Melanie Ott, MD, PhD

Senior Investigator, Gladstone Institute of Virology and Immunology
Professor
Department of Medicine
+1 415 734-4807

My laboratory is interested in the molecular mechanisms of viral pathogenesis. We focus on two viruses: HIV-1 and Hepatitis C Virus (HCV). Both are important public health problems and share common traits including high propensities to establish chronic infections and a lack of efficient vaccines. Our HIV efforts focus on viral transcription and latency as remaining barriers to viral eradication. We focus specifically on posttranslational modifications of the HIV transactivator Tat as potential targets to manipulate viral transcription therapeutically. In the past, we defined Tat acetylation and deacetylation as important steps in the Tat transactivation cycle and recently identified acetylation of the RNA polymerase II as an important regulatory step in transcription elongation. We are also interested in Tat-host cell interactions, specifically how Tat expression in infected T cells dysregulates immune functions and supports a premature aging syndrome observed in HIV+ individuals. Our HCV research focuses on the interaction of viral proteins with intracellular lipid droplets. These organelles play a critical role in the assembly of HCV progeny virions and are occupied in infected cells by the HCV nucleocapsid core. We recently showed that core interacts with the triglyceride-synthesizing enzyme DGAT1, and that this interaction plays a central role in the recruitment of core to lipid droplets. We are currently defining the role of lipid droplets in related viruses such as Dengue and Zika Virus and performed a comprehensive protein:protein interaction analysis of HCV proteins and hepatoma cells, which identified many novel factors involved in the infection. Both, HCV and HIV research in my laboratory includes replication studies with infectious viral clones, which are performed in the BSL3 laboratory. Recent rotation projects in the lab:

  • defining the interaction of Dengue virus with lipid droplets
  • characterizing a new posttranslational modification of Tat at lysine 71
  • validating interaction partners of SIRT1 in T cells
Primary Thematic Area: 
Virology & Microbial Pathogenesis
Secondary Thematic Area: 
Immunology
Research Summary: 
Molecular Pathogenesis of HIV and Hepatitis C Virus Infections

Websites

Publications: 

The Short Isoform of BRD4 Promotes HIV-1 Latency by Engaging Repressive SWI/SNF Chromatin-Remodeling Complexes.

Molecular cell

Conrad RJ, Fozouni P, Thomas S, Sy H, Zhang Q, Zhou MM, Ott M

SMYD2-Mediated Histone Methylation Contributes to HIV-1 Latency.

Cell host & microbe

Boehm D, Jeng M, Camus G, Gramatica A, Schwarzer R, Johnson JR, Hull PA, Montano M, Sakane N, Pagans S, Godin R, Deeks SG, Krogan NJ, Greene WC, Ott M

The mTOR Complex Controls HIV Latency.

Cell host & microbe

Besnard E, Hakre S, Kampmann M, Lim HW, Hosmane NN, Martin A, Bassik MC, Verschueren E, Battivelli E, Chan J, Svensson JP, Gramatica A, Conrad RJ, Ott M, Greene WC, Krogan NJ, Siliciano RF, Weissman JS, Verdin E

Retrovirus Integration: Some Assembly Required?

Cell host & microbe

Ali I, Conrad RJ, Ott M

Salicylate, diflunisal and their metabolites inhibit CBP/p300 and exhibit anticancer activity.

eLife

Shirakawa K, Wang L, Man N, Maksimoska J, Sorum AW, Lim HW, Lee IS, Shimazu T, Newman JC, Schröder S, Ott M, Marmorstein R, Meier J, Nimer S, Verdin E