733 N. Broadway, BRB 829
Baltimore, MD 21205
410-955-9770 - Phone
410-955-9823 - Fax
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.
Dr. Witwer's scientific interests include the innate and intrinsic immune responses to retroviral infection, both in the central nervous system (CNS) and in the periphery; the characterization of biomarkers of infection, disease, and disease stage that may also provide therapeutic targets; and the role of microRNAs in HIV control and latency. During the first few weeks of infection with HIV and related viruses, known as acute phase, the body responds to rapid viral replication with a "storm" of cytokines and chemokines that help to control the virus. These responses can also potentially damage host tissues, and they are rapidly diminished at the end of acute infection. Dr. Witwer is interested in how host microRNAs (miRNAs) contribute to regulation of innate immune responses.
MicroRNAs are short RNA oligonucleotides that bind to partially complementary sequences in gene transcripts, thereby (along with protein binding partners) effecting degradation, translation inhibition, or sequestration of the targeted transcripts. Research into miRNAs in oncology and, increasingly, in infectious diseases, has demonstrated that miRNAs are valuable biomarkers, especially when detectable in easily accessed body fluids such as plasma. miRNA-based assays are being developed to diagnose and stage specific cancers and to monitor treatment response. Dr. Witwer, Dr. Clements, and colleagues were the first to characterize a plasma miRNA signature of acute retroviral infection (AIDS, 2011). In the SIV model of HIV CNS disease, they also found that upregulation of specific circulating miRNAs during acute phase predicts progression to severe disease.
Beyond their utility as biomarkers, miRNAs may be directly involved in disease, opening the door to miRNA-based therapies. In Hepatitis C virus infection, miR-122 is required for viral replication, and an inhibitor is currently undergoing human trials. In comparison with cancer and other fields, relatively few research studies have been published on the role of miRNAs in HIV disease, although several studies suggest that several host miRNAs may directly inhibit HIV replication and thus promote HIV latency. Additional evidence for the role of miRNAs in HIV disease comes from recent findings that specific subtypes of immune cells--including several with central importance for HIV control and disease progression--contain unique constellations of miRNAs that enforce cellular identity and function. In pursuit of the contribution of miRNAs to disease processes, Drs. Witwer and Clements, along with Dr. Joel Blankson of the Department of Medicine, published the inaugural study on miRNAs of circulating blood mononuclear cells (Retrovirology, 2012). With cells from control donors, viremic HIV-positive individuals, and elite suppressors (patients who naturally control HIV replication), they discovered that miRNAs such as miRs-29, -31, -150, -181, and others separate viremic patients from elite suppressors and controls. They also uncovered evidence that miRNA profiles distinguish several classes of elite suppressor and may help to identify patients who could benefit from initiation of antiviral therapy.
· National Science Foundation Graduate Research Fellowship
· The Richard T. Johnson Young Investigator Award, International Society for Neurovirology (ISNV)
· Young Investigator Award, Conference on Retroviruses and Opportunistic Infections (CROI)
· Turock Family Foundation Award
· Several scientific meeting travel awards
Local undergraduates with laboratory experience and a strong interest in retrovirus research are encouraged to inquire about available projects.
Witwer, KW (2012). XenomiRs and miRNA homeostasis in health and disease: Evidence that diet and dietary miRNAs directly and indirectly influence circulating miRNA profiles. RNA Biology 9:9
Witwer, KW, Watson, AK, Blankson, JN, Clements, JE (2012) Relationships of PBMC microRNA expression, plasma viral load, and CD4+ T-cell count in HIV-1-infected elite suppressors and viremic patients. Retrovirology 9:5.
Witwer, KW, Sarbanes, SL, Liu, J, Clements, JE (2011) A plasma microRNA signature of acute lentiviral infection: biomarkers of CNS disease. AIDS 204:1104-1114.
Witwer, KW, Sisk, JM, Gama, L, Clements, JE (2010) MicroRNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune response. J Immunol 184:2369-2376.
Witwer, KW, Gama, L, Li, M, Bartizal, CM, Queen, SE, Varrone, JJ, Brice, AK, Graham, DR, Tarwater, PM, et al. (2009) Coordinated regulation of SIV replication and immune responses in the CNS. PLoS One 4:e8129.