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Doina Ganea, PhD

Earle H. Spaulding Chair in Microbiology and Immunology

Professor, Microbiology and Immunology

Office:  Medicine Education and Research Bldg. 1160

Telephone:  215-707-3207

Fax:  215-707-7788

Email: doina.ganea@temple.edu

Department of Microbiology and Immunology

Center for Substance Abuse Research

Temple Autoimmunity Center

BS, Physics, 1967

University of Bucharest, Romania

 

MS, Biophysics, 1969

Department of Biophysics

University of Bucharest, Romania

 

PhD, Immunology, 1985

Department of Microbiology and Immunology

University of Illinois at Chicago

Chicago, IL

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The major research interests and most of the current research in my laboratory are in the field of neuroimmunology and lipid immunology. Although the bidirectional communications between the neuroendocrine and the immune systems are well recognized today, the molecular mechanisms through which the two systems communicate are still being investigated. The understanding of the signaling between neuroendocrine, lipid and immune mediators is particularly relevant in diseases with strong inflammatory/autoimmune underlying mechanisms. The major research projects presently developed in our laboratory are focused on the effects of neuropeptides, cannabinoid receptor agonists, and lipid mediators on the immune system and response, particularly in inflammatory/autoimmune conditions. We investigate the mechanisms by which the neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) affect cytokine production in macrophages and T cells, including transduction pathways and transcriptional factors. We also study the effects of neuropeptides on T cell survival and differentiation into Th1/Th2 effector cells, and on the development of tolerogenic dendritic cells and subsequently of antigen-specific regulatory T cells. Recently, we developed a biological system for VIP delivery directly to the inflammatory site by using lentiviral vector transduced, VIP-secreting dendritic cells. Inoculation of VIP-secreting dendritic cells in models of multiple sclerosis and peritoneal sepsis proved highly beneficial. A new research project developed in collaboration with Dr. Ronald Tuma (CSAR) is focused on the effects of cannabinoid CB2 receptor agonists on immune cell trafficking in the CNS, and their effects on experimental models of multiple sclerosis, stroke, and spinal cord injury. Another major area of research is focused on the immunomodulatory effects of lipid mediators, especially n=6 and n=3 fatty acids. Our latest research demonstrated that n=6 derivatives such as prostaglandin E2 alters the expression of IL-12 family cytokines in dendritic cells, promoting the differentiation of the strong pro-inflammatory Th17 cells. In contrast, n=3 fatty acids such as DHA and omega 3 fatty acid derivatives such as Resolvin E1 and D1, are strong anti-inflammatory agents whose activity is mediated through effects on dendritic cells and T cell differentiation.

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

23532861. Habib MR, Ganea DA, Katz IK, Lamprecht R, ABL1 in thalamus is associated with safety but not fear learning. Front Syst Neurosci 7:(5)2013

23261777. Yen JH, Xu S, Park YS, Ganea D, Kim KC, Higher susceptibility to experimental autoimmune encephalomyelitis in Muc1-deficient mice is associated with increased Th1/Th17 responses. Brain Behav Immun 29:(70-81)2013 Mar

23027540. Nishimori JH, Newman TN, Oppong GO, Rapsinski GJ, Yen JH, Biesecker SG, Wilson RP, Butler BP, Winter MG, Tsolis RM, Ganea D, Tükel Ç, Microbial amyloids induce interleukin 17A (IL-17A) and IL-22 responses via Toll-like receptor 2 activation in the intestinal mucosa. Infect Immun 80:12(4398-408)2012 Dec

22977257. Kocieda VP, Adhikary S, Emig F, Yen JH, Toscano MG, Ganea D, Prostaglandin E2-induced IL-23p19 subunit is regulated by cAMP-responsive element-binding protein and C/AATT enhancer-binding protein ß in bone marrow-derived dendritic cells. J Biol Chem 287:44(36922-35)2012 Oct 26

22972984. Adhikary S, Kocieda VP, Yen JH, Tuma RF, Ganea D, Signaling through cannabinoid receptor 2 suppresses murine dendritic cell migration by inhibiting matrix metalloproteinase 9 expression. Blood 120:18(3741-9)2012 Nov 1

22139413. Delgado M, Ganea D, Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. Amino Acids :()2011 Dec 3

21970496. Adhikary S, Li H, Heller J, Skarica M, Zhang M, Ganea D, Tuma RF, Modulation of inflammatory responses by a cannabinoid-2-selective agonist after spinal cord injury. J Neurotrauma 28:12(2417-27)2011 Dec

21940623. Yen JH, Kocieda VP, Jing H, Ganea D, Prostaglandin E2 induces matrix metalloproteinase 9 expression in dendritic cells through two independent signaling pathways leading to activator protein 1 (AP-1) activation. J Biol Chem 286:45(38913-23)2011 Nov 11

21804863. Ganea D, Kocieda V, Kong W, Yen JH, Modulation of dendritic cell function by PGE2 and DHA: a framework for understanding the role of dendritic cells in neuroinflammation. Clin Lipidol 6:(277-291)2011 Jun

21587163. Toscano MG, Ganea D, Gamero AM, Cecal ligation puncture procedure. J Vis Exp :51()2011 May 7

20854895. Kong W, Yen JH, Ganea D, Docosahexaenoic acid prevents dendritic cell maturation, inhibits antigen-specific Th1/Th17 differentiation and suppresses experimental autoimmune encephalomyelitis. Brain Behav Immun 25:5(872-82)2011 Jul

20399708. Gonzalez-Rey E, Ganea D, Delgado M, Neuropeptides: keeping the balance between pathogen immunity and immune tolerance. Curr Opin Pharmacol 10:4(473-81)2010 Aug

20190134. Yen JH, Kong W, Ganea D, IFN-beta inhibits dendritic cell migration through STAT-1-mediated transcriptional suppression of CCR7 and matrix metalloproteinase 9. J Immunol 184:7(3478-86)2010 Apr 1

20122166. Kong W, Yen JH, Vassiliou E, Adhikary S, Toscano MG, Ganea D, Docosahexaenoic acid prevents dendritic cell maturation and in vitro and in vivo expression of the IL-12 cytokine family. Lipids Health Dis 9:(12)2010 Feb 1

20068554. Toscano MG, Delgado M, Kong W, Martin F, Skarica M, Ganea D, Dendritic cells transduced with lentiviral vectors expressing VIP differentiate into VIP-secreting tolerogenic-like DCs. Mol Ther 18:5(1035-45)2010 May

19531658. Yen JH, Ganea D, Interferon beta induces mature dendritic cell apoptosis through caspase-11/caspase-3 activation. Blood 114:7(1344-54)2009 Aug 13

19332079. Zhang M, Adler MW, Abood ME, Ganea D, Jallo J, Tuma RF, CB2 receptor activation attenuates microcirculatory dysfunction during cerebral ischemic/reperfusion injury. Microvasc Res 78:1(86-94)2009 Jun

19255856. Zhang M, Martin BR, Adler MW, Razdan RJ, Kong W, Ganea D, Tuma RF, Modulation of cannabinoid receptor activation as a neuroprotective strategy for EAE and stroke. J Neuroimmune Pharmacol 4:2(249-59)2009 Jun

20214038. Heller JE, Baty DE, Zhang M, Li H, Adler M, Ganea D, Gaughan J, Loftus CM, Jallo JI, Tuma RF, The combination of selective inhibition of the cannabinoid CB1 receptor and activation of the cannabinoid CB2 receptor yields improved attenuation of motor and autonomic deficits in a mouse model of spinal cord injury. Clin Neurosurg 56:(84-92)2009

18802056. Vassiliou EK, Kesler OM, Tadros JH, Ganea D, Bone marrow-derived dendritic cells generated in the presence of resolvin E1 induce apoptosis of activated CD4+ T cells. J Immunol 181:7(4534-44)2008 Oct 1

18598752. Delgado M, Ganea D, Anti-inflammatory neuropeptides: a new class of endogenous immunoregulatory agents. Brain Behav Immun 22:8(1146-51)2008 Nov

18566439. Khayrullina T, Yen JH, Jing H, Ganea D, In vitro differentiation of dendritic cells in the presence of prostaglandin E2 alters the IL-12/IL-23 balance and promotes differentiation of Th17 cells. J Immunol 181:1(721-35)2008 Jul 1

18304750. Zhang M, Martin BR, Adler MW, Razdan RK, Ganea D, Tuma RF, Modulation of the balance between cannabinoid CB(1) and CB(2) receptor activation during cerebral ischemic/reperfusion injury. Neuroscience 152:3(753-60)2008 Mar 27

19248685. Baty DE, Zhang M, Li H, Erb CJ, Adler MW, Ganea D, Loftus CM, Jallo JI, Tuma RF, Cannabinoid CB2 receptor activation attenuates motor and autonomic function deficits in a mouse model of spinal cord injury. Clin Neurosurg 55:(172-7)2008

18040812. Ganea D, Gonzalez-Rey E, Delgado M, A novel mechanism for immunosuppression: from neuropeptides to regulatory T cells. J Neuroimmune Pharmacol 1:4(400-9)2006 Dec

17925490. Yen JH, Khayrullina T, Ganea D, PGE2-induced metalloproteinase-9 is essential for dendritic cell migration. Blood 111:1(260-70)2008 Jan 1

17706916. Ganea D, Neuropeptides: active participants in regulation of immune responses in the CNS and periphery. Brain Behav Immun 22:1(33-4)2008 Jan

17665454. Sheibanie AF, Khayrullina T, Safadi FF, Ganea D, Prostaglandin E2 exacerbates collagen-induced arthritis in mice through the inflammatory interleukin-23/interleukin-17 axis. Arthritis Rheum 56:8(2608-19)2007 Aug

17548652. Sheibanie AF, Yen JH, Khayrullina T, Emig F, Zhang M, Tuma R, Ganea D, The proinflammatory effect of prostaglandin E2 in experimental inflammatory bowel disease is mediated through the IL-23-->IL-17 axis. J Immunol 178:12(8138-47)2007 Jun 15

17462790. Liu L, Yen JH, Ganea D, A novel VIP signaling pathway in T cells cAMP-->protein tyrosine phosphatase (SHP-2?)-->JAK2/STAT4-->Th1 differentiation. Peptides 28:9(1814-24)2007 Sep

16888222. Sharma V, Delgado M, Ganea D, VIP protects Th2 cells by downregulating granzyme B expression. Ann N Y Acad Sci 1070:(540-4)2006 Jul

16888178. Fernandez-Martin A, Gonzalez-Rey E, Chorny A, Martin J, Pozo D, Ganea D, Delgado M, VIP prevents experimental multiple sclerosis by downregulating both inflammatory and autoimmune components of the disease. Ann N Y Acad Sci 1070:(276-81)2006 Jul

16888172. Delgado M, Gonzalez-Rey E, Ganea D, Vasoactive intestinal peptide: the dendritic cell --> regulatory T cell axis. Ann N Y Acad Sci 1070:(233-8)2006 Jul

16888171. Delgado M, Chorny A, Ganea D, Gonzalez-Rey E, Vasoactive intestinal polypeptide induces regulatory dendritic cells that prevent acute graft versus host disease and leukemia relapse after bone marrow transplantation. Ann N Y Acad Sci 1070:(226-32)2006 Jul

16888164. Chorny A, Gonzalez-Rey E, Ganea D, Delgado M, Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo: therapeutic applications in autoimmunity and transplantation. Ann N Y Acad Sci 1070:(190-5)2006 Jul

16565493. Gonzalez-Rey E, Fernandez-Martin A, Chorny A, Martin J, Pozo D, Ganea D, Delgado M, Therapeutic effect of vasoactive intestinal peptide on experimental autoimmune encephalomyelitis: down-regulation of inflammatory and autoimmune responses. Am J Pathol 168:4(1179-88)2006 Apr

16537513. Gonzalez-Rey E, Varela N, Sheibanie AF, Chorny A, Ganea D, Delgado M, Cortistatin, an antiinflammatory peptide with therapeutic action in inflammatory bowel disease. Proc Natl Acad Sci U S A 103:11(4228-33)2006 Mar 14

16418327. Chorny A, Gonzalez-Rey E, Fernandez-Martin A, Ganea D, Delgado M, Vasoactive intestinal peptide induces regulatory dendritic cells that prevent acute graft-versus-host disease while maintaining the graft-versus-tumor response. Blood 107:9(3787-94)2006 May 1

16402407. Fernandez-Martin A, Gonzalez-Rey E, Chorny A, Ganea D, Delgado M, Vasoactive intestinal peptide induces regulatory T cells during experimental autoimmune encephalomyelitis. Eur J Immunol 36:2(318-26)2006 Feb

16397128. Gonzalez-Rey E, Chorny A, Fernandez-Martin A, Ganea D, Delgado M, Vasoactive intestinal peptide generates human tolerogenic dendritic cells that induce CD4 and CD8 regulatory T cells. Blood 107:9(3632-8)2006 May 1

16365400. Sharma V, Delgado M, Ganea D, Granzyme B, a new player in activation-induced cell death, is down-regulated by vasoactive intestinal peptide in Th2 but not Th1 effectors. J Immunol 176:1(97-110)2006 Jan 1

16301637. Delgado M, Gonzalez-Rey E, Ganea D, The neuropeptide vasoactive intestinal peptide generates tolerogenic dendritic cells. J Immunol 175:11(7311-24)2005 Dec 1

16204628. Delgado M, Chorny A, Gonzalez-Rey E, Ganea D, Vasoactive intestinal peptide generates CD4+CD25+ regulatory T cells in vivo. J Leukoc Biol 78:6(1327-38)2005 Dec

16150720. Chorny A, Gonzalez-Rey E, Fernandez-Martin A, Pozo D, Ganea D, Delgado M, Vasoactive intestinal peptide induces regulatory dendritic cells with therapeutic effects on autoimmune disorders. Proc Natl Acad Sci U S A 102:38(13562-7)2005 Sep 20

15557192. Vassiliou E, Sharma V, Jing H, Sheibanie F, Ganea D, Prostaglandin E2 promotes the survival of bone marrow-derived dendritic cells. J Immunol 173:11(6955-64)2004 Dec 1

15498767. Jing H, Yen JH, Ganea D, A novel signaling pathway mediates the inhibition of CCL3/4 expression by prostaglandin E2. J Biol Chem 279:53(55176-86)2004 Dec 31

15231725. Delgado M, Gonzalez-Rey E, Ganea D, VIP/PACAP preferentially attract Th2 effectors through differential regulation of chemokine production by dendritic cells. FASEB J 18:12(1453-5)2004 Sep

15180965. Sheibanie AF, Tadmori I, Jing H, Vassiliou E, Ganea D, Prostaglandin E2 induces IL-23 production in bone marrow-derived dendritic cells. FASEB J 18:11(1318-20)2004 Aug

15169929. Delgado M, Pozo D, Ganea D, The significance of vasoactive intestinal peptide in immunomodulation. Pharmacol Rev 56:2(249-90)2004 Jun

15020654. Delgado M, Reduta A, Sharma V, Ganea D, VIP/PACAP oppositely affects immature and mature dendritic cell expression of CD80/CD86 and the stimulatory activity for CD4(+) T cells. J Leukoc Biol 75:6(1122-30)2004 Jun

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Postdoctoral Fellows:

Jui-Hung Yen, PhD

T:  215-707-4336

Email:  jimmyyen@temple.edu  

 

Mario Skarica, MD

T: 215-707-4336

Email: mario-skarica@temple.edu

 

Miguel Garcia Toscano, PhD

T:  215-707-4336

Email:  mtoscano@temple.edu

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