Kenneth W. Witwer | |
---|---|
Education | Johns Hopkins University, Baltimore, Maryland, United States (PhD) |
Known for | Research on extracellular vesicles and extracellular RNA |
Scientific career | |
Fields | Virology Molecular biology Nanomedicine Nanotechnology |
Institutions | Johns Hopkins University |
Doctoral advisor | Janice E. Clements |
Website | witwerlab |
Kenneth W. Witwer is an associate professor of molecular and comparative pathobiology and neurology at the Johns Hopkins University School of Medicine in Baltimore, Maryland, United States. As nominated President-Elect of the International Society for Extracellular Vesicles (ISEV), Witwer previously served as Secretary General and Executive Chair of Science and Meetings of the society. His laboratory studies extracellular vesicles (EVs), noncoding and extracellular RNA (exRNA), and enveloped viruses, including HIV and SARS-CoV-2. Witwer is the managing editor of the journal Cytotherapy and a member of the Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease. He has advised the US Environmental Protection Agency and the US National Institutes of Health and is an associate editor of the Journal of Extracellular Vesicles.
Witwer's PhD dissertation research was on retroviruses and the innate immune system responses to pathogens such as Visna virus and simian immunodeficiency virus (SIV) as models of human immunodeficiency virus (HIV), specifically regulation of microRNAs, cytokines, and the promyelocytic leukemia protein (TRIM19). He then completed a postdoctoral research project on miRNAs as biomarkers of HIV disease. [1] In 2011, Witwer joined the faculty at Johns Hopkins, and he assumed a tenure-track position in 2012. [1] His primary appointment is in the Department of Molecular and Comparative Pathobiology. He has a secondary appointment in Neurology and Neurosurgery. He is a member of the Cellular and Molecular Medicine program and the Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease at Johns Hopkins. [2] [3]
The Witwer laboratory studies the roles of EVs, exRNA, and ncRNA in HIV disease of the central nervous system and in other neurodegenerative diseases, such as Alzheimer's and Parkinson's. [4] Another focus of the group is on how inflammatory insults like cigarette smoking affect progression of disease. [5] [6] Beginning in 2013, Witwer examined the hypothesis that RNAs such as miRNAs in dietary substances could regulate endogenous genes in mammals. These studies led him and others to the conclusion that this type of regulation is unlikely to occur in normal physiology. [7] [8] [9] He subsequently served on two Scientific Advisory Panels of the US EPA and addressed the European Food Safety Authority on related questions of environmental exposure to RNA. [1]
Witwer chaired the organizing committee of the ISEV2015 annual meeting (Bethesda, United States). [10] He has since filled several leadership roles with ISEV and was nominated to the post of President-Elect in 2022. [11] Witwer has organized or co-organized workshops and other meetings on five continents. [12] [1] Responding in 2020 to the restrictions of the COVID-19 pandemic, Witwer converted a monthly journal club at Johns Hopkins into a weekly worldwide virtual event known as "Extracellular Vesicle Club." The club became an official ISEV feature in 2021. [13] He is co-Chair with Paul Robbins of the 2022 Gordon Research Conference on EVs. [14] Witwer is an associate editor of the Journal of Extracellular Vesicles and a member of the editorial boards of Clinical Chemistry and AIDS. [1] [15] He was instrumental in the founding of a second ISEV journal, the Journal of Extracellular Biology. [16]
Witwer has contributed to scientific standardization and rigor efforts. He was corresponding author in 2013 of the first position paper of the International Society for Extracellular Vesicles, on standardization of isolation and characterization of EVs in RNA studies. [17] With Clotilde Théry, he coordinated the Minimal Information for Studies of Extracellular Vesicles (MISEV2018), a consensus guidelines document for the EV field. [18] An opponent of AIDS denialism, a largely defunct movement that denied the existence of HIV or its role in causing AIDS, [19] [20] he has encouraged high standards in scientific publishing, critiquing predatory publishing and other publishing practices. [21] [22] [23] He has advocated public availability of scientific data. [24] With the emergence of COVID-19, Witwer was interviewed about the virology of the pandemic and conspiracy theories that arose around SARS-CoV-2. [25] [26] [27] [28] He is co-corresponding author of a statement by ISEV and the International Society for Gene and Cell Therapy on extracellular vesicle-based therapies for COVID-19. [29]
The human immunodeficiency viruses (HIV) are two species of Lentivirus that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, the average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype.
In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form naturally during the processes of secretion (exocytosis), uptake (endocytosis), and the transport of materials within the plasma membrane. Alternatively, they may be prepared artificially, in which case they are called liposomes. If there is only one phospholipid bilayer, the vesicles are called unilamellar liposomes; otherwise they are called multilamellar liposomes. The membrane enclosing the vesicle is also a lamellar phase, similar to that of the plasma membrane, and intracellular vesicles can fuse with the plasma membrane to release their contents outside the cell. Vesicles can also fuse with other organelles within the cell. A vesicle released from the cell is known as an extracellular vesicle.
The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.
Coinfection is the simultaneous infection of a host by multiple pathogen species. In virology, coinfection includes simultaneous infection of a single cell by two or more virus particles. An example is the coinfection of liver cells with hepatitis B virus and hepatitis D virus, which can arise incrementally by initial infection followed by superinfection.
The human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. It can be managed with treatment. Without treatment it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS).
Microparticles are particles between 0.1 and 100 μm in size. Commercially available microparticles are available in a wide variety of materials, including ceramics, glass, polymers, and metals. Microparticles encountered in daily life include pollen, sand, dust, flour, and powdered sugar.
Exosomes, ranging in size from 30 to 150 nanometers, are membrane-bound extracellular vesicles (EVs) that are produced in the endosomal compartment of most eukaryotic cells. In multicellular organisms, exosomes and other EVs are found in biological fluids including saliva, blood, urine and cerebrospinal fluid. EVs have specialized functions in physiological processes, from coagulation and waste management to intercellular communication.
CX3C motif chemokine receptor 1 (CX3CR1), also known as the fractalkine receptor or G-protein coupled receptor 13 (GPR13), is a transmembrane protein of the G protein-coupled receptor 1 (GPCR1) family and the only known member of the CX3C chemokine receptor subfamily.
Johns Hopkins Bayview Medical Center is the teaching hospital trauma center, neonatal intensive care unit, geriatrics center, and is home to the Johns Hopkins Burn Center, the only adult burn trauma in Maryland, containing about 420 beds. Located in southeast Baltimore City, Maryland, along Eastern Avenue near Bayview Boulevard, it is part of the Johns Hopkins Health System and named after its close proximity to the Chesapeake Bay. Founded in 1773 as an almshouse, it was relocated several times until its now present location in 1866. In 1925, it transitioned into several municipal hospitals, which transferred ownership to Johns Hopkins Hospital in 1984.
Microvesicles are a type of extracellular vesicle (EV) that are released from the cell membrane. In multicellular organisms, microvesicles and other EVs are found both in tissues and in many types of body fluids. Delimited by a phospholipid bilayer, microvesicles can be as small as the smallest EVs or as large as 1000 nm. They are considered to be larger, on average, than intracellularly-generated EVs known as exosomes. Microvesicles play a role in intercellular communication and can transport molecules such as mRNA, miRNA, and proteins between cells.
CD63 antigen is a protein that, in humans, is encoded by the CD63 gene. CD63 is mainly associated with membranes of intracellular vesicles, although cell surface expression may be induced.
Gladstone Institutes is an independent, non-profit biomedical research organization whose focus is to better understand, prevent, treat and cure cardiovascular, viral and neurological conditions such as heart failure, HIV/AIDS and Alzheimer's disease. Its researchers study these diseases using techniques of basic and translational science. Another focus at Gladstone is building on the development of induced pluripotent stem cell technology by one of its investigators, 2012 Nobel Laureate Shinya Yamanaka, to improve drug discovery, personalized medicine and tissue regeneration.
Stuart C. Ray is an American physician. He is Vice Chair of Medicine for Data Integrity and Analytics, Associate Director of the Infectious Diseases Fellowship Training Program at the Johns Hopkins School of Medicine, and a Professor in the Department of Medicine, Division of Infectious Diseases. Ray also holds appointments in Viral Oncology and the Division of Health Sciences Informatics. He is affiliated with the Institute for Computational Medicine at Johns Hopkins and is licensed to practice medicine in Maryland.
Jan Lötvall is a Swedish clinical allergist and scientist working on translational research primarily in the field of asthma. He is the former director of the Krefting Research Centre at the University of Gothenburg and is the Chief Scientific Officer of ExoCoBio.
Extracellular RNA (exRNA) describes RNA species present outside of the cells in which they were transcribed. Carried within extracellular vesicles, lipoproteins, and protein complexes, exRNAs are protected from ubiquitous RNA-degrading enzymes. exRNAs may be found in the environment or, in multicellular organisms, within the tissues or biological fluids such as venous blood, saliva, breast milk, urine, semen, menstrual blood, and vaginal fluid. Although their biological function is not fully understood, exRNAs have been proposed to play a role in a variety of biological processes including syntrophy, intercellular communication, and cell regulation. The United States National Institutes of Health (NIH) published in 2012 a set of Requests for Applications (RFAs) for investigating extracellular RNA biology. Funded by the NIH Common Fund, the resulting program was collectively known as the Extracellular RNA Communication Consortium (ERCC). The ERCC was renewed for a second phase in 2019.
The International Society for Extracellular Vesicles (ISEV) is an international scientific organization that focuses on the study of extracellular vesicles (EVs). These membrane-bound particles are released from all known cells and include exosomes, ectosomes, exophers, oncosomes, and more. Established in 2011, the society is a nonprofit organization. It is governed by an executive committee. The current president is Buzás Edit. Previous presidents were Clotilde Théry (2018-2022), Andrew Hill (2016-2018) and founding president Jan Lötvall (2011-2016). The society's journals are the Journal of Extracellular Vesicles and the Journal of Extracellular Biology. ISEV also publishes the international consensus guidelines for EV studies, the "Minimal information for studies of EVs" (MISEV).
Extracellular vesicles (EVs) are lipid bilayer-delimited particles that are naturally released from almost all types of cells but, unlike a cell, cannot replicate. EVs range in diameter from near the size of the smallest physically possible unilamellar liposome to as large as 10 microns or more, although the vast majority of EVs are smaller than 200 nm. EVs can be divided according to size and synthesis route into exosomes, microvesicles and apoptotic bodies. The composition of EVs varies depending on their parent cells, encompassing proteins, lipids, nucleic acids, metabolites, and even organelles. Most cells that have been studied to date are thought to release EVs, including some archaeal, bacterial, fungal, and plant cells that are surrounded by cell walls. A wide variety of EV subtypes have been proposed, defined variously by size, biogenesis pathway, cargo, cellular source, and function, leading to a historically heterogenous nomenclature including terms like exosomes and ectosomes.
The stem cell secretome is a collective term for the paracrine soluble factors produced by stem cells and utilized for their inter-cell communication. In addition to inter-cell communication, the paracrine factors are also responsible for tissue development, homeostasis and (re-)generation. The stem cell secretome consists of extracellular vesicles, specifically exosomes, microvesicles, membrane particles, peptides and small proteins (cytokines). The paracrine activity of stem cells, i.e. the stem cell secretome, has been found to be the predominant mechanism by which stem cell-based therapies mediate their effects in degenerative, auto-immune and/or inflammatory diseases. Though not only stem cells possess a secretome which influences their cellular environment, their secretome currently appears to be the most relevant for therapeutic use.
The Journal of Extracellular Vesicles, JEV, is a peer-reviewed open-access scientific journal of the International Society for Extracellular Vesicles (ISEV). As one of two official journals of ISEV, the other being the Journal of Extracellular Biology, JEV covers research on lipid bilayer-delimited particles known as extracellular vesicles (EVs). EVs are released from cells and include endosome-origin exosomes and plasma membrane-derived ectosomes/microvesicles. The journal was established in 2012 and is currently published by Wiley. The founding editors-in-chief were Clotilde Théry, Yong Song Gho, and Peter Quesenberry. The current editor-in-chief is Jan Lötvall.
Clotilde Théry is a professor and INSERM director of research (DR2) at Institut Curie in Paris, France. She is president of the International Society for Extracellular Vesicles (ISEV), where she previously served as founding secretary general and as editor-in-chief of the Journal of Extracellular Vesicles. She is team leader of the group "Extracellular Vesicles, Immune Responses and Cancer" within the INSERM Unit 932 on "Immunity and Cancer." Théry researches extracellular vesicles that are released by immune and tumor cells, including exosomes that originate in the multivesicular body.