PI: Dou, Huanyu BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Huanyu Dou, MD Assistant professor eRA COMMONS USER NAME DOU.HUANYU EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and DEGREE include postdoctoral training.) INSTITUTION AND LOCATION YEAR(s) FIELD OF STUDY (if applicable) Weifang Medical College, China Bar-Ilan University, ISRAEL University of Nebraska Medical Center MD Postdoctoral Fellow Postdoctoral Fellow 1982 Medicine 2000-2001 Neurosciences 2002-2005 Neurovirology, nanomedicine A. Positions and Honors. 1982-1985 Physician, Rong Jun Hospital 1985-1990 Physician/Instuctor professor, Department of Medicine, Weifang Medical College,Shandon, China 1993-1995 Assistant Professor, Physician, Department of Anatomy, Weifang Medical College, China 1995-2000 Associte Professor,Vice-Director, Department of Anatomy, Center Morphology, Weifang Medical College, China 2000-2001 Postdoctoral Fellow, Laboratory of Zvi Malik, Unit of Microscopy, Faculty of Life Sciences of Bar-Ilan University, Israel 2002 – 2005 Fellow, CNND, Department of Pathology/Microbiology, University of Nebraska Medical Center, Omaha, NE, USA 2005 – 2007 Instructor and Director of Neurotherapeutics Program, Department of Pharmacology and Experimental Neuroscience and Center for Neurovirology and Neurodegenerative Disorders (CNND) 2008–present Assistant professor, Department of Pharmacology and Experimental Neuroscience and Center for Neurovirology and Neurodegenerative Disorders (CNND), Center for Drug Delivery and Nanomedicine (CDDN B. Research Support Active: 1 P20 RR021937-01A2 09/26/2008 - 06/30/2013 DHHS/NIH/NCRR $1,473,976 Role: PI of project 3 “Cell-based nanoformulations for brain tumors” Nebraska Center for Nanomedicine This proposal seeks to develop an interdisciplinary Nanomedicine Center at the University of Nebraska Medical Center. We have assembled a team of scientists with specific expertise in nanomedicine, drug delivery, therapeutics and diagnostics. These will now be joined by biochemists, pharmacologists, immunologists and neuroscientists. All will work, with singular focus, to develop the means to best use devices of nanoscale size to improve outcomes for cancer, neurodegenerative and cardiovascular diseases. Such approaches will deliver drugs to focal areas of central nervous system disease or directly to tumors. Parallel studies seek 1 PI: Dou, Huanyu nanotechnologies to improve diagnostic measures and disease monitoring. The anticipated outcome is to maximize clinical benefits and limit untoward side effects. 5 R01 NS36126-13 PI: Gendelman) 04/01/2008 - 03/31/2013 DHHS/NIH/NINDS $305,335 Role: Co-I Nanomedicine and NeuroAIDS This research proposes to investigate the biophysiological properties of monocytes and monocytederived macrophages that influence cell migration both across the blood-brain barrier and within the brain. The central hypothesis is that changes in ion channel expression in monocytes and macrophages following exposure to virus and immune products influences the cell's ability to change its volume and shape, thus influencing cell migration. Such events are pivotal for macrophages to enter the brain and to secrete the toxins that underlie the neuropathogenesis of HIV-1 associated dementia. C. Selected Publications: (from 41) Greenbaum L, Katcoff DJ, Dou H, Gozlan Y, Malik Z. A porphobilinogen deaminase (PBGD) Ran-binding protein interaction is implicated in nuclear trafficking of PBGD in differentiating glioma cells. Oncogene. 2003 Vol. 22(34): 5221-8. Dou H, Birusingh K, Faraci J, Gorantla S, Poluektova LY, Maggirwar SB, Dewhurst S, Gelbard HA, Gendelman HE. Neuroprotective activities of sodium valproate in a murine model of human immunodeficiency virus-1 encephalitis. J Neurosci. 2003 Vol. 23(27):9 162-70. Boska MD, Mosley RL, Nawab M, Nelson JA, Zelivyanskaya M, Poluektova L, Uberti M, Dou H, Lewis TB, Gendelman HE. Advances in neuroimaging for HIV-1 associated neurological dysfunction: clues to the diagnosis, pathogenesis and therapeutic monitoring. Current HIV research. 2004 (2): 61-78. Poluektova L, Gorantla S, Faraci J, Birusingh K, Dou H, Gendelman HE. Neuroregulatory events follow adaptive immune-mediated elimination of HIV-1-infected macrophages: studies in a murine model of viral encephalitis. J Immunol. 2004 Vol. 172(12): 7610-7. Dou H, Kingsley JD, Mosley RL, Gelbard HA, Gendelman HE. Neuroprotective strategies for HIV-1 associated dementia. Neurotox Res. 2004 Vol. 6(7-8): 503-21. Nelson JA*, Dou H*, Ellison B, Uberti M, Xiong H, Anderson E, Mellon M, Gelbard HA, Boska M, Gendelman HE. Coregistration of quantitative proton magnetic resonance spectroscopic imaging with neuropathological and neurophysiological analyses defines the extent of neuronal impairments in murine human immunodeficiency virus type-1 encephalitis. J Neurosci Res. 2005 Vol. 80(4): 562-75. Potula R, Poluektova L, Knipe B, Chrastil J, Heilman D, Dou H, Takikawa O, Munn DH, Gendelman HE, Persidsky Y. Inhibition of Indoleamine 2,3-dioxygenase (IDO) enhances elimination of virus-infected macrophages in animal model of HIV-1 encephalitis. Blood. 2005 Vol. 106(7): 2382-90. Kingsley JD, Dou H, Morehead J, Rabinow BE, Gendelman HE, Destache CJ. 2 PI: Dou, Huanyu Nanotechnology: A Focus on Nanoparticles as a Drug Delivery System. Journal of Neuroimmune Pharmacology. 2006 (1): 340-350. Dou H, Ellison H, Bradley J, Kasiyanov A, Poluektova L, Xiong H, Maggirwar S, Dewhurst S, Gelbard HA, and Gendelman HE. Neuroprotective mechanisms of lithium in murine HIV-1 encephalitis. J Neurosci, 2005 Vol. 25(37): 8375-85. Potula R, Haorah J, Knipe B, Leibhart J, Chrastil J, Heilman D, Dou H, Reddy R, Ghorpade A, Persidsky Y. Alcohol abuse enhances neuroinflammation and impairs immune responses in an animal model of human immunodeficiency virus-1 encephalitis. Am J Pathol. 2006 Vol. 168(4): 1335-44. Dou H, Morehead J, Bradley J, Gorantla S, Ellison B, Kingsley J, Smith LM, Chao W, Bentsman G, Volsky DJ, Gendelman HE. Neuropathologic and neuroinflammatory activities of HIV-1-infected human astrocytes in murine brain. Glia. 2006 Vol. 54(2): 81-93. Dou H, Destache CJ, Morehead JR, Mosley RL, Boska MD, Kingsley J, Gorantla S, Poluektova L, Nelson JA, Chaubal M, Werling J, Kipp J, Rabinow BE, Gendelman HE. Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery. Blood. 2006 Vol. 108(8): 2827-35. Gorantla S, Dou H, Boska M, Destache CJ, Nelson J, Poluektova L, Rabinow BE, Gendelman HE, Mosley RL. Quantitative magnetic resonance and SPECT imaging for macrophage tissue migration and nanoformulated drug delivery. J Leukoc Biol. 2006 Vol. 80(5): 1165-74. Peng H, Erdmann N, Whitney N, Dou H, Gorantla S, Gendelman HE, Ghorpade A, Zheng J. HIV-1-infected and/or immune activated macrophages regulate astrocyte SDF-1 production through IL-1beta. Glia. 2006 Vol. 54(6): 619-29. Dou H, Morehead J, Destache CJ, Kingsley JD, Shlyakhtenko L, Zhou Y, Chaubal M, Werling J, Kipp J, Rabinow BE, Gendelman HE. Laboratory investigations for the morphologic, pharmacokinetic, and anti-retroviral properties of indinavir nanoparticles in human monocytederived macrophages. Virology. 2007 Vol.358(1): 148-58. Gorantla S, Liu J, Sneller H, Dou H, Holguin A, Smith L, Ikezu T, Volsky DJ, Poluektova L, Gendelman HE. Copolymer-1 Induces Adaptive Immune Anti-inflammatory Glial and Neuroprotective Responses in a Murine Model of HIV-1 Encephalitis. J Immunol. 2007 Vol. 179(7): 4345-56. Peng H, Whitney N, Wu Y, Tian C, Dou H, Zhou Y, Zheng J. HIV-1-infected and/or immuneactivated macrophage-secreted TNF-alpha affects human fetal cortical neural progenitor cell proliferation and differentiation.Glia. 2008 Jun;56(8):903-16. Liu Y, Uberti MG, Dou H, Banerjee R, Grotepas CB, Stone DK, Rabinow BE, Gendelman HE, Boska MD. Ingress of blood-borne macrophages across the blood-brain barrier in murine HIV1 encephalitis. J Neuroimmunol. 2008 Aug 30;200(1-2):41-52. Potula R, Ramirez SH, Knipe B, Leibhart J, Schall K, Heilman D, Morsey B, Mercer A, Papugani A, Dou H, Persidsky Y. Peroxisome proliferator-activated receptor-gamma activation 3 PI: Dou, Huanyu suppresses HIV-1 replication in an animal model of encephalitis. AIDS. 2008 Aug 20;22(13):1539-49 Beduneau A, Ma Z, Grotepas CB, Kabanov A, Rabinow BE, Gong N, Mosley RL, Dou H, Boska MD, Gendelman HE. Facilitated monocyte-macrophage uptake and tissue distribution of superparmagnetic iron-oxide nanoparticles. PLoS One. 2009;4(2):e4343. Dou H, Grotepas CB, Zeng C, Boska MD, Destache CJ, Chaubal M, Werling J, Kipp J, Rabinow BE, Gendelman HE. Macrophage delivery of nanoformulated anti retroviral drug to the brain in a murine model of neuroAIDS. J. of Immunology, 2009 Jul 1;183(1):661-9. Nowacek AS, Miller RL, McMillan J, Kanmogne G, Kanmogne G, Mosley RL, Ma Z, Graham S, Chaubal M, WerlingJ, Rabinow R, Dou H, and Gendelman HE. NanoART Synthesis, Characterization, Uptake, Release, and Toxicology for Human Monocyte-Macrophage Drug Delivery. J. of Immunology, in submission. Invited Talks: 1. December 5, 2008. Research seminar Department of anatomy, Philadelphia College of Osteopathic Medicine, Philadelphia, PA 2. January 9, research seminar, Department of Neurology & Pittsburgh Institute of Neurodegenerative Disease, University of Pittsburg, Pittsburg, PA 3. April 27, 2009, research seminar, Department of Public Health Sciences, University of Hawaii at Manoa 4. April 30, 2009, COBRE/APITMID Seminar Series, John A. Burns School of Medicine, University of Hawaii at Manoa 5. Invited speaker, First World Congress of International Academy of Nanomedicine (IANM). Jun 12-13, 2009, Sanya, Hainan, China 6. Invited speaker, NIDA cutting Edge Seminar, Tuesday, September 1, 2009, Bethesda, MD 20892 4