פרופ' ניצה פרנקל

אמריטוס במח חקר התא ואימונולוגיה
ראש מכון במח חקר התא ואימונולוגיה
מח חקר התא ואימונולוגיה אמריטוס
ניווט מהיר:
פרופ' ניצה פרנקל
טלפון פנימי: 03-6407166
טלפון נוסף: 03-6407165
פקס: 03-6407165

CV

Education:  
1972 Ph.D.; University of Chicago, IL, USA

 

Recognition for scientific contributions:

  • Discovery of the human herpesvirus 7 (HHV-7). The virus is one of 8 different herpesviruses that infect man. HHV-7 causes grave febrile convulsions in children and it is tested in patients by medial laboratories worldwide. It is studied molecularly by many virologists.
  • First distinction between Human Herpesviruses 6A and 6B by DNA structure, epidemiology and disease association.
  • Recognition of the universal signals necessary for herpesvirus DNA packaging in the structural infectious virions.
  • Derivation of the Herpesvirus amplicon vectors, which are now employed worldwide in gene and cell therapy.
  • Identification and characterization of the virion host shutoff (vhs) mRNAse controlling both host and viral gene expression.

 

Research Interests

Molecular biology of herpesviruses that infect man; the use of viral vectors in gene therapy and vaccination. Study the herpes simplex viruses HSV-1 and HSV-2 which cause facial and genital infections, and the human Herpesviruses 6 and 7 (HHV-6 and HHV-7) which cause mild to life threatening diseases in children and in bone marrow and kidney transplantations .

 

Current research projects:

  • Molecular mechanisms of herpesvirus replication and gene expression
  • Disease associations of the lymphotropic Human herpesviruseses 6A, 6B and 7 (HHV-6A, HHV-6B and HHV-7).
  • Derivation of herpesvirus vectors towards their use in gene therapy and vaccination.
  • Molecular Virology: Studies of viral DNA replication and packaging;
  • Virus-host cell interactions including HSV-1 host shutoff by mRNA degradation;
  • HHV-6A & HHV-6B induced cell stress and suicidal functions leading to apoptosis;
  • Alternations of cellular pathways and cell cycle arrest;
  • Activation of immune response in viral infections; viral miRNAs.
  • Disease association: Collaborative studies with clinical centers concerning life threatening HHV-6B reactivation in bone marrow and kidney transplantations; Infections in children with central nervous system complications.
  • Gene therapy: Development of HSV vectors for gene therapy of brain tumors employing mouse model systems; HHV-6 vectors for Leukemia/lymphomas; HHV-6 vectors towards potential vaccination against HSV infection and HIV-1/AIDS; development of anti-cancer vaccination.

 

Selected Publications

 

Sharon E, Frenkel N. Human Herpesvirus 6A Exhibits Restrictive Propagation with Limited Activation of the Protein Kinase R-eIF2α Stress Pathway. J Virol. 91(9): e02120-16, 2017.

 

Frenkel N, Sharon E, Zeigerman H. Roseoloviruses manipulate  host cell cycle. Curr Opin Virol. 9: 162-166, 2014.

 

Sharon E, Volchek L, Frenkel N. Human Herpesvirus 6 (HHV-6) alters E2F1/Rb pathways and utilizes the E2F1 transcription factor to express viral genes. Proc Natl Acad Sci U S A 111(1):451-6, 2014.

 

Dharam Ablashi , Henri Agut ,  Roberto Alvarez-Lafuente ,  Duncan A. Clark ,  Stephen Dewhurst ,  Dario DiLuca ,  Louis Flamand ,  Niza Frenkel ,  Robert Gallo ,  Ursula A. Gompels ,  Per Höllsberg ,  Steven Jacobson ,  Mario Luppi ,  Paolo Lusso ,  Mauro Malnati ,  Peter Medveczky ,  Yasuko Mori ,  Philip E. Pellett ,  Joshua C. Pritchett ,  Koichi Yamanishi and  Tetsushi Yoshikawa .   Classification of HHV-6A and HHV-6B as distinct viruses. Arch Virol. 2014 May;159(5):863-70.

 

Niza Frenkel, Ronen Borenstein and Haim Zeigerman. Selected aspects of Herpesvirus DNA replication, cleavage/packaging and the development and use of viral amplicon vectors. Book: “From the Hallowed Halls of Herpesvirology”, John A. Blaho and Joel D. Baines Editors, World Scientific Publishing / Imperial College Press, chapter 3 p59-9 1 , 201 2 .

 

Borenstein R, Zeigerman H, Frenkel N.   The DR1 and DR6 first exon of Human Herpesvirus 6A (HHV-6A) are not required for virus replication in culture and are found deleted in virus stocks which replicate well in T cell lines. J. Virol. 84 (6) :   2648-2656,   2010.

 

Borenstein R, Frenkel N. Cloning human herpes virus 6A genome into bacterial artificial chromosomes and study of DNA replication intermediates. Proc. Natl. Acad. Sci. USA 106: 19138–19143, 2009.

 

Mlechkovich G ,   Frenkel N. Human herpesvirus 6A (HHV-6A) and HHV-6B alter E2F1/Rb pathways and E2F1 localization and cause cell cycle arrest in infected T cells. J. Virol.;81 (24) : 13499-508.

 

Frenkel N   ,   Borenstein R. Characterization of the Lymphotropic Amplicons-6 and Tamplicon-7 Vectors Derived from HHV-6 and HHV-7.Curr Gene Ther. 6 (3) :399-420, 2006.

 

Frenkel N. The History of the HSV Amplicon: From Naturally Occurring Defective  Genomes to Engineered Amplicon Vectors. Curr Gene Ther.6 (3) :277-301, 2006.

 

Barzilai A,   Zivony-Elbom I,   Sarid R,   Noah E,   Frenkel N.  The herpes simplex virus type 1 vhs-UL41 gene secures viral replication by temporarily evading apoptotic cellular response to infection: Vhs-UL41 activity might require interactions with elements of cellular mRNA degradation machinery.  J. Virol.;80 (1) :505-13, 2006.

 

Borenstein R,   Singer O,   Moseri A,   Frenkel N.  Use of amplicon-6 vectors derived from human herpesvirus 6 for efficient expression of membrane-associated and -secreted proteins in T cells. J Virol.78 (9) :4730-43, 2004.

 

Rappaport D,   Engelhard D,   Tagger G,   Or R,   Frenkel N.  Antiviral prophylaxis may prevent human herpesvirus-6 reactivation in bone marrow transplant recipients. Transpl Infect Dis. 4: 10-16, 2002.

 

Romi H   ,   Singer O   ,   Rapaport D   ,   Frenkel N   .Tamplicon 7, a novel T lymphotropic vector derived from human herpesvirus 7. J. Virol. 73: 7001-7007,1999.

 

Katsafanas, G.C., Schirmer, E.C., Wyatt, L.S. and Frenkel, N. In vitro activation of human herpesviruses 6 and 7 from latency. Proc. Natl. Acad. Sci. 93: 9788-9792, 1996.

 

Frenkel, N., Singer, O. and Kwong, A.D. The herpes simplex virus amplicon - a versatile defective virus vector. Gene Therapy. 1: S40-S46, 1994.

 

Wyatt L S, Frenkel N. Human herpesvirus 7 is a constitutive inhabitant of adult human saliva .J Virol. 66 (5) :3206-9, 1992.

 

Schirmer E C, Wyatt L S, Yamanishi K, Rodriguez W J, Frenkel N. Differentiation between two distinct classes of viruses now classified as human herpesvirus 6.   Proc Natl Acad Sci U S A. 1;88 (13) :5922-6, 1991.

 

Wyatt L S, , Balachandran N, and Frenkel N .Variations in the replication and antigenic properties of human herpesvirus 6 strains.J Infect Dis.;162 (4) :852-7, 1990.

 

Frenkel, N., E.C. Schirmer, Wyatt L,. S. Katsafanas G, Roffman, E., Danovich R.M. and June, C.H. Isolation of a new herpesvirus from human CD4+ T cells. Proc. Natl. Acad. Sci. USA. 87: 748-752, 1990.

 

Frenkel N, Schirmer E C, Katsafanas G, and June C H. T-cell activation is required for efficient replication of human herpesvirus 6.J Virol. Sep;64 (9) :4598-602, 1990.

 

Danovich RM,   Frenkel N.  Herpes simplex virus induces the replication of foreign DNA.  Mol Cell Biol. 8 (8) :3272-81, 1988.

 

Kwong AD,   Kruper JA,   Frenkel N   .Herpes simplex virus virion host shutoff function.  J Virol.;62 (3) :912-21, 1988.

 

Strom T,   Frenkel N   . Effects of herpes simplex virus on mRNA stability.  J Virol.;61 (7) :2198-207, 1987.

 

Kwong AD   ,   Frenkel N   . Herpes simplex virus infected cells contain function (s) which destabilize both host and viral mRNAs. Proc. Natl. Acad. Sci. USA. 84: 1926-1930, 1987.

 

Deiss LP,   Chou J,   Frenkel N.  Functional domains within the a sequence involved in the cleavage-packaging of herpes simplex virus DNA.J Virol.;59 (3) :605-18, 1986.

 

 

Patents 

Methods of detecting the presence of human herpesvirus-7 infection U.S. Patent 5230997 . The invention relates to the discovery of human herpesvirus-7 (HHV-7). The invention also relates to bioassays for the diagnosis of HHV-7 and its detection in biological samples and to a vaccine against human herpesvirus-7. American patent granted.

 

Lymphotropic agents and vectors. U.S. Patent 6503752. The invention relates to amplicon vectors with an HHV-6 or HHV-7 DNA replication origin, a cleavage/ packaging signal, a promoter sequence which induces expression in T cells and foreign nucleic acid sequences, exemplified by the HSV-1 Thymidine Kinase, glucocerebrosidase, insulin growth factor and antisense sequence to an oncogene active in malignant lymphatic cells. US Patent granted.

 

 

Additional patent applications under review

1. Composite oncolytic herpes virus vectors- WO 02/087625 Patent No./Publication No. US-2004-0120928 .  

 

2. Vaccination vectors derived from lymphotropic human herpes viruses 6 and 7- WO 2005/012539 EP 1660666 US-2007-0264281.

 

3. Production of BAC Vectors Carrying Viral Genomes- International Procedure Application No. IL2008/001412 Patent No./Publication No. WO 2009/053988, U.S.A. App. No. 60/982,625 .

 

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