733 N. Broadway
Edward D. Miller Research Building
Baltimore, MD 21205
410-955-9770 - Phone
410-955-9823 - Fax
Ribonucleic acid (RNA) molecules are found not only inside, but also outside of human cells in biological fluids such as blood plasma, urine, and cerebrospinal fluid. Although normally very labile, these molecules are protected from degradation by molecular shuttles including extracellular vesicles (EV). Rapidly expanding research programs over the last several years indicate that EV and their nucleic acid cargo may provide early warning of disease, contribute to the defense against disease, and serve as models for effective therapies. Dr. Witwer's laboratory, a part of the Molecular and Comparative Pathobiology Retrovirus Lab, investigates extracellular vesicles and RNA in the context of HIV infection and inflammatory disease. Dr. Witwer is also actively assessing the effects of diet on extracellular RNA as a potential therapeutic approach.
- "Development of miRNA-based therapies to silence or purge the latent macrophage reservoir in HAND"
- "Biomarkers of the HIV-associated neurocognitive disorders: plasma and CSF miRNAs in prediction, diagnosis, and pathogenesis of HAND" (in collaboration with PI Dr. Janice Clements)
- "Circulating cellular and extracellular noncoding RNAs in HIV-1 Elite Suppression" (in collaboration with Dr. Joel Blankson)
Undergraduates and research technologists who have worked with the Witwer lab have been co-authors on seven published or submitted scientific papers over the last two years. Students in the Witwer lab have presented at various scientific conferences and include:
- Three recipients of young investigator awards from professional meetings;
- Two recipients of Provost's Undergraduate Research Awards (PURA); and
- Two Center for AIDS Research Baltimore HIV Scholars.
Local undergraduates with laboratory experience and a strong interest in HIV, RNA, or EV research are encouraged to inquire about available projects.
Ken Witwer received his undergraduate degree from Penn State University, where he studied Biochemistry and Molecular Biology, German, and International Politics. He performed undergraduate research in the laboratory of Dr. Jerry Workman. working closely with then-postdoc Dr. Michael Carrozza. Dr. Witwer earned a doctorate in the Biochemistry, Cellular and Molecular Biology Program at Johns Hopkins and received a National Science Foundation Graduate Research Fellowship. Mentored by Dr. Janice Clements, he researched innate immune responses to HIV and related lentiviruses that infect humans, non-human primates, sheep, and goats. The two major foci of his thesis were the potential host restriction factor promyelocytic leukemia protein (PML or TRIM19) and the cytokine/chemokine regulatory system, particularly during acute infection. Dr. Witwer remained at Johns Hopkins to complete a postdoctoral fellowship in microRNA biomarker research, and he joined the MCP faculty in 2011.
- Witwer KW, Sarbanes SL, Liu J, Clements JE. A plasma microRNA signature of acute lentiviral infection: biomarkers of CNS disease. AIDS. 2011; 25(17): 2057-67. PMCID: PMC3703743
- 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). PMCID: PMC3292811
- Sisk JM, Clements JE, Witwer KW. Monocyte and monocyte-derived macrophage miRNA profiles: new evidence of complicated roles in HIV-1 restriction. Viruses. 2012; 4(10):1844-64. PMCID: PMC3497032
- Witwer KW. Data submission and quality in microarray-based microRNA profiling. Clinical Chemistry. 2013; 59(2):392-400. PMID: 23358751
- McAlexander MA, Phillips MJ, Witwer KW. Comparison of Methods for miRNA Extraction from Plasma and Quantitative Recovery of RNA from Cerebrospinal Fluid. Frontiers in Genetics. 2013; 4:83. PMCID: PMC3655275
- Witwer KW*, Buzas EI, Bemis LT, Bora A, Lasser C, Lotvall J, Nolte-'t Hoen E, Piper MG, Sivaraman S, et al. Standardization of sample collection, isolation and analysis methods in extracellular vesicle research: An ISEV position paper. Journal of Extracellular Vesicles. 2013; 2:20360. PMCID: PMC3760646
- Witwer KW*, McAlexander MA, Queen SE, Adams RJ. Real-time quantitative PCR and droplet digital PCR for plant miRNAs in mammalian blood are inconsistent with general uptake of dietary miRNAs. RNA Biology. 2013; 10(7):1080-6. PMCID: PMC3849155
- Sisk JM, Witwer KW, Tarwater PM, Clements JE. SIV Replication is Directly Downregulated by Four Antiviral miRNAs. Retrovirology. 2013; 10(1):95. PMCID: PMC3766675
- Liu J, Sisk JM, Gama L, Clements JE, Witwer KW*. Expression of tristetraprolin and miRNA during SIV infection of the central nervous system. Molecular Brain. 2013; 6(1):40. PMCID: PMC3766027
- Yu IW, Espinoza DA, McAlexander MA, Witwer KW*. OpenArray profiling reveals no differential modulation of miRNA by positive and negative CD4+ T-cell immunoselection. Experimental Hematology. 2014; 42(1):11-3. PMID: 24096121