Dennis A. Steindler, Ph.D.
Professor of Medical Research
Department of Neurosurgery
100 S Newell Drive, Room L3-100
Gainesville, FL 32610
Dr. Dennis A. Steindler received his Bachelors degree from the University of Wisconsin, Madison, in Zoology, his Ph.D. in Anatomy/Neuroscience from the University of California, San Francisco, and he did postdoctoral training at the Max Planck Institute for Biophysical Chemistry in Germany. He then joined the University of Florida College of Medicine faculty as a professor of neuroscience and neurosurgery.
Dr. Steindler became the Executive Director of the McKnight Brain Institute on December 1, 2004 and stepped down to focus more in the lab in late 2010.
The major research goal of Dr. Steindler’s program is to see the use of stem cell therapy become a major treatment for debilitating neurological diseases. There is widespread interest in the use of stem cells for cell replacement therapies in human neurological disease; however, we have only begun to appreciate the cell and molecular biology of these cells which hold great promise for transplantation or other therapeutics relying on the potential use of our own persistent stem/progenitor cell population in autologous repair paradigms. Five different but concurrently run sets of experiments aim to advance our understanding and use of neural stem cell therapies. The five approaches are:
- The development and refinement of new in vitro methodologies that, in part, rely on insights from studies of hematopoiesis to selectively expand particular stem or progenitor cell populations and also control their differentiation into particular types of neurons
- The discovery of genes involved in stem cell growth and differentiation using clonal populations of stem/progenitor cells as a model for neurogenesis, by way of creating cDNA libraries from normal and neurological disease brain
- Use of animal models of neurodegenerative disease by a dedicated transplant group in the lab that is refining methods of integrating grafted stem/progenitor cells into altered adult brain circuitries
- Stem cell plasticity and homing in a variety of tissues
- Studying distinct stem/progenitor cell populations as a potential source of primary tumors.
In addition to augmenting the ex vivo expansion, and attempting to control fate and differentiation of stem/progenitor cells isolated from the postnatal and adult periventricular subependymal zone using culture methods developed in our lab that affect cell-cell and cell-substrate interactions, we also are using new molecular approaches (e.g. cDNA libraries from single stem/progenitor cell clones) to characterize novel developmental genes involved in cell genesis, survival and cell death. The main strategy of these studies is to exploit well-known approaches for gaining access to signaling pathways that direct cell survival, proliferation, and fate determination. As these gene expression profiles are refined, future approaches can rely on stem/progenitor cells as vehicles for gene therapy in human disease.
It is even possible that gene-discovery studies will lead to the development of new drugs that expand our resident, quiescent stem/progenitor cell populations within marrow and other CNS sites, and lead to their migration and differentiation within cell-deficient targets without the need for ex vivo manipulation and grafting.
Finally, a part of our team has begun to exploit similar cell and molecular approaches to study cellular morphotypes and genes involved in stem/progenitor cell growth associated with pediatric and adult brain tumors. Again, gene discovery and subtractive methods are used to compare normal and abnormal gene expression associated with normal neurogenesis versus that seen in neurodegenerative disease and brain neoplasia.
The studies listed above compare cell and molecular characteristics of normal and transformed cells to define basic principles of normal and abnormal stem cell growth and differentiation. We rely on the use of transgenic mouse models of disease to isolate and characterize engineered or primed stem/progenitor cell populations, and then reintroduce and study these cells in altered tissues and compromised CNS circuitry arrangements that represent particular hallmarks of degenerative and oncogenic disease. This is in keeping with the convergence of transplantation and tumorigenesis studies in the bone marrow hematopoiesis field. The study of adult human brain neuropoiesis likewise requires rigorous experimental investigation of the biology of neural stem cells, as has been applied to their counterparts in blood.