Director - Aileen J. Anderson, Ph.D., Professor // Sue & Bill Gross Stem Cell Research Center // UCI

Aileen J. Anderson, Ph.D.

Professor

Biography

Dr. Anderson obtained her B.S. in Engineering at the University of Illinois Urbana-Champaign, and her Ph.D. in Biology/Neuroscience at the University of California Irvine. After post-doctoral positions at UCI and Harvard, she began her faculty position at UCI in 2001. In addition to her laboratory at UCI, a part of the CDRF International Consortium on Spinal Cord Injury and Director of the Christopher and Dana Reeve Paralysis Foundation (CDRF) Spinal Cord Injury (SCI) Research Core Facility.

Research in Lay Terms

Research in my laboratory is a combination of discovery biology and identifying translational neuroscience strategies for spinal cord injury and central nervous system disease. Pre-clinical and translational work from my laboratory has directly supported an IND filing for an FDA approved phase I trial of human neural stem cells in the myelination disorder, Pelizaeus-Merzbacher disease (PMD), and a phase I/II clinical trial for human neural stem cells in thoracic spinal cord injury (SCI), for which enrollment has recently been completed. These translational milestones reflect over fifteen years of work from my laboratory on human-derived stem cell populations and spinal cord injury mechanisms. In these studies, we have sought to investigate the intrinsic and extrinsic factors defining the migration and differentiation potential of these cells both in vitro and after transplantation into the spinal cord. In parallel, we have sought to investigate non-traditional roles for the innate inflammatory system in both the pathophysiology of spinal cord injury, mechanisms controlling stem cell fate and migration, and potential for implanted biomaterial scaffolds to provide an environment supporting robust axonal regeneration. Our recent work has demonstrated the first evidence in the field for regeneration of the corticospinal tract (CST) not only into a biomaterial bridge, but through that bridge to exit and reenter the caudal spared parenchyma; re-entry of regenerating axons in this model was associated with recovery of locomotor function.

Research Focus

Dr. Anderson’s own research is focused on two principal goals. First, investigating the interactions of transplanted stem cell populations within the injured niche, including the role of the evolving inflammatory microenvironment in stem cell fate and migration decisions. Second, investigating the role of inflammatory mechanisms in degeneration and regeneration in the injured CNS, particularly the role of the innate immune response and complement pathways in these conflicting but intertwined processes. Much of the research in Dr. Anderson’s laboratory bridges the junction between seeking to understand mechanism at the basic neuroscience level, and identifying translational neuroscience strategies to ameliorate the cellular and histopathological deficits associated with SCI to promote recovery of function.

Research Details

The processes of degeneration and regeneration are intertwined in both their impact on, and potential benefits to, the goal of improved functional outcome after CNS injury. Research towards potential interventions for spinal cord and other CNS injuries must therefore be aimed at both of these targets. Hence, my laboratory focuses on two principal goals. Investigating the role of inflammatory mechanisms in degeneration and regeneration in the injured central nervous system (CNS), in particular the spinal cord, and the interactions of inflammatory mechanisms with these critical processes. The complement system is a principal effector for multiple inflammatory mechanisms, from phagocytosis to lytic cell loss, however, little attention has been paid to investigating the complement system after spinal cord injury. In recent studies, we have shown that all pathways of complement are activated after spinal cord injury, and defined the cellular localization and timecourse of immunoreactivity for complement in mice and rats. Additional studies of the effects of complement inhibitors on histological and functional outcome after contusion spinal cord injury suggest that this line of research may provide insight into potential therapeutics. Ongoing and planned studies include:

Investigating the cellular source of complement in the spinal cord.
Using transgenic mice lacking complement components to clarify the role and contribution of complement to CNS injury.
Investigating the interaction between enriched environment/physical exercise, immune function, and outcome after spinal cord/CNS injury.
These studies are important to understand the interactions of the immune and central nervous systems, and to determine whether complement inhibitors or therapeutics could be of benefit after human spinal cord injury.

Investigating the ability to use human stem cells to ameliorate the functional deficits associated with spinal cord injuries and promote recovery. Stem cells are a strong focus of current interest for the potential treatment of many types of CNS disease and injury. While the majority of stem cell lines that have currently been isolated are uncommitted and must be cultured in the presence of molecules that influence their cell fate prior to transplantation, the cells our laboratory works with are neural-committed. These human central nervous system stem cells (hCNS-SC) have been shown to migrate extensively after grafting into the uninjured fetal and adult brain, and to differentiate into functional neurons, as well as oligodendrocytes, and astrocytes. These projects make use of NOD-Scid mice, which immunodeficient and therefore exhibit a much attenuated rejection of xenografted (human to mouse) cells. Current studies show that NOD-Scid mice respond to spinal cord contusion injuries similar to background strain, and that transplantation of hCNS-SC into contusion-injured Nod-Scid mice leads to improvements in functional recovery. Ongoing and planned studies include:

Investigating and comparing NOD-Scid and NOD mice for spinal cord injury response characteristics.
Investigating the engraftment, survival, and differentation of hCNS-SC neurospheres in spinal cord injured NOD-Scid mice, the ability of these cells to promote recovery from injury, and the mechanisms by which this recovery takes place.

PubMed Link

http://www.ncbi.nlm.nih.gov/pubmed/?term=anderson+aj+AND+irvine[Affiliation]

Director - Aileen J. Anderson, Ph.D., Professor