Faculty Interests Database

Faculty Affairs: Faculty Interests Database Lorraine Iacovitti, PhD

Thomas Jefferson University
Jefferson Medical College
Associate Director & Laboratory Head, Farber Institute for Neurosciences

Department of Neurology
Appointed: 1998

Mailing Address Contact Information
900 Walnut Street
Philadelphia, Pennsylvania 19107
United States
Phone: (215) 955-8118
Fax: (215) 955-2992
Post-Doctoral, Washington University-St. Louis, 1979-81 (Anatomy & Neurobiology)

Ph.D., Cornell University Medical College, 1979 (Neurobiology)

B.S., Monmouth College, 1973 (Biology)
Expertise and Research Interests
Neurobiologist Lorraine Iacovitti heads the Parkinson's disease research group at the Farber Institute. She has pioneered methods for developing cell replacement therapies for Parkinson's disease using stem cells. She receives significant funding for her research from the National Institutes of Health (NIH), and has served on numerous study sections and review panels for the NIH and the National Science Foundation.

Research in Iacovitti's laboratory is 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. A major goal of our studies has been defining the molecular mechanisms (receptors, signal transduction pathways, etc.) that underlie initiation of the gene for the first and rate-limiting enzyme in dopamine biosynthesis, tyrosine hydroxylase. Our hope is that an understanding of the 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 stem or precursor cells, toward that phenotype. Using an approach that combines cell culture and genetic engineering, our aim is to induce dopaminergic traits in mouse and human stem/progenitor cells and devise ways to isolate those cells as pure dopamine neurons for study after transplantation in rat and monkey models of Parkinson's disease.

Current Research Programs:
· Human Tyrosine Hydroxylase Gene Promoter
· Generating A Population Of Pure Dopamine Neurons
· Stem Cell Grafts In Animal Models Of Parkinson's
Other Expertise
1995-1998 University Grievance Committee
1997-1998 University Steering Committee for the Faculty (elected)
1998-2000 Chairman, Research Committee, Department of Neurology
1998-2000 University Research Council
2000-2001 Co-chairman, University Research Committee
2001-2005 Chairman, University Research Committee

NSF Grant Reviewer - 1983-present
NIH Study Section Subcommittee NLS 1 - 1991, 1992, 1993, 1997
NIH NRSA Study Section- 1997
NIH Special Review Panel- Parkinson's Disease Center Grants- 1998
Philadelphia Chapter of the Society for Neuroscience 1996-1998
Drexel University Honors Program in Science, Consultant 1997-1999
Board of Trustees, Educational Committee, Germantown Academy 1997-1999
Advisor, The Lee Foundation 1998

1983-present NSF Grant Reviewer
1991, 1992, 1993, 1997 NIH Study Section Subcommittee NLS 1
1998,1999, 2000 NIH Special Review Panel- Parkinson's Disease Center of Excellence Grants

Journal of Neuroscience, Neuroscience, Journal of Neurochemistry, Developmental Biology, Neuroscience Letters, Journal of Neurobiology, Anatomy and Embryology, Journal of Neurocytology, Neuroendocrinology, Biotechniques
  • Representative Publications
  • Iacovitti L, Donaldson AE, Marshall CE, Suon S, and Yang M. A simple, rapid and chemically defined program for the differentiation of human embryonic stem cells into dopaminergic neurons in vitro and in vivo. Stem Cells 2005. In Press.
  • Jin H, Romano G, Marshall CE, Donaldson AE, Suon S, and Iacovitti L. Tyrosine hydroxylase gene regulation in human neuronal progenitor cells does not depend on Nurr1 as in the murine and rat systems. J. Cell Physiol 2005. In Press.
  • Donaldson AE, Marshall CE, Yang M, Suon S, and Iacovitti L. Purified mouse dopamine neurons thrive and function after transplantation into brain but require novel glial factors for survival. Mol. Cell. Neurosci 2005;30:108-117.
  • Romano G, Suon S, Donaldson AE, Jin H and Iacovitti L. Characterization of five evolutionary conserved regions of the human tyrosine hydroxylase (TH) promoter: implications for the engineering of a human TH minimal promoter. J. Cell Physiol 2005; 204:666-677.
  • Suon S, Jin H, Donaldson AE, Caterson EJ, Tuan RS, Deschennes G, Marshall C, and Iacovitti L. Adult human bone marrow stem cells transiently differentiate in culture to express CNS proteins. Stem Cells and Develop 2004;13:625-635.
  • Yang M, Donaldson AE, Marshall CE, Shen J, Iacovitti L. Studies on the differentiation of dopaminergic traits in human neural progenitor cells in vitro and in vivo. Cell Transplantation 2004. In Press.
  • Yang M, Donaldson AE, Jiang Y, Iacovitti L. Factors influencing the differentiation of dopaminergic traits in transplanted neural stem cells. Mol Cell Neurobiol 2003 Oct;23(4-5):851-64.
  • Kessler MA, Yang M, Gollomp KL, Jin H, Iacovitti L. The human tyrosine hydroxylase promoter. Brain Res Mol Brain Res 2003 Apr 10;112(1-2):8-23.
  • Yang M, Stull ND, Snyder EY, Berk MA, Iacovitti L. Neuronal stem cells spontaneously differentiate into dopaminergic neurons after transplantation into the intact or 6-hydroxydopamine lesioned rate. Exp Neurol 2002;177:50-60.
  • Stull ND, Polan DL, Iacovitti L. Antioxidant compounds protect dopamine neurons from death due to oxidative stress in vitro. Brain Res 2002;931: 181-185.
  • Stull ND, Jung JW, Iacovitti L. Induction of a dopaminergic phenotype in cultured striatal neurons by bone morphogenetic proteins. Brain Res Dev Brain Res. 2001 Sep 23;130(1):91-8.
  • Iacovitti L, Stull ND, Jin H. Differentiation of human dopamine neurons from an embryonic carcinomal stem cell line. Brain Res. 2001 Aug 31;912(1):99-104.
  • Zhou J, Iacovitti L. Mechanisms governing the differentiation of a serotonergic phenotype in culture. Brain Research. 877(1): 37-46, 2000
  • Iacovitti L, Stull ND, Mishizen A. Neurotransmitters, KCl and antioxidants rescue striatal neurons from apoptotic cell death in culture. Brain Research. 816(2): 276-85, Jan 1999
  • Guo Z, Du X, Iacovitti L. Regulation of tyrosine hydroxylase gene expression during transdifferentiation of striatal neurons: changes in transcription factors binding the AP-1 site. Journal of Neuroscience. 18(20): 8163-74, Oct 1998
  • Du X, Iacovitti L. Multiple signaling pathways direct the initiation of tyrosine hydroxylase gene expression in cultured brain neurons. Brain Research. Molecular Brain Research. 50(1-2): 1-8, Oct 1997
  • Iacovitti L, Stull ND, Johnston K. Melatonin rescues dopamine neurons from cell death in tissue culture models of oxidative stress. Brain Research. 768(1-2): 317-26, Sep 1997
  • Schinstine M, Iacovitti L. 5-Azacytidine and BDNF enhance the maturation of neurons derived from EGF-generated neural stem cells. Experimental Neurology. 144(2): 315-25, Apr 1997
  • Iacovitti L, Stull ND. Expression of tyrosine hydroxylase in newly differentiated neurons from a human cell line (hNT). Neuroreport. 8(6): 1471-4, Apr 1997
  • Du X, Iacovitti L. Protein kinase C activators work in synergy with specific growth factors to initiate tyrosine hydroxylase expression in striatal neurons in culture. Journal of Neurochemistry. 68(2): 564-9, Feb 1997
  • Stull ND, Iacovitti L. Acidic fibroblast growth factor and catecholamines synergistically up-regulate tyrosine hydroxylase activity in developing and damaged dopamine neurons in culture. Journal of Neurochemistry. 67(4): 1519-24, Oct 1996
  • Schinstine M, Iacovitti L. Expression of neuronal antigens by astrocytes derived from EGF-generated neuroprogenitor cells. Experimental Neurology. 141(1): 67-78, Sep 1996
  • Jin BK, Iacovitti L. Dopamine differentiation factors increase striatal dopaminergic function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mice. Journal of Neuroscience Research. 43(3): 331-4, Feb 1996
  • Max SR, Bossio A, Iacovitti L. Co-expression of tyrosine hydroxylase and glutamic acid decarboxylase in dopamine differentiation factor-treated striatal neurons in culture. Brain Research. Developmental Brain Research. 91(1): 140-2, Jan 1996
  • Du X, Iacovitti L. Synergy between growth factors and transmitters required for catecholamine differentiation in brain neurons. Journal of Neuroscience. 15(7 Pt 2): 5420-7, Jul 1995
  • Du X, Stull ND, Iacovitti L. Brain-derived neurotrophic factor works coordinately with partner molecules to initiate tyrosine hydroxylase expression in striatal neurons. Brain Research. 680(1-2): 229-33, May 1995
  • Jin BK, Iacovitti L. Dopamine differentiation factors produce partial motor recovery in 6-hydroxydopamine lesioned rats. Neurobiology of Disease. 2(1): 1-12, Feb 1995
  • Du X, Stull ND, Iacovitti L. Novel expression of the tyrosine hydroxylase gene requires both acidic fibroblast growth factor and an activator. Journal of Neuroscience. 14(12): 7688-94, Dec 1994
  • Kerr CW, Lee LJ, Romero AA, Stull ND, Iacovitti L. Purification of dopamine neurons by flow cytometry. Brain Research. 665(2): 300-6, Dec 1994
  • Stull ND, Schneider JS, Iacovitti L. GM1 ganglioside partially rescues cultured dopaminergic neurons from MPP( )-induced damage: dependence on initial damage and time of treatment. Brain Research. 640(1-2): 308-15, Mar 1994
  • Iacovitti L. Centrally active differentiation factors in the nervous system. Pharmacology and Therapeutics. 62(3): 373-83, 1994
  • Iacovitti L, Evinger MJ, Stull ND. Muscle-derived differentiation factor increases expression of the tyrosine hydroxylase gene and enzyme activity in cultured dopamine neurons from the rat midbrain. Brain Research. Molecular Brain Research. 16(3-4): 215-22, Dec 1992
  • Shirao T, Evinger MJ, Iacovitti L, Reis DJ. Lesions of nigrostriatal pathway reduce expression of tyrosine hydroxylase gene in residual dopaminergic neurons of substantia nigra. Neuroscience Letters. 141(2): 208-12, Jul 1992
  • Iacovitti L. Effects of a novel differentiation factor on the development of catecholamine traits in noncatecholamine neurons from various regions of the rat brain: studies in tissue culture. Journal of Neuroscience. 11(8): 2403-9, Aug 1991
  • Katz IR, Iacovitti LM, Reis DJ. In vitro studies on the characterization of cellular proliferation following neuronal injury in the adult rat brain. Journal of Neuroimmunology. 29(1-3): 33-48, 1990
  • Ernsberger P, Iacovitti L, Reis DJ. Astrocytes cultured from specific brain regions differ in their expression of adrenergic binding sites. Brain Research. 517(1-2): 202-8, May 1990
  • Iacovitti L, Evinger MJ, Joh TH, Reis DJ. A muscle-derived factor(s) induces expression of a catecholamine phenotype in neurons of cultured rat cerebral cortex. Journal of Neuroscience. 9(10): 3529-37, Oct 1989
  • Katz IR, Iacovitti L, Reis DJ. Cells proliferating in vitro to local brain injury are primarily of hematic origin and differ from those associated with anterograde degeneration. Annals of the New York Academy of Sciences. 540: 413-5, 1988
  • Iacovitti L, Teitelman G, Joh TH, Reis DJ. Chick eye extract promotes expression of a cholinergic enzyme in sympathetic ganglia in culture. Brain Research. 430(1): 59-65, May 1987
  • Iacovitti L, Lee J, Joh TH, Reis DJ. Expression of tyrosine hydroxylase in neurons of cultured cerebral cortex: evidence for phenotypic plasticity in neurons of the CNS. Journal of Neuroscience. 7(4): 1264-70, Apr 1987
  • Iacovitti L, Joh TH, Albert VR, Park DH, Reis DJ, Teitelman G. Partial expression of catecholaminergic traits in cholinergic chick ciliary ganglia: studies in vivo and in vitro. Developmental Biology. 110(2): 402-12, Aug 1985
  • Teitelman G, Joh TH, Grayson L, Park DH, Reis DJ, Iacovitti L. Cholinergic neurons of the chick ciliary ganglia express adrenergic traits in vivo and in vitro. Journal of Neuroscience. 5(1): 29-39, Jan 1985
  • Higgins D, Iacovitti L, Burton H. Fetal rat sympathetic neurons maintained in a serum-free medium retain induced cholinergic characteristics. Brain Research. 316(1): 71-82, May 1984
  • Iacovitti L, Johnson MI, Joh TH, Bunge RP. Biochemical and morphological characterization of sympathetic neurons grown in a chemically-defined medium. Neuroscience. 7(9): 2225-39, 1982
  • Iacovitti L, Joh TH, Park DH, Bunge RP. Dual expression of neurotransmitter synthesis in cultured autonomic neurons. Journal of Neuroscience. 1(7): 685-90, Jul 1981
  • Higgins D, Iacovitti L, Joh TH, Burton H. The immunocytochemical localization of tyrosine hydroxylase within rat sympathetic neurons that release acetylcholine in culture. Journal of Neuroscience. 1(2): 126-31, Feb 1981
  • Iacovitti L, Reis DJ, Joh TH. Reactive proliferation of brain stem noradrenergic nerves following neonatal cerebellectomy in rats: role of target maturation on neuronal response to injury during development. Brain Research. 227(1): 3-24, Jan 1981
  • Iacovitti L, Gershon MD. Induction of lipid droplet accumulation in cardiac muscle cells of guinea pigs and mice: an analysis of the effects of reserpine and fasting. Anatomical Record. 191(3): 327-43, Jul 1978
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