Edward Harhaj, PhD
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.
- Human T-lymphotropic virus 1
- Transcription Factors
- Antiviral Agents
- Oncogene Proteins
- Adult T Cell Leukemia Lymphoma