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Personal profile

Research interests

Dr. Edward Harhaj’s research interests focus on the mechanisms of viral-induced malignancy by the human T-cell leukemia virus type 1 (HTLV-1). HTLV-1 is a retrovirus that primarily infects CD4+ T lymphocytes and is etiologically linked to adult T-cell leukemia (ATL) and an inflammatory autoimmune-like neurological disorder known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Tax is a trans-activating protein encoded by the HTLV-1 genome that regulates viral and cellular gene expression. The underlying mechanisms of Tax-mediated oncogenesis are unclear and are the primary focus of research in this laboratory. One of the main cellular targets of Tax is the NF-kB/Rel transcription factor family, an important regulator of cell growth, survival and innate and adaptive immunity. NF-kB is constitutively activated in Tax-expressing cells, HTLV-1 transformed cell lines and ATL cells. Tax requires NF-kB for the immortalization of primary T cells and ATL cells are dependent on NF-kB for their survival. Thus, determining the mechanisms of Tax-mediated activation of NF-kB as well as Tax-independent NF-kB activation in ATL is a major focus in the laboratory. Dr. Harhaj’s laboratory is currently investigating the role of autophagy and ubiquitin pathway components in Tax activation of NF-kB.

Another active area of research in the Harhaj laboratory is to elucidate the mechanisms of the negative regulation of innate antiviral signaling pathways triggered by virus infection. The RIG-I-MAVS pathway senses RNA virus infection and induces type I interferon (IFN) and cell death to restrict virus infection. The cGAS-STING pathway senses cytoplasmic DNA and induces type I IFN in response to DNA virus infection. The Harhaj laboratory seeks to understand how these signaling pathways are regulated to facilitate the inhibition of virus replication, yet not trigger excessive inflammation and tissue damage.

Education/Academic qualification

Immunobiology, Postdoctoral Training, Howard Hughes Medical Institute

… → 2001

Microbiology and Immunology, PhD, Penn State College of Medicine

… → 1999

Biology, MS, Bucknell University

… → 1994

Biology, BA, Bucknell University

… → 1992

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  • 3 Similar Profiles
Deltaretrovirus Medicine & Life Sciences
Human T-lymphotropic virus 1 Medicine & Life Sciences
Ubiquitin Medicine & Life Sciences
T-cells Chemical Compounds
T-Lymphocytes Medicine & Life Sciences
Phosphotransferases Medicine & Life Sciences
Viruses Chemical Compounds
Taxation Chemical Compounds

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Projects 2003 2019

Virus Diseases
Innate Immunity
Antiviral Agents
Cell Death
Transcription Factors

Regulation of Innate Immune Responses

Harhaj, E., Rosenblatt, J. D., Ruiz, P., Guettouche, T. & Barber, G. N.

National Institutes of Health

7/1/097/31/14

Project: Research project

Human T-lymphotropic virus 1
Antiviral Agents
Interferons
Adult T Cell Leukemia Lymphoma
Interferon Type I
NF-kappa B
Inflammation
TNF Receptor-Associated Factor 6
Ubiquitin
Tumor Necrosis Factor-alpha
Human T-lymphotropic virus 1
NF-kappa B
Ubiquitin
Ubiquitination
Deltaretrovirus
T-Lymphocytes
CD40 Ligand
Neoplasms
Cellular Immunity
Cytotoxic T-Lymphocytes

Research Output 1995 2019

MEF-2 isoforms' (A-D) roles in development and tumorigenesis

Madugula, K., Mulherkar, R., Khan, Z. K., Chigbu, D. G. I., Patel, D., Harhaj, E. & Jain, P., Apr 12 2019, In : Oncotarget. 10, 28, p. 2755-2787 33 p.

Research output: Contribution to journalReview article

Open Access
MEF2 Transcription Factors
Protein Isoforms
Carcinogenesis
Transcription Factors
Histone Deacetylases
5 Citations (Scopus)

NF-κB signaling mechanisms in HTLV-1-induced adult T-cell leukemia/lymphoma

Harhaj, E. & Giam, C. Z., Sep 1 2018, In : FEBS Journal. 285, 18, p. 3324-3336 13 p.

Research output: Contribution to journalReview article

Deltaretrovirus
Adult T Cell Leukemia Lymphoma
T-cells
Viruses
Taxation
4 Citations (Scopus)

Peroxisomes support human herpesvirus 8 latency by stabilizing the viral oncogenic protein vFLIP via the MAVS-TRAF complex

Choi, Y. B., Choi, Y. & Harhaj, E., May 1 2018, In : PLoS Pathogens. 14, 5, e1007058.

Research output: Contribution to journalArticle

CASP8 and FADD-Like Apoptosis Regulating Protein
Human Herpesvirus 8
Peroxisomes
Viral Proteins
Antiviral Agents
7 Citations (Scopus)

Regnase-1, a rapid response ribonuclease regulating inflammation and stress responses

Mao, R., Yang, R., Chen, X., Harhaj, E. W., Wang, X. & Fan, Y., May 1 2017, In : Cellular and Molecular Immunology. 14, 5, p. 412-422 11 p.

Research output: Contribution to journalReview article

Ribonucleases
Inflammation
RNA-Binding Proteins
Messenger RNA
Genes
7 Citations (Scopus)

TAX1BP1 restrains virus-induced apoptosis by facilitating itch-mediated degradation of the mitochondrial adaptor MAVS

Choi, Y. B., Shembade, N., Parvatiyar, K., Balachandran, S. & Harhaj, E., Jan 1 2017, In : Molecular and cellular biology. 37, 1, e00422-16.

Research output: Contribution to journalArticle

RNA Virus Infections
Apoptosis
Viruses
Sendai virus
Virus Activation