Dr. Iacovitti Lorraine Iacovitti, Ph.D.

Contact Dr. Iacovitti

900 Walnut St.
Suite 462
Philadelphia, PA 19107

215-955-8118
215-955-2992 fax

Graduate School
Cornell University Medical College, NY; PhD in Neurobiology

University Appointment
1998-present    Professor with tenure, Department of Neurology, Thomas Jefferson University
1995-1998    Professor in Neurobiology and Anatomy, Allegheny University of the Health Sciences, Philadelphia, PA
1989-1995    Associate Professor in Neurology, Hahnemann University, Philadelphia, PA. (aka (Allegheny University)
1988-1989    Associate Professor in Neurology, Cornell University Medical College, New York, NY
1981-1988    Assistant Professor in Neurology Cornell University Medical College, New York, NY

Research and Clinical Interests
Research in my laboratory has been aimed at understanding how neurons differentiate into dopamine neurons during development of the brain and how that information may be useful for the treatment of neurodegenerative diseases such as Parkinson's disease (PD). A major goal of our studies has been defining the key fate determinant genes and lineage stages in the development of human dopamine neurons. Our hope is that an understanding of those mechanisms that first direct expression of neurotransmitter genes during differentiation will provide a molecular blueprint that can be used to intentionally target the differentiation of cells such as human embryonic stem or adult induced pluripotent cells toward that phenotype. Using an approach that combines cell culture and animal models of PD, our aim is to induce dopaminergic traits in human stem cells and devise ways to amplify and purify prospective human dopamine neurons for the development of cell-based therapies in PD, for future studies of PD in the dish and for the production of a high throughput screen for PD drug discovery.

Also, in the last few years, we have begun to explore a neuroprotective strategy to treat PD disease. Using gene microarray analysis, candidate genes isolated from PD-spared ventral tegmental neurons of the midbrain have been analyzed for their neuroptotective properties on PD-susceptible substantia nigra neurons. These studies have revealed a number of interesting molecules, including the glycoprotein Gremlin-1, which has the capacity to rescue dopamine neurons from neurotoxic damage in vitro and in vivo.

In addition, recently we have expanded our studies on stem cells in the lab to explore their potential use as a treatment for stroke, which remains the leading cause of disability and the third leading cause of death in the US. Our work and that of others shows that IV injection of bone marrow stem cells significantly protects brain structure and reverses sensory and motor deficits after experimental stroke. In an effort to understand the mechanism of action through which stem cells mediate their striking effects, we are currently studying the molecular correlates that accompany stem cell-induced recovery in rat and tissue culture models of stroke.

Publications

Most recent Peer-reviewed Publications

  1. Evolutionary conservation of an atypical glucocorticoid-responsive element in the human tyrosine hydroxylase gene
  2. BMP and TGF-Β pathway mediators are critical upstream regulators of Wnt signaling during midbrain dopamine differentiation in human pluripotent stem cells
  3. Tracking Transplanted Bone Marrow Stem Cells and Their Effects in the Rat MCAO Stroke Model
  4. Gremlin is a novel VTA derived neuroprotective factor for dopamine neurons
  5. Changes in host blood factors and brain glia accompanying the functional recovery after systemic administration of bone marrow stem cells in ischemic stroke rats
  6. Cell-autonomous alteration of dopaminergic transmission by wild type and mutant (ΔE) TorsinA in transgenic mice
  7. VTA neurons show a potentially protective transcriptional response to MPTP
  8. Dopaminergic neurons derived from human induced pluripotent stem cells survive and integrate into 6-OHDA-lesioned rats
  9. Heterotopically transplanted CVO neural stem cells generate neurons and migrate with SVZ cells in the adult mouse brain
  10. Genetic ablation of caveolin-1 increases neural stem cell proliferation in the subventricular zone (SVZ) of the adult mouse brain
  11. Functional heterogeneity at dopamine release sites
  12. Human amniotic fluid stem cells do not differentiate into dopamine neurons in vitro or after transplantation in vivo
  13. Circumventricular organs: A novel site of neural stem cells in the adult brain
  14. The role of Lmx1a in the differentiation of human embryonic stem cells into midbrain dopamine neurons in culture and after transplantation into a Parkinson's disease model
  15. Expression of the LRRK2 gene in the midbrain dopaminergic neurons of the substantia nigra
  16. Transcription and epigenetic profile of the promoter, first exon and first intron of the human tyrosine hydroxylase gene
  17. A protocol for the differentiation of human embryonic stem cells into dopaminergic neurons using only chemically defined human additives: Studies in vitro and in vivo
  18. Adult human bone marrow stromal spheres express neuronal traits in vitro and in a rat model of Parkinson's disease
  19. Tyrosine hydroxylase gene regulation in human neuronal progenitor cells does not depend on Nurr1 as in the murine and rat systems
  20. Purified mouse dopamine neurons thrive and function after transplantation into brain but require novel glial factors for survival in culture.

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