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Patrick Hearing

Patrick Hearing Professor

Ph.D., Northwestern University, 1980

E-mail:
Office:
Fax:

patrick.hearing@stonybrook.edu
(631)632-8813
(631) 632-8891

 

Publications

Lab Members

Research

Patrick Hearing research

 My laboratory studies the human DNA tumor virus adenovirus (Ad).  Ad is an outstanding model system to study the regulation of numerous cellular processes including proliferation, gene expression, apoptosis, and host antiviral responses to infection.  Recombinant Ad vectors also are promising agents for therapeutic gene delivery for both short term and long term treatment of a variety of inherited and acquired diseases.  Ad generally causes mild infections of the respiratory and gastrointestinal tracts, but Ad infection may be severe in infants, the elderly and in immunocompromised individuals.  Our research focuses on innate antiviral responses that are elicited during the early stage of viral infection and viral mechanisms that counteract these responses.  The results provide fundamental insights into cellular and viral processes that inhibit or promote the viral replication program.

 Adenovirus induction of an interferon (IFN) response.

The Ad DNA genome is sensed by cellular pattern recognition receptors which triggers an IFN response.  IFNs are cytokines that have pleiotropic effects and play important roles in innate and adaptive immunity.  IFNs have broad antiviral properties and function by different mechanisms. Our data demonstrate that both type I IFNa and type II IFNg block wild-type Ad replication in primary human bronchial epithelial cells and normal human diploid fibroblasts.  IFNs inhibit viral gene expression and our studies focus on the mechanistic basis of this process and what IFN signaling pathway(s) is involved.  We found that IFNs promote persistent Ad infection.  Our results reveal a novel mechanism by which Ads utilize IFN signaling to suppress lytic virus replication and to promote persistent infection.  We wish to study this process in primary human T calls, a natutal reservoir for persistent Ad infection.

 Adenovirus induction of DNA damage response (DDR).

Viruses with linear, double-stranded DNA genomes, such as Ad, are sensed by the cell as damaged DNA which triggers a DDR.  The DDR severely inhibits Ad DNA replication if unabated.  Therefore, Ad has evolved multiple mechanisms to inhibit the DDR.  The Ad E4-ORF3 protein relocalizes and sequesters proteins involved in a DDR into nuclear inclusions termed tracks.  Our research focuses on how the E4-ORF3 protein functions in this process.  We found that E4-ORF3 induces the post-translational modification of cellular proteins involved in the DDR and other processes by SUMO (small ubiquitin-like modifier).  We are studying how and why E4-ORF3 induces protein SUMO modification, and using proteomic approaches to identify novel targets of E4-ORF3-induced SUMO modification.  Current results link these processes to a novel mechanism of protein degradation.

 

Selected recent references.

Bridges, R.G., Sohn, S.Y., Wright, J, Leppard, K.N. and Hearing, P. (2016). The adenovirus E4-ORF3 protein stimulates SUMOylation of general transcription factor TFII-I to direct proteasomal degradation.  mBio, e02184-15.

Zheng, Y., Stamminger, T. and Hearing, P. (2016). E2F/Rb family proteins mediate interferon induced repression of adenovirus immediate early transcription to promote persistent viral infection. PLoS Pathogens, e1005415.

Sohn, S.Y., and Hearing, P. (2016). The adenovirus E4-ORF3 protein functions as a SUMO E3 ligase for TIF-1γ sumoylation and poly-SUMO chain elongation. Proc. Natl. Acad. Sci. USA 113:6725-6730.