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Francesca Peruzzi, PhD

Associate Professor, Neuroscience

Associate Professor, Neurovirology

Location: Room 749 MERB

Telephone:  215-707-5823

Fax:  215-707-4888

Email: fperuzzi@temple.edu

Department of Neuroscience

Center for Neurovirology

PhD, Biology - 1992

University of Siena

Siena, Italy

 

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The major emphasis rests on studying signal transduction in the CNS. Studies are currently in progress to develop stem cell technology for treatment of CNS disorders.

Research Summary
HIV-1 invasion of the central nervous system (CNS) induces a variety of clinical abnormalities including dementia, also known as HIV-1 associated dementia (HAD). Histologically, brain biopsy from AIDS patients with neurological disorders exhibit a broad range of abnormalities, most notably neuronal cell loss. The absence of neuronal infection suggested an indirect role for the virus to induce neuronal cell damage. Results from a large number of studies indicated that expression and secretion of several cellular proteins including cytokines and immunomodulators from the infected macrophages, microglia, and astrocytes in the brain participate in neuronal cell damage. In addition to cellular factors, the viral regulatory protein Tat has received attention due to its unique ability to be secreted by the infected cells, enter into uninfected cells and alter the expression of cellular genes in the absence of viral infection. Moreover, Tat protein has been shown to have neurotoxic activity, most likely through dysregulating signaling pathways that are critical for neuronal cell survival. By using a PC12 neuronal cell model, as well as primary rat neuronal cells, we demonstrated that Tat stimulates the expression of the Id gene, a known cellular protein that inhibits differentiation of neuronal cells. Id, by affecting expression and activity of several factors which control the cell cycle promotes unscheduled entering of quiescent cells into proliferating stage and that results in suppression of a group of proteins that are implicated in the maintenance of differentiated cells. The basic helix-loop-helix, bHLH, family of DNA binding proteins such as Ngn, NeuroD, and MashI, are the primary targets for Id1 which upon dysregulation may promote neuronal cell injury and apoptosis. Our preliminary data have suggested that activation of the Id1 gene by Tat is mediated via a novel regulatory pathway that includes critical transcription factors such as Egr1, C/EBP, and SP1, all of which physically and functionally interact with Tat. We have performed a series of comprehensive functional and structural studies to unravel the molecular mechanisms involved in activation of Id1 by Tat in neuronal cells. In another series of studies we have investigated the importance of Id1, whose expression is elevated by Tat in the neuronal cell cycle, control of expression and activity of factors controlling cell entry into the cell cycle and checkpoints such as p21, p16, pRb, and various cyclins. Furthermore, the role of Tat-induced overproduction of Id1 on expression and activity of bHLH will be assessed. The outcome of these studies will provide new information on the pathways which are affected by HIV-1 Tat and will assist to improve our effort to develop strategies against HIV-1 induced neuronal cell injury.

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

19834489. Gualco E, Urbanska K, Perez-Liz G, Sweet T, Peruzzi F, Reiss K, Del Valle L, IGF-IR-dependent expression of Survivin is required for T-antigen-mediated protection from apoptosis and proliferation of neural progenitors. Cell Death Differ :()2009 Oct 16

19273072. Gualco E, Wang JY, Del Valle L, Urbanska K, Peruzzi F, Khalili K, Amini S, Reiss K, IGF-IR in neuroprotection and brain tumors. Front Biosci 14:(352-75)2009 Jan 1

19022302. Passiatore G, Rom S, Eletto D, Peruzzi F, HIV-1 Tat C-terminus is cleaved by calpain 1: implication for Tat-mediated neurotoxicity. Biochim Biophys Acta 1793:2(378-87)2009 Feb

18381601. Eletto D, Russo G, Passiatore G, Del Valle L, Giordano A, Khalili K, Gualco E, Peruzzi F, Inhibition of SNAP25 expression by HIV-1 Tat involves the activity of mir-128a. J Cell Physiol 216:3(764-70)2008 Sep

18247371. Darbinian N, Darbinyan A, Czernik M, Peruzzi F, Khalili K, Reiss K, Gordon J, Amini S, HIV-1 Tat inhibits NGF-induced Egr-1 transcriptional activity and consequent p35 expression in neural cells. J Cell Physiol 216:1(128-34)2008 Jul

17593555. Wang JY, Gualco E, Peruzzi F, Sawaya BE, Passiatore G, Marcinkiewicz C, Staniszewska I, Ferrante P, Amini S, Khalili K, Reiss K, Interaction between serine phosphorylated IRS-1 and beta1-integrin affects the stability of neuronal processes. J Neurosci Res 85:11(2360-73)2007 Aug 15

16741963. Darbinian-Sarkissian N, Czernik M, Peruzzi F, Gordon J, Rappaport J, Reiss K, Khalili K, Amini S, Dysregulation of NGF-signaling and Egr-1 expression by Tat in neuronal cell culture. J Cell Physiol 208:3(506-15)2006 Sep

16611822. Aprea S, Del Valle L, Mameli G, Sawaya BE, Khalili K, Peruzzi F, Tubulin-mediated binding of human immunodeficiency virus-1 Tat to the cytoskeleton causes proteasomal-dependent degradation of microtubule-associated protein 2 and neuronal damage. J Neurosci 26:15(4054-62)2006 Apr 12

16307448. Wang JY, Grabacka M, Marcinkiewicz C, Staniszewska I, Peruzzi F, Khalili K, Amini S, Reiss K, Involvement of alpha1beta1 integrin in insulin-like growth factor-1-mediated protection of PC12 neuronal processes from tumor necrosis factor-alpha-induced injury. J Neurosci Res 83:1(7-18)2006 Jan

16235026. Saunders M, Eldeen MB, Del Valle L, Reiss K, Peruzzi F, Mameli G, Gelman BB, Khalili K, Amini S, Sawaya BE, p73 modulates HIV-1 Tat transcriptional and apoptotic activities in human astrocytes. Apoptosis 10:6(1419-31)2005 Dec

16146763. Peruzzi F, The multiple functions of HIV-1 Tat: proliferation versus apoptosis. Front Biosci 11:(708-17)2006 Jan 1

15936090. Peruzzi F, Bergonzini V, Aprea S, Reiss K, Sawaya BE, Rappaport J, Amini S, Khalili K, Cross talk between growth factors and viral and cellular factors alters neuronal signaling pathways: implication for HIV-associated dementia. Brain Res Brain Res Rev 50:1(114-25)2005 Dec 1

15595625. Wang JY, Del Valle L, Peruzzi F, Trojanek J, Giordano A, Khalili K, Reiss K, Polyomaviruses and cancer--interplay between viral proteins and signal transduction pathways. J Exp Clin Cancer Res 23:3(373-83)2004 Sep

15361847. Bergonzini V, Delbue S, Wang JY, Reiss K, Prisco M, Amini S, Khalili K, Peruzzi F, HIV-Tat promotes cellular proliferation and inhibits NGF-induced differentiation through mechanisms involving Id1 regulation. Oncogene 23:46(7701-11)2004 Oct 7

14755242. Chipitsyna G, Slonina D, Siddiqui K, Peruzzi F, Skorski T, Reiss K, Sawaya BE, Khalili K, Amini S, HIV-1 Tat increases cell survival in response to cisplatin by stimulating Rad51 gene expression. Oncogene 23:15(2664-71)2004 Apr 8

14559999. Trojanek J, Ho T, Del Valle L, Nowicki M, Wang JY, Lassak A, Peruzzi F, Khalili K, Skorski T, Reiss K, Role of the insulin-like growth factor I/insulin receptor substrate 1 axis in Rad51 trafficking and DNA repair by homologous recombination. Mol Cell Biol 23:21(7510-24)2003 Nov

12504542. Ying Wang J, Peruzzi F, Lassak A, Del Valle L, Radhakrishnan S, Rappaport J, Khalili K, Amini S, Reiss K, Neuroprotective effects of IGF-I against TNFalpha-induced neuronal damage in HIV-associated dementia. Virology 305:1(66-76)2003 Jan 5

12491166. Del Valle L, Wang JY, Lassak A, Peruzzi F, Croul S, Khalili K, Reiss K, Insulin-like growth factor I receptor signaling system in JC virus T antigen-induced primitive neuroectodermal tumors--medulloblastomas. J Neurovirol 8 Suppl 2:(138-47)2002 Dec

12491158. Peruzzi F, Gordon J, Darbinian N, Amini S, Tat-induced deregulation of neuronal differentiation and survival by nerve growth factor pathway. J Neurovirol 8 Suppl 2:(91-6)2002 Dec

11877394. Lassak A, Del Valle L, Peruzzi F, Wang JY, Enam S, Croul S, Khalili K, Reiss K, Insulin receptor substrate 1 translocation to the nucleus by the human JC virus T-antigen. J Biol Chem 277:19(17231-8)2002 May 10

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