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Researcher Profile

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Edward Harhaj, PhD

Edward Harhaj, PhD

Professor, Department of Microbiology and Immunology
Scientific Program:Mechanisms of Carcinogenesis
EWH110@psu.edu

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.

  • T-Lymphocytes
  • Deltaretrovirus
  • Human T-lymphotropic virus 1
  • Phosphotransferases
  • Transcription Factors
  • Ubiquitin
  • Proteins
  • Neoplasms
  • Antiviral Agents
  • Adult T Cell Leukemia Lymphoma
  • Oncogene Proteins
  • Ubiquitination

Recent Publications

2024

Kazzaz, SA, Shaikh, KA, White, J, Zhou, Q, Powell, WH & Harhaj, EW 2024, 'Phosphorylation of aryl hydrocarbon receptor interacting protein by TBK1 negatively regulates IRF7 and the type I interferon response', Journal of Biological Chemistry, vol. 300, no. 1, 105525. https://doi.org/10.1016/j.jbc.2023.105525
Kazzaz, SA, Tawil, J & Harhaj, EW 2024, 'The aryl hydrocarbon receptor-interacting protein in cancer and immunity: Beyond a chaperone protein for the dioxin receptor', Journal of Biological Chemistry, vol. 300, no. 4, 107157. https://doi.org/10.1016/j.jbc.2024.107157
Mohanty, S, Suklabaidya, S, Lavorgna, A, Ueno, T, Fujisawa, JI, Ngouth, N, Jacobson, S & Harhaj, EW 2024, 'The tyrosine kinase KDR is essential for the survival of HTLV-1-infected T cells by stabilizing the Tax oncoprotein', Nature communications, vol. 15, no. 1, 5380. https://doi.org/10.1038/s41467-024-49737-5

2023

Mohanty, S & Harhaj, EW 2023, 'Mechanisms of Innate Immune Sensing of HTLV-1 and Viral Immune Evasion', Pathogens, vol. 12, no. 5, 735. https://doi.org/10.3390/pathogens12050735

2022

White, J, Suklabaidya, S, Vo, MT, Choi, YB & Harhaj, EW 2023, 'Multifaceted roles of TAX1BP1 in autophagy', Autophagy, vol. 19, no. 1, pp. 44-53. https://doi.org/10.1080/15548627.2022.2070331
Madugula, KK, Joseph, J, DeMarino, C, Ginwala, R, Teixeira, V, Khan, ZK, Sales, D, Wilson, S, Kashanchi, F, Rushing, AW, Lemasson, I, Harhaj, EW, Janakiram, M, Hilda Ye, B & Jain, P 2022, 'Regulation of human T-cell leukemia virus type 1 antisense promoter by myocyte enhancer factor-2C in the context of adult T-cell leukemia and lymphoma', Haematologica, vol. 107, no. 12, pp. 2928-2943. https://doi.org/10.3324/haematol.2021.279542

2020

Harhaj, EW & Shembade, N 2020, 'Lymphotropic viruses: Chronic inflammation and induction of cancers', Biology, vol. 9, no. 11, 390, pp. 1-15. https://doi.org/10.3390/biology9110390
Mohanty, S & Harhaj, EW 2020, 'Mechanisms of oncogenesis by HTLV-1 tax', Pathogens, vol. 9, no. 7, 543, pp. 1-28. https://doi.org/10.3390/pathogens9070543
Mohanty, S, Han, T, Choi, YB, Lavorgna, A, Zhang, J & Harhaj, EW 2020, 'The E3/E4 ubiquitin conjugation factor UBE4B interacts with and ubiquitinates the HTLV-1 Tax oncoprotein to promote NF-κB activation', PLoS pathogens, vol. 16, no. 12, e1008504. https://doi.org/10.1371/journal.ppat.1008504