The Dennis Steindler Lab

Research Publications Neuroscience

 

Stem Cells, Regenerative and Integrated Medicine Therapies in Neurologic Disorders

Our laboratory focuses on the combined use of stem cell, regenerative and integrated medicine therapies for debilitating neurological diseases and injuries. There is widespread interest in the use of stem cells for cell replacement therapies in human neurological disease and stroke; however, we have only begun to appreciate the cell and molecular biology of these cells that hold great promise for transplantation or other therapeutics relying on the use of different stem/progenitor cell populations or biogenic factors associated with their growth for many repair or cancer treatment approaches.

Steindler Fig 1

Fig 1. A cell culture plated and differentiating neurosphere clone derived from a single mouse neural stem cell. Green cells are astrocytes immunolabeled for glial fibrillary acidic protein, red cells are young neurons labeled for beta III tubulin, and blue nuclear counterstaining.

In addition to augmenting the ex vivo expansion, and attempting to control fate and differentiation of stem/progenitor cells isolated from various sources including the postnatal and adult periventricular subependymal zone using culture methods developed in our lab that affect cell-cell and cell-substrate (e.g. extracellular matrix) interactions, we also are using new molecular approaches (e.g. profiling single stem/progenitor cells) to characterize novel developmental genes and glycoconjugates involved in cell genesis, survival, differentiation and cell death. The main strategy of these studies is to exploit well-known approaches for gaining access to transmembrane signaling pathways that direct cell survival, proliferation, and fate determination. As these profiling studies are refined, future approaches can rely on stem/progenitor cells as vehicles or targets for gene and molecular therapies in human disease. It is hopeful that gene-discovery, and studying biogenic factors for and from stem cells, will lead to the development of new drugs that expand or deter typically quiescent stem cell populations, and lead to their control during neoplasia or migration and differentiation within cell-deficient targets without the need for ex vivo manipulation and grafting. Our lab also studies cellular morphotypes, genes and molecules involved in stem/progenitor cell growth associated with pediatric and adult tumors in brain, bone and colon. Since our lab was the first to demonstrate a solid tumor stem-like cell, the brain glioma neurosphere-generating cell, we are interested in comparing normal and abnormal tissue generation and gene expression associated with potent cells from a variety of normal and cancerous tissues.

The studies listed above all 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 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 tissues and organs that represent particular hallmarks of degenerative and oncogenic disease to create so-called patient/disease-specific avatar mice. This is in keeping with the convergence of transplantation and oncogenic transformation studies in the bone marrow hematopoiesis research field. The study of adult human brain neuropoiesis for example likewise requires rigorous experimental investigation of the biology of neural stem cells, as has been applied to their counterparts in blood.

Most recent stem cell studies in the lab are looking at: 1. Near-future applications of neuroprotection and neurorepair that rely on in vitro and in vivo exosome biomarker studies in neurodegenerative disorders and brain cancer, as well as applying insights gained from comparative vertebrate regenerative biology to human regenerative medicine; and, 2. Application of biogenic compounds as therapeutics for a variety of neurological diseases and cancers, including use of botanical and other nutrient and molecular therapeutics to be used along side of standard of care approaches to improve survival and quality of life for pediatric and adult solid tumor cancers, and neurodegenerative diseases including Parkinson’s and Alzheimer’s, as well as age-related cognitive decline where chronic inflammation that can be associated with pathological aging represents a major underlying contributor to disease.

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The priority application deadlines are as follows:

December 1: Basic Science Division PhD Programs

February 15: Building Diversity in Biomedical Sciences

March 31: Post-Baccalaureate Research Program

May 1: Clinical & Translational Science, MS in Pharmacology & Drug Development

June 15: Online Certificate in Fundamentals of Clinical Care Research