Melanie Ott, MD, PhD

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

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: 

Evaluating a New Class of AKT/mTOR Activators for HIV Latency Reversing Activity Ex Vivo and In Vivo.

Journal of virology

Gramatica A, Schwarzer R, Brantley W, Varco-Merth B, Sperber HS, Hull PA, Montano M, Migueles SA, Rosenthal D, Hogan LE, Johnson JR, Packard TA, Grimmett ZW, Herzig E, Besnard E, Nekorchuk M, Hsiao F, Deeks SG, Snape M, Kiernan B, Roan NR, Lifson JD, Estes JD, Picker LJ, Verdin E, Krogan NJ, Henrich TJ, Connors M, Ott M, Pillai SK, Okoye AA, Greene WC

Tropism of SARS-CoV-2 for Developing Human Cortical Astrocytes.

bioRxiv : the preprint server for biology

Andrews MG, Mukhtar T, Eze UC, Simoneau CR, Perez Y, Mostajo-Radji MA, Wang S, Velmeshev D, Salma J, Kumar GR, Pollen AA, Crouch EE, Ott M, Kriegstein AR

Novel RT-ddPCR Assays for determining the transcriptional profile of SARS-CoV-2.

bioRxiv : the preprint server for biology

Telwatte S, Kumar N, Vallejo-Gracia A, Kumar GR, Lu CM, Ott M, Wong JK, Yukl SA

Author Correction: Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+ macrophages.

Nature Metabolism

Covarrubias AJ, Kale A, Perrone R, Lopez-Dominguez JA, Pisco AO, Kasler HG, Schmidt MS, Heckenbach I, Kwok R, Wiley CD, Wong HS, Gibbs E, Iyer SS, Basisty N, Wu Q, Kim IJ, Silva E, Vitangcol K, Shin KO, Lee YM, Riley R, Ben-Sahra I, Ott M, Schilling B, Scheibye-Knudsen M, Ishihara K, Quake SR, Newman J, Brenner C, Campisi J, Verdin E

Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses.

Cell

Wang R, Simoneau CR, Kulsuptrakul J, Bouhaddou M, Travisano KA, Hayashi JM, Carlson-Stevermer J, Zengel JR, Richards CM, Fozouni P, Oki J, Rodriguez L, Joehnk B, Walcott K, Holden K, Sil A, Carette JE, Krogan NJ, Ott M, Puschnik AS