the past 10 years, a major goal has been to develop gene and antibody therapies for neurodegenerative diseases caused by abnormal protein accumulation. We pioneered using engineered intracellular antibody fragments (intrabodies) to specifically re-fold or retarget pathogenic proteins in neurons, collaborating with protein and antibody engineering laboratories, and cross-training a number of students and postdocs.

Current Projects:

Huntington’s Disease: Single-chain Fv (scFv) intrabodies appear effective against Huntington’s Disease in vitro and in vivo; and we are refining gene and protein delivery, plus combinatorial therapies. Complementary HD research in the lab studies the involvement of DNA repair in the underlying mechanisms of repeat instability, other genetic background effects on disease onset and progression, and active immunizations.

Parkinson’s Disease: We are currently testing four candidate anti-alpha-synuclein intrabodies for Parkinson's Disease using cell cultures. These should be going into preclinical trials using transgenic mice and gene delivery vectors in mouse brain shortly. In order to increase stability of these antibody fragments as intrabodies, we are also examining variable heavy-chain (VHH) camelid candidates.

Conformation-specific intrabodies: In collaboration with Dr. Michael Sierks, Arizona State Univ, we are utilizing scFvs that recognize specific misfolded states of neurodegenerative proteins, both as research tools and as potential therapeutics.

Macular Degeneration: We have generated an immune camelid nanobody library to proteins that are overexpressed in drusen. Testing includes collaboration with Dr. Sally Temple of the Neural Stem Cell Institute.

Collaborative virology projects: Studies on West Nile Virus, and the interaction of chaperones common to Herpes Virus replication and misfolding neuronal proteins, are in the early stages.

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