Dirk P Dittmer
University of North Carolina at Chapel Hill, NC·Microbiology & Immunology
Roughly one in five cancers worldwide is caused by an infectious agent, and most of those are viruses. Two closely related herpesviruses are central to this lab's work: Epstein-Barr virus (EBV), tied to lymphomas and to cancers of the nose, throat and stomach, and Kaposi sarcoma-associated herpesvirus (KSHV), which causes Kaposi sarcoma (KS) and certain lymphomas and is a leading cause of cancer in people living with HIV.
- Fields
Microbiology & Immunology
Genetics
Medicine & Clinical Research
- Topics
Kaposi sarcoma
Epstein-Barr virus
gammaherpesvirus
- Grants
- 6 known grants, through Aug 2029
What they work on
- Develop fully immunocompetent transgenic mice carrying the complete Epstein-Barr virus genome to model EBV-driven epithelial cancers such as nasopharyngeal and gastric carcinoma, and test the in vivo roles of EBV transcription, microRNAs and proteins.
- Derive new cell lines to screen small molecules against evolutionarily conserved virus-host interactions, providing a preliminary filter that reduces animal use in EBV tumor studies.
- Build a virus purification pipeline that uses 50-500 mL samples of urine, stool, saliva or blood to reach sensitivity below one viral genome copy per milliliter for human virome sequencing.
- Create a single-virion detection method yielding viral direct counts, so next-generation sequencing results can be anchored to how many intact virus particles a sample actually contains.
- Identify new drug targets feeding into the PI3K/Akt/mTOR growth-signaling pathway that KSHV-associated Kaposi sarcoma and primary effusion lymphoma depend on, using CRISPR screens, novel compounds and combination strategies.
- Define how antiretroviral therapy affects KSHV oral transmission, oral and systemic Kaposi sarcoma, and the latent viral reservoir, and find biomarkers for therapy selection using one of the largest KS clinical trial sample collections.
- Test whether KSHV-derived extracellular vesicles carrying viral microRNAs reprogram the Kaposi sarcoma tumor environment and influence neighboring EBV-infected cells in lymph nodes.
- Image individual extracellular vesicles by super-resolution microscopy and cryo-electron microscopy, and explore repurposing natural vesicles as carriers for targeted Kaposi sarcoma therapy.
More about the research
Across its projects, the lab asks how these viruses reshape the cells and tissues around them, how to build better laboratory models of the resulting tumors, which drugs those tumors depend on, and how to count viruses in human samples accurately.
Why it matters
Kaposi sarcoma is the most common cancer in people living with HIV, in the United States and especially in sub-Saharan Africa, and EBV-driven lymphomas and stomach and nasopharyngeal cancers affect people worldwide. Identifying drug targets already in human safety testing, new biomarkers to match patients to therapy, and the first immunocompetent mouse model of EBV-driven solid tumors could speed drug and vaccine development for these cancers. Better tools to purify and count virus particles could also put human virome measurements on a common footing.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Neelam Sharma-Walia
Rosalind Franklin University of Medicine and Science, IL·Microbiology & Immunology
Determine how KSHV infection turns up the host protein nucleolin and whether nucleolin is needed to keep the virus in its quiet latent state, studying infected endothelial cells and primary effusion lymphoma cells.
Paul Lieberman
University of Pennsylvania, PA·Microbiology & Immunology
Test whether EBV reshapes the host low-oxygen response during primary infection to keep infected cells alive, examining how the viral proteins EBNA1 and EBNA2 bind and regulate host hypoxia genes including HIF1A.
Shannon Kenney
University of Wisconsin-Madison, WI·Microbiology & Immunology
Test whether primary human germinal center B cells infected with the lab's EBNA2-deleted EBV mutant, with or without MYC overexpression, form Burkitt-, Hodgkin- or diffuse large B cell lymphoma-like tumors in immunodeficient NSG mice.
The school
University of North Carolina at Chapel Hill: 72 labs on PI Pages, $1.6B a year on research, 523 research doctorates a year.
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