DONALD S. SAKAGUCHI

Ph.D. State University of New York, Albany, 1984
Associate Professor, Department of Genetics, Development and Cell Biology (GDCB))
College of Liberal Arts and Sciences and College of Agriculture
Adjunct Associate Professor, Department of Biomedical Sciences, College of Veterinary Medicine

e-mail DSSAKAGU@IASTATE.EDU

Fields of Interest: Developmental neurobiology, stem cells, development and regeneration of vertebrate visual systems, glaucoma and other retinal diseases, cellular and molecular basis of neuron/glial cell interactions.

Program Affiliations: Neuroscience Program, Molecular, Cellular, and Developmental Biology Program (MCDB), Bioinformatics and Computational Biology (BCB), Complex Adaptive Systems Group (CAS), and the Institute of Science and Society

Check out the Sakaguchi Lab Homepage.

1. Stem cell biology: Transplants of neural stem cells to study development and plasticity:
In the mammalian central nervous system (CNS) the death of neurons is a devastating consequence of neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, or secondarily from stroke or head and spinal cord trauma. Furthermore, retinal degenerative diseases result in blindness or impaired vision in hundreds of thousands of individuals each year. Until recently, it was believed that the mature mammalian brain lacks the capacity for self-renewal and this is, in part, was explained by the inability of the mature CNS to generate significant new cellular components in response to damage or disease. Neural stem cell transplantation offers a novel and extremely exciting possibility to circumvent this limitation.
The retina is an ideal CNS structure for investigation of neural stem cell function. It is a highly organized CNS structure that is easily accessible for experimental manipulation. All vertebrate retinas are organized in the same fashion and the five neuronal cell types can be reliably identified based on their position and morphology within the retina.
In this series of projects we are investigating the capacity for neural stem cells and adult bone marrow derived stem cells transplanted into the eye to survive, differentiate, and integrate into the host retina. We are investigating how the host environment influences the survival, differentiation, and integration of stem cells? For these studies we are taking advantage of a unique in vivo experimental model system, the Brazilian opossum, Monodelphis domestica. We are among the first to have established the Brazilian opossum as a new experimental model for studies of mammalian visual system development. Monodelphis pups are born after 14 days gestation in an extremely immature, fetal-like state. We discovered that the majority of neurogenesis in the retina occurs postnatally, and that the axons of the ganglion cells do not reach their central targets until approximately five days after birth. In contrast, in other mammalian model systems (including mice, rats, ferrets, cats and primates) a major portion of these events occur during fetal development. Thus, Monodelphis provides an attractive new system for in vitro, as well as in vivo, studies for investigating the development and plasticity of the mammalian visual system. In addition, we are also using/developing models of retinal damage to investigate the potential use of stem cell transplants as a strategy for CNS rescue and repair.

2. Experimental strategies for CNS rescue and repair:
Many diseases of the central nervous system (CNS) are characterized by the devastating loss of neurons, including blinding diseases of the eye. For example, the permanent loss of retinal ganglion cells (RGCs) is a hallmark of many ophthalmic diseases including glaucoma. Recent estimates suggest that at least 3 million Americans are afflicted with glaucoma. As a potential therapy for treatment of neurodegenerative diseases, neural stem/progenitor cells (NSCs) have recently been proposed as a unique source of transplantable cells to replace degenerating neurons and glia in the CNS. We are using this strategy and evaluate the survival, differentiation and integration of neural stem/progenitor cells transplanted into the damaged retina using rodent models of glaucoma. Our working hypothesis is that neural stem cells can replace lost neurons and restore visual function in the glaucomatous retina. As an additional strategy we are injecting biodegradeable polymer microspheres engineered to slowly release neurotrophic growth factors into the injured eye. Sustained slow release of these factors may provide a neuroprotective influence within the damged tissue.

3. Retinal development: Cellular interactions:
The aim of this project is to help us gain a better understanding of the cellular and molecular basis of vertebrate retinal development. Before the onset of visual function, spontaneous activity is present in the developing mammalian retina. This spontaneous, correlated activity is essential for the normal development of the visual system. It is likely that cholinergic amacrine cells are required for the propagation of this spontaneous activity and therefore, these cells mediate early events crucial to the establishment of proper retinal circuitry, and therefore would influence further development of the mammalian visual system. The specificity and timecourse of expression of high levels of SNAP-25 in cholinergic amacrine cells provides evidence that this presynaptic terminal-associated protein plays an integral role in mediating the transient function provided by these amacrine cells during this early "critical period" of development. In this project we are investigating the role of cholinergic amacrine cells during the development of the laminar organization of the mammalian retina.

Publications, Teaching, and Undergraduate Internship Opportunities:

Sakaguchi Lab Publications: Titles and Abstracts (pdf versions of some journal articles available).

Don Sakaguchi's Teaching Interests
Biology 394 (section HN): Marine Biology: Field Trip.

Visit the: Sakaguchi Lab.

Club Retina meets Wed. at 4:00 PM in 502 Science II during the summer semester.

Neuro 690 Journal Club meets Thursday's at 3:45 PM during the fall semester.

Seminars of Interest to the ISU Neuroscience Community

Cells and Materials: At the Interface between Mathematics, Biology and Engineering
Workshop III: Angiogenesis, NeoVascularization and Morphogenesis
May 8 - 12, 2006
http://www.ipam.ucla.edu/programs/cmws3/

Western Eye Research Conference (WERC), Laguna Beach, CA; September 25-28, 2005

Advanced Retinal Therapy: Update-Trends-Controversies; Vienna, Austria: November 27, 2004

2004 Symposium - "Stem Cell Biology: Development and Plasticity"
September 16-19, 2004 Iowa State University.
Proceedings to be published in the Annals of the New York Academy of Sciences (2005)

26th Midwest Neurobiology Meeting: Location to be announced.
25th Midwest Neurobiology Meeting, University of Illinois, Chicago: held May 21-23, 2004
24th Midwest Neurobiology Meeting: Iowa State University, Ames, IA: held May 16-18, 2003.

April 16-20, 2001
University of Coimbra, Portugal
Workshop on: "Development and Plasticity of the Vertebrate Retina and Visual Pathway"

Coordinator: C. Duarte, Dept. Zoology, Univ. of Coimbra, Portugal; Instructors: D. Sakaguchi, Neuroscience Program, Iowa State Univ. and M. Young, Schepens Eye Research Institute, Harvard Med. Sch.

Check out the Sakaguchi Lab Homepage or visit the Department of Genetics, Development and Cell Biology or the Neuroscience Program homepage.

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Last updated: 08/2008