Andrew G. Maselli, Ph.D.
Department of Biological Sciences
As the human population ages, neurodegenerative diseases have become a major health
concern. Substantial progress has been made, but the underlying causes of these diseases
are complex and poorly understood. One of the least understood structural manifestations
of neurodegenerative disorders are Hirano bodies. Hirano bodies are actin-based inclusions,
which have been identified in the brains of individuals with a broad range of neurodegenerative
disorders including Alzheimer’s disease. The contribution of Hirano bodies to neurodegeneration
is a mystery. It is unclear if Hirano bodies are the causative agents of the pathology
observed or a morphological marker for other changes occurring as part of the degenerative
To understand the process that triggers the formation of Hirano bodies it is necessary
to have a model system in which the molecular mechanisms for the formation of Hirano
bodies can be characterized in living cells. We have shown that the expression of
a truncated 34 kDa actin binding protein with uncontrolled actin cross-linking activity
can induce the formation of Hirano bodies in the eukaryotic model systemDictyostelium
discoideum (Maselli et al., 2003; Maselli et al., 2002). The model Hirano bodies
formed inDictyostelium have ultrastructural and biochemical characteristics that are
similar to that of human Hirano bodies (Maselli et al., 2002). Our hypothesis is
that when small amounts of an uncontrolled actin crosslinker are present in the cell,
a cascade of events begins which leads to Hirano body formation. Preliminary data
suggests that a fragment of the actin binding protein fimbrin initiates actin inclusion
formation. This is an exciting development becauseDictyostelium fimbrin is a clear
homology to human plastin. The ultimate goal is to understand the connection between
actin binding protein fragments and human Hirano bodies. One of the logical sources
for these actin binding protein fragments in brain cells is from the cell's own proteins
that have been cleaved by proteases. We propose to investigate the cascade of events
leading the Hirano body formation and identify candidate truncated actin binding proteins
usingDictyostelium as a model system
This project provides a number of excellent opportunities for student undergraduate
and graduate. Our laboratory uses a broad range of molecular biology, cell biology
and microscopy techniques. The generous support of the MBRS program has provided
state of the art research equipment, which, is available for student driven research.
Helping students develop as independent scientists and make significant contributions
to this research project is a core mission of the laboratory.
Dr. Maselli (2nd from the left) with colleagues and students.
Maselli, A., Thomson, S. A. M., Davis, R., Furukawa, R., and Fechheimer, M. (2003) “Formation
of Hirano Bodies Induced by Expression of a Modified Form of an Actin Cross-linking
Protein with Point Mutations that Activate Actin Binding.”Eukaryotic Cell 4:778-787.
Furukawa, R., Maselli, A., Thomson S. A. M., Lim. R.W., and Fechheimer M. (2003) “Calcium Regulation of Actin
Cross-linking Is Important for Function of the Actin Cytoskeleton inDictyostelium.”Journal
of Cell Science 116: 187-196.
Fechheimer, M., Furukawa, R., Maselli A., and Davis R. (2002) “Hirano Bodies in Health and Disease”Trends in Molecular Medicine
Maselli, A.G., Davis, R., Furukawa, R., Fechheimer M. (2002). “Formation of Hirano Bodies in
Dictyostelium and Mammalian Cells Induced by Expression of a Modified form of an Actin-crosslinking
Protein.”Journal of Cell Science 115:1939-49.
Maselli, A., Laevsky, G., Knecht, D. (2002). “Kinetics of Binding, Uptake and Degradation of
Live Fluorescent (DsRed) Bacteria byDictyostelium discoideum.” Microbiology 148:413-20.
(RISE students are indicated in boldface.)
Camargo, M, Maselli, A. (2007) Expression of Human T-plastin inDictyostelium discoideum
The American Society of Cell Biology 47th annual meeting.
J. Ramos*, M. Myrthil, K. Stone, and A. Maselli (2006) Comparison Of Hirano Body Formation Initiated By
An F-Actin Stabilizing Drug And A Truncated Actin Bundling Protein, Illinois State
Academy of Science 99th annual meeting. Springfield, IL. (Presented by J. Ramos)
J. Ramos, A. Maselli (2006). Exploring Drug Stabilized F-actin as a Live Cell Model
for Hirano Body Formation. The American Society of Cell Biology 46th annual meeting.
(Presendted by J. Ramos)
Ran-Der Hawag, Chin-Chi Chen, Raymond Washington, Andrew G. Maselli and David A. Knceht
(2006). Regulation of Actin Cytoskeletal Architecture by Fimbrin A. International
Dictyostelium Conference, Santa Fe, NM. (Presented by Ran-Der Hwang)
Vashati Butler, Marsha Myrthil, and Andrew Maselli, Hirano Bodies Are Found In The Cytoplasmic Bridge Between Dividing
Dictystelium Cells, 9th Annual Illinois LS-AMP Student Research Conference, Glenview,
Illinois, October 6-7, 2006.
J. F. Reyes, A. G. Maselli (2005) The Formation of GFP-Tagged Hirano Bodies inDictyostelium
discoideumafter Inducible Expression of a Truncated Actin BundlingProtein , American
Society of Cell Biology 45th annual meeting.
J. F. Reyes and A. G. Maselli (2005).Studying the formation of Hirano Bodies in Dictyostelium
discoideum in vivo using vectors with inducible promoters, Illinois State Academy
of Science 97th Annual meeting. Galesburg, IL.
R. Furukawa, L. F. Hoagland, R. C. Davis, A. G. Maselli, M. Fechheimer (2004) ;Myosin
II Is Required for Hirano Body Formation. 44st American Society for Cell Biology
Annual Meeting, Washington, D.C.
Dr. Andrew Maselli (far left) and his research team, 2006.
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