|Department Affiliations||Department of Molecular and Comparative Pathobiology, Johns Hopkins Institute for NanoBioTechnology|
|SOM Address||829 Miller Research Building|
The Witwer laboratory investigates noncoding RNAs and extracellular vesicles in HIV infection and inflammatory disease. Noncoding RNAs such as microRNAs play regulatory roles in the cell. They are also released into the extracellular environment, where, protected inside molecular carriers extracellular vesicles, they may travel and signal to distant cells and serve as biomarkers of the state of the cell of origin.
Newly funded graduate position
In 2015, we received a five-year grant from the National Institute on Drug Abuse to study the immunomodulatory role of extracellular vesicles in persistent HIV-associated inflammation of smoking and non-smoking populations. Although anti-HIV drugs are highly effective at reducing virus replication and preventing death, people living with HIV still experience higher-than-expected rates of numerous non-AIDS diseases, a result of factors such as persistent inflammation and immune activation. Substance abuse, including smoking cigarettes, can aggravate these conditions by contributing to inflammation. Extracellular vesicles (“exosomes,” “microvesicles,” and others) are the great communicators of the body, shuttling messages from cell to cell. In this project, we investigate how these particles and their messages are involved in the immune dysfunction of HIV infection and cigarette abuse, looking for ways to harness the power of extracellular vesicles to prevent damage.
Additional projects in the lab
- Using gene editing machinery to stimulate HIV production
- Targeting nuclear small RNAs to reverse HIV latency
- Investigating roles of tRNA fragments and other non-canonical small RNAs in HIV infection
- Extracellular RNA in diagnosis of HIV-associated central nervous system disease
- Cataloging direct targets of miRNA in specific cell types and conditions
Selected techniques and resources
- Nanoparticle tracking
- Electron microscopy (EM) and immunogold EM
- quantitative PCR and qPCR arrays
- Primary cell culture
- In vitro models
- Access to in vivo models and archived samples
- Fluorescence and confocal microscopy
- Physiologic oxygen incubator
- Access to BSL2 and BSL2/3 facilties
- Tosar JP, Gámbaro F, Sanguinetti J, Bonilla B, Witwer KW, Cayota A: Assessment of small RNA sorting into different extracellular fractions revealed by high-throughput sequencing of breast cell lines. Nucleic Acids Research 2015, 43(11):5601-16.
- Muth DC, McAlexander MA, Ostrenga LJ, Pate NM, Izzi JM, Adams RJ, Pate KA, Beck SE, Karim BO, Witwer KW: Potential role of cervicovaginal extracellular particles in diagnosis of endometriosis. BMC Veterinary Research 2015, 11:187.
- Eitan E, Zhang S, Witwer KW, Mattson MP. Extracellular vesicle-depleted fetal bovine and human sera have reduced capacity to support cell growth. Journal of Extracellular Vesicles 2015, 4:26373.
- Witwer KW, Buzas EI, Bemis LT, Bora A, Lasser C, Lotvall J, Nolte-‘t Hoen EN, Piper MG, Sivaraman S, Skog J et al: Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. Journal of Extracellular Vesicles 2013, 2.
- Witwer KW, Watson AK, Blankson JN, Clements JE: Relationships of PBMC microRNA expression, plasma viral load, and CD4+ T-cell count in HIV-1-infected elite suppressors and viremic patients. Retrovirology 2012, 9:5.
- Witwer KW, Sarbanes SL, Liu J, Clements JE: A plasma microRNA signature of acute lentiviral infection: biomarkers of CNS disease. AIDS 2011, 204(7):1104-1114.