Marina Emborg, M.D., Ph.D.

Associate Professor

Department Affiliations

Medical Physics

Wisconsin National Primate Research Center

Neuroscience Training Program

Stem cell and regenerative Medicine

Biomedical Engineering Program

Cellular and Molecular Pathology Program

Education

M.D., Universidad de Buenos Aires, Buenos Aires.

Ph.D., Neurobiology. Universidad de Buenos Aires, Buenos Aires. Thesis Title: Parkinson's disease: analysis of the intracarotid MPTP model. Plasticity of the system [Enfermedad de Parkinson: estudio de un modelo experimental por administracion intracarotdea de MPTP en primates. Plasticidad del sistema].

Research Interests

The goal of my lab is to understand and find solutions for neurodegenerative disorders, in particular Parkinson's disease (PD). We work in a highly collaborative and interdisciplinary environment. We search for safe neuroprotective strategies that will prevent, slow down or stop death of brain cells, and use stem cells as model systems and as cell-based strategies.

Application and development of advanced imaging techniques are essential to our preclinical research. Neuroimaging methods let us estimate in a non invasive manner neuronal cell degeneration, adaptive responses to injury and the effect of therapeutic interventions. We use different radioligands, such as ₁₈F Fluoro-L-3,4- dihydroxyphenylalanine (F-DOPA), to assess the integrity of the dopaminergic system. As an alternative to the use of radio-labeled markers of the dopaminergic pathway (that maybe influenced by dopamine replacement therapies), we study the pattern of resting glucose metabolism as measured by [₁₈F]2-fluoro-2- deoxy-D-gluocose (FDG), to evaluate the metabolic responses to lesions and treatments in the brain. Non nigrostriatal-related symptoms of PD, like heart dysautonomia, are examined by [₁₁C] carbon-11-meta-ephedrine uptake. We apply in vivo MRI techniques for accurate real-time intracerebral targeting and infusion monitoring with the goal of minimizing the impact of invasive procedures, maximize data collection, and facilitate new clinical applications, including convection enhanced delivery for gene therapy.

Positions

• Associate Professor, Department of Medical Physics, University of Wisconsin-School of Medicine and Public Health, Madison, WI

• Scientist, Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI

Awards and Honors

• Young Scholar Travel Grant Award, Fundacion Argentina de Neurocirugia, 1990

• Research Fellow Award, CONICET (Comisión Nacional de Investigaciones Científicas y Técnicas), 1993.

Memberships

• Society for Neuroscience

• American Association for the Advancement of Science

• American Society of Gene Therapy

• American Society for Neutral Therapy

• The Gerontological Society of America

Publications

• Intraoperative Intracerebral MRI-Guided Navigation for Accurate Targeting in Nonhuman Primates. Emborg ME, Joers V, Fisher R, Brunner K, Carter V, Ross C, Raghavan R, Brady M, Raschke J, Kubota K, Alexander A. Cell Transplant. 2010;19(12):1587-97. Epub 2010 Jun 29. PMID: 20587170

• Research ethics. Beyond access vs. protection in trials of innovative therapies. London AJ, Kimmelman J, Emborg ME. Science. 2010 May 14;328(5980):829-30. PMID: 20466907

• Evaluation of hydrodynamic limb vein injections in nonhuman primates. Hegge JO, Wooddell CI, Zhang G, Hagstrom JE, Braun S, Huss T, Sebestyén MG, Emborg ME, Wolff JA. Hum Gene Ther. 2010 Jul;21(7):829-42. PMID: 20163248

• Preclinical assessment of stem cell therapies for neurological diseases. Joers VL, Emborg ME. ILAR J. 2009;51(1):24-41. PMID: 20075496

• Launching invasive, first-in-human trials against Parkinson's disease: ethical considerations. Kimmelman J, London AJ, Ravina B, Ramsay T, Bernstein M, Fine A, Stahnisch FW, Emborg ME. Mov Disord. 2009 Oct 15;24(13):1893-901. PMID: 19672990

• Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF. Emborg ME, Moirano J, Raschke J, Bondarenko V, Zufferey R, Peng S, Ebert AD, Joers V, Roitberg B, Holden JE, Koprich J, Lipton J, Kordower JH, Aebischer P. Neurobiol Dis. 2009 Nov;36(2):303-11. Epub 2009 Aug 4. PMID: 19660547

• Cell-based therapies for Parkinson's disease: past, present, and future. Fitzpatrick KM, Raschke J, Emborg ME. Antioxid Redox Signal. 2009 Sep;11(9):2189-208. PMID: 19485712

• Can we prevent parkinson's disease? Swanson CR, Sesso SL, Emborg ME. Front Biosci. 2009 Jan 1;14:1642-60. PMID: 19273153

• Mood, memory and movement: an age-related neurodegenerative complex? Granholm AC, Boger H, Emborg ME. Curr Aging Sci. 2008 Jul;1(2):133-9. PMID: 20021382

• GDNF-secreting human neural progenitor cells increase tyrosine hydroxylase and VMAT2 expression in MPTP-treated cynomolgus monkeys. Emborg ME, Ebert AD, Moirano J, Peng S, Suzuki M, Capowski E, Joers V, Roitberg BZ, Aebischer P, Svendsen CN. Cell Transplant. 2008;17(4):383-95. PMID: 18522241

• Contributions of non-human primates to neuroscience research. Capitanio JP, Emborg ME. Lancet. 2008 Mar 29;371(9618):1126-35. PMID: 18374844

• Nonhuman primate models of Parkinson's disease. Emborg ME. ILAR J. 2007;48(4):339-55. PMID: 17712221

• Differential loss of presynaptic dopaminergic markers in Parkinsonian monkeys. Stephenson DT, Childs MA, Li Q, Carvajal-Gonzalez S, Opsahl A, Tengowski M, Meglasson MD, Merchant K, Emborg ME. Cell Transplant. 2007;16(3):229-44. PMID: 17503735

• Survival and early differentiation of human neural stem cells transplanted in a nonhuman primate model of stroke. Roitberg BZ, Mangubat E, Chen EY, Sugaya K, Thulborn KR, Kordower JH, Pawar A, Konecny T, Emborg ME. J Neurosurg. 2006 Jul;105(1):96-102. PMID: 16871883

• Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism. Emborg ME, Carbon M, Holden JE, During MJ, Ma Y, Tang C, Moirano J, Fitzsimons H, Roitberg BZ, Tuccar E, Roberts A, Kaplitt MG, Eidelberg D. J Cereb Blood Flow Metab. 2007 Mar;27(3):501-9. Epub 2006 Jul 12. PMID: 16835631

• Basal ganglia lesions after MPTP administration in rhesus monkeys. Emborg ME, Moirano J, Schafernak KT, Moirano M, Evans M, Konecny T, Roitberg B, Ambarish P, Mangubat E, Ma Y, Eidelberg D, Holden J, Kordower JH, Leestma JE. Neurobiol Dis. 2006 Aug;23(2):281-9. PMID: 16766201

• The effects of a selective dopamine D2 receptor agonist on behavioral and pathological outcome in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated squirrel monkeys. Stephenson DT, Meglasson MD, Connell MA, Childs MA, Hajos-Korcsok E, Emborg ME. J Pharmacol Exp Ther. 2005 Sep;314(3):1257-66. Epub 2005 Jun 24. PMID: 15980058

• Expression of GAD65 and GAD67 immunoreactivity in MPTP-treated monkeys with or without L-DOPA administration. Stephenson DT, Li Q, Simmons C, Connell MA, Meglasson MD, Merchant K, Emborg ME. Neurobiol Dis. 2005 Nov;20(2):347-59. PMID: 15882945

• Evaluation of animal models of Parkinson's disease for neuroprotective strategies. Emborg ME. J Neurosci Methods. 2004 Oct 30;139(2):121-43. PMID: 15488225

• Cell transplantation for Parkinson's disease. Roitberg B, Urbaniak K, Emborg M. Neurol Res. 2004 Jun;26(4):355-62. PMID: 15198860

• Blood vessels and parkinsonism. Barcia C, Emborg ME, Hirsch EC, Herrero MT. Front Biosci. 2004 Jan 1;9:277-82. PMID: 14766365

• Overlesioned hemiparkinsonian non human primate model: correlation between clinical, neurochemical and histochemical changes. Oiwa Y, Eberling JL, Nagy D, Pivirotto P, Emborg ME, Bankiewicz KS. Front Biosci. 2003 Sep 1;8:a155-66. PMID: 12957824

• Distribution of high affinity choline transporter immunoreactivity in the primate central nervous system. Kus L, Borys E, Ping Chu Y, Ferguson SM, Blakely RD, Emborg ME, Kordower JH, Levey AI, Mufson EJ. J Comp Neurol. 2003 Aug 25;463(3):341-57. PMID: 12820166

• Rest tremor in rhesus monkeys with MPTP-induced parkinsonism. Emborg ME, Tetrud JW, Moirano J, McLaughlin WW, Bankiewicz KS. Front Biosci. 2003 May 1;8:a148-54. PMID: 12700090

• Chronic ischemic stroke model in cynomolgus monkeys: behavioral, neuroimaging and anatomical study. Roitberg B, Khan N, Tuccar E, Kompoliti K, Chu Y, Alperin N, Kordower JH, Emborg ME. Neurol Res. 2003 Jan;25(1):68-78. PMID: 12564129

• The immunophilin ligand GPI-1046 does not have neuroregenerative effects in MPTP-treated monkeys. Eberling JL, Pivirotto P, Bringas J, Steiner JP, Kordower JH, Chu Y, Emborg ME, Bankiewicz KS. Exp Neurol. 2002 Dec;178(2):236-42. PMID: 12504882

• Lentivirally delivered glial cell line-derived neurotrophic factor increases the number of striatal dopaminergic neurons in primate models of nigrostriatal degeneration. Palfi S, Leventhal L, Chu Y, Ma SY, Emborg M, Bakay R, Déglon N, Hantraye P, Aebischer P, Kordower JH. J Neurosci. 2002 Jun 15;22(12):4942-54. PMID: 12077191

• Behavioral and morphological comparison of two nonhuman primate models of Huntington's disease. Roitberg BZ, Emborg ME, Sramek JG, Palfi S, Kordower JH. Neurosurgery. 2002 Jan;50(1):137-45; discussion 145-6. PMID: 11844244

• Systemic administration of the immunophilin ligand GPI 1046 in MPTP-treated monkeys. Emborg ME, Shin P, Roitberg B, Sramek JG, Chu Y, Stebbins GT, Hamilton JS, Suzdak PD, Steiner JP, Kordower JH. Exp Neurol. 2001 Mar;168(1):171-82. PMID: 11170732

• Technique for bilateral intracranial implantation of cells in monkeys using an automated delivery system. Bankiewicz KS, Bringas J, Pivirotto P, Kutzscher E, Nagy D, Emborg ME. Cell Transplant. 2000 Sep-Oct;9(5):595-607. PMID: 11144957

• Delivery of therapeutic molecules into the CNS. Emborg ME, Kordower JH. Prog Brain Res. 2000;128:323-32. PMID: 11105691

• Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. Kordower JH, Emborg ME, Bloch J, Ma SY, Chu Y, Leventhal L, McBride J, Chen EY, Palfi S, Roitberg BZ, Brown WD, Holden JE, Pyzalski R, Taylor MD, Carvey P, Ling Z, Trono D, Hantraye P, Déglon N, Aebischer P. Science. 2000 Oct 27;290(5492):767-73. PMID: 11052933

• Delayed onset of progressive dystonia following subacute 3-nitropropionic acid treatment in Cebus apella monkeys. Palfi S, Leventhal L, Goetz CG, Hantraye T, Roitberg BZ, Sramek J, Emborg M, Kordower JH. Mov Disord. 2000 May;15(3):524-30. PMID: 10830419

• Lentiviral gene transfer to the nonhuman primate brain. Kordower JH, Bloch J, Ma SY, Chu Y, Palfi S, Roitberg BZ, Emborg M, Hantraye P, Déglon N, Aebischer P. Exp Neurol. 1999 Nov;160(1):1-16. PMID: 10630186

• Age-related declines in nigral neuronal function correlate with motor impairments in rhesus monkeys. Emborg ME, Ma SY, Mufson EJ, Levey AI, Taylor MD, Brown WD, Holden JE, Kordower JH. J Comp Neurol. 1998 Nov 16;401(2):253-65.PMID: 9822152

• MPTP-Induced hemiparkinsonism in nonhuman primates 6-8 years after a single unilateral intracarotid dose. Emborg-Knott ME, Domino EF. Exp Neurol. 1998 Aug;152(2):214-20. PMID: 9710520

• Application of gene therapy for Parkinson's disease: nonhuman primate experience. Bankiewicz KS, Bringas JR, McLaughlin W, Pivirotto P, Hundal R, Yang B, Emborg ME, Nagy D. Adv Pharmacol. 1998;42:801-6. PMID: 9328019

• 6-[18F]fluoro-L-m-tyrosine: metabolism, positron emission tomography kinetics, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine lesions in primates. Jordan S, Eberling JL, Bankiewicz KS, Rosenberg D, Coxson PG, VanBrocklin HF, O'Neil JP, Emborg ME, Jagust WJ. Brain Res. 1997 Mar 7;750(1-2):264-76. PMID: 9098552

• Long-term MPTP-treated monkeys are resistant to GM1 systemic therapy. Emborg ME, Colombo JA. Mol Chem Neuropathol. 1994 Jan;21(1):75-82. PMID: 8179773