Department of Molecular and Comparative Pathobiology - Retrovirus Laboratory
Cellular and Molecular Medicine (http://cmm.jhmi.edu/)
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 quite labile, some RNA molecules are protected from degradation by molecular shuttles including extracellular vesicles (EV). These 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 investigates extracellular vesicles and RNA in the context of HIV infection, inflammatory disease, and other conditions. Related research interests include retrovirus restriction factors and therapeutic delivery of RNA.
- Board of the International Society for Extracellular Vesicles: member-at-large and chair of the local organizing committee, ISEV 2015
- Ad hoc reviewer for >30 scientific journals
- Grant review for NIDDK and the Dutch Technology Foundation STW Grant Program
- Johns Hopkins Postdoctoral Affairs Advisory Committee
- Organizer, “Exosome Research Workshop” (February, 2014) and a microRNA-themed journal club (with Marc Halushka, Sam Das)
- Panelist, US Environmental Protection Agency: Federal Insecticide, Fungicide, and Rodenticide Act Scientific Advisory Panel (FIFRA-SAP) on RNAi technology as a pesticide (2014) (http://www.epa.gov/scipoly/sap/meetings/2014/january/012814minutes.pdf)
Funded projects (selected):
- R21 AI102659, "Circulating cellular and extracellular noncoding RNAs in HIV-1 Elite Suppression" (with Dr. Joel Blankson)
- Johns Hopkins University Center for AIDS Research (1P30AI094189) faculty development award, “Cervicovaginal exosomes and extracellular RNA in HIV infection and resistance”
- NIMH Center pilot grant, "Development of miRNA-based therapies to silence or purge the latent macrophage reservoir in HAND"
- R01 NS076357, "Biomarkers of the HIV-associated neurocognitive disorders: plasma and CSF miRNAs in prediction, diagnosis, and pathogenesis of HAND" (PI: Dr. Janice Clements)
Mentees and research opportunities
Dr. Witwer is a faculty member of the Cellular and Molecular Medicine graduate program (http://cmm.jhmi.edu/). Undergraduates and research technologists in the Witwer lab have been co-authors on eight published or submitted journal articles. Students have presented at scientific conferences and received young investigator awards, Provost's Undergraduate Research Awards (PURA), a Dean’s Undergraduate Research Award (DURA), Center for AIDS Research Baltimore HIV Scholars summer awards, and the Second Decade Society scholarship. Students with laboratory experience and a strong interest in HIV, RNA, or EV research are encouraged to inquire about available projects.
Dr. Witwer performed undergraduate research in the laboratory of Dr. Jerry Workman, working closely with Dr. Michael Carrozza. Dr. Witwer earned a doctorate in the Biochemistry, Cellular and Molecular Biology Program at Johns Hopkins, supported by 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. 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