Sean Whelan (scientist)

Last updated

Professor

Sean P.J. Whelan

Ph.D.
Sean Whelan.2019.jpg
Sean Whelan in 2019
Born1967
Leeds, England
CitizenshipUS and UK
Alma materUniversity of Birmingham, England
Scientific career
Institutions Harvard Medical School
Washington University in St. Louis
Thesis Alteration of the Cellular Binding Characteristics of Poliovirus (1993)
Doctoral advisor Jeffrey Almond, University of Reading
Other academic advisorsGail Wertz, University of Alabama
Website http://www.whelan-lab.org/

Sean Whelan is a British-American virologist. He is known for identifying the cellular protein used as a receptor by Ebola virus, [1] [2] [3] for defining the entry pathway that rabies virus uses to enter neurons, [4] and for identifying the ribosome as a possible target for antiviral drugs. [5] [6] In July 2019, he was announced as the new Chair of the Department of Molecular Microbiology at Washington University School of Medicine in St Louis, Missouri. [7] [8] In February 2020, Whelan was recognized as the LGBTQ+ Scientist of the Year 2020 by the National Organization of Gay and Lesbian Scientists and Technical Professionals. [9] [10]

Contents

Education

Whelan received a First Class Honors degree in Microbiology and Biochemistry from the University of Birmingham. He performed his PhD work with noted virologist Jeffrey Almond, then at the University of Reading.

Career

Whelan joined Harvard Medical School's Department of Microbiology and Molecular Genetics in 2002. He was promoted to Professor of Microbiology and Immunobiology in 2012. He served as head of Harvard's PhD Program in Virology, [11] and directed an NIH-funded Center for Excellence in Translational Research. [12] In July 2019, Washington University in St. Louis announced that Whelan had been named Chair of the Department of Molecular Microbiology and the Marvin A. Brennecke Distinguished Professor of Microbiology at Washington University School of Medicine. [13]

Whelan's research focuses on using Vesicular Stomatitis Virus (VSV) as a model system for negative-sense single-stranded RNA viruses such as the rabies, measles and Ebola viruses. He began this work as a post-doc in the laboratory of Professor Gail Wertz, developing a system for expressing infectious VSV particles from cDNA clones, [14] which led to a patent on VSV-based gene therapy vectors and vaccines. [15] VSV pseudotypes, which carry the envelope proteins of other viruses, are useful tools for studying the behavior of pathogenic viruses. [16] Whelan has used this approach to study the entry process of Ebola, [17] to identify the cellular protein the virus uses as a receptor, [1] [2] [3] and to study how the rabies virus infects neurons. [4]

Whelan also studies the viral life cycle of VSV to identify potential antiviral targets. [5] [18] He identified a specific subunit of the ribosome, RPL40, as being essential to initiate translation of VSV mRNAs. [6] This selective mechanism allows the virus to block translation of host mRNAs without preventing the production of its own proteins. Interfering with this mechanism could lead to antiviral therapies. [5] With Stephen C. Harrison, he used cryo-EM to determine the structure of the L protein of VSV, [19] revealing several potential drug targets. [18]

Advocacy

As a founding member of the group "Scientists for Science", [20] Whelan has argued that research into infectious pathogens is "essential for a comprehensive understanding of microbial disease pathogenesis, prevention and treatment", and that further regulation of work on dangerous pathogens should only be considered in the context of "input from outside experts with the background and skills to conduct actual risk assessments based on specific experiments and existing laboratories". [21]

Awards

Related Research Articles

<span class="mw-page-title-main">RNA virus</span> Subclass of viruses

An RNA virus is a virus—other than a retrovirus—that has ribonucleic acid (RNA) as its genetic material. The nucleic acid is usually single-stranded RNA (ssRNA) but it may be double-stranded (dsRNA). Notable human diseases caused by RNA viruses include the common cold, influenza, SARS, MERS, Covid-19, Dengue Virus, hepatitis C, hepatitis E, West Nile fever, Ebola virus disease, rabies, polio, mumps, and measles.

<i>Filoviridae</i> Family of viruses in the order Mononegavirales

Filoviridae is a family of single-stranded negative-sense RNA viruses in the order Mononegavirales. Two members of the family that are commonly known are Ebola virus and Marburg virus. Both viruses, and some of their lesser known relatives, cause severe disease in humans and nonhuman primates in the form of viral hemorrhagic fevers.

<span class="mw-page-title-main">Polysome</span> Ribosomes bound to an mRNA molecule

A polyribosome is a group of ribosomes bound to an mRNA molecule like “beads” on a “thread”. It consists of a complex of an mRNA molecule and two or more ribosomes that act to translate mRNA instructions into polypeptides. Originally coined "ergosomes" in 1963, they were further characterized by Jonathan Warner, Paul M. Knopf, and Alex Rich.

<i>Indiana vesiculovirus</i> Species of virus

Indiana vesiculovirus, formerly Vesicular stomatitis Indiana virus is a virus in the family Rhabdoviridae; the well-known Rabies lyssavirus belongs to the same family. VSIV can infect insects, cattle, horses and pigs. It has particular importance to farmers in certain regions of the world where it infects cattle. This is because its clinical presentation is identical to the very important foot and mouth disease virus.

<i>Rhabdoviridae</i> Family of viruses in the order Mononegavirales

Rhabdoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Vertebrates, invertebrates, plants, fungi and protozoans serve as natural hosts. Diseases associated with member viruses include rabies encephalitis caused by the rabies virus, and flu-like symptoms in humans caused by vesiculoviruses. The name is derived from Ancient Greek rhabdos, meaning rod, referring to the shape of the viral particles. The family has 40 genera, most assigned to three subfamilies.

<span class="mw-page-title-main">Defective interfering particle</span>

Defective interfering particles (DIPs), also known as defective interfering viruses, are spontaneously generated virus mutants in which a critical portion of the particle's genome has been lost due to defective replication or non-homologous recombination. The mechanism of their formation is presumed to be as a result of template-switching during replication of the viral genome, although non-replicative mechanisms involving direct ligation of genomic RNA fragments have also been proposed. DIPs are derived from and associated with their parent virus, and particles are classed as DIPs if they are rendered non-infectious due to at least one essential gene of the virus being lost or severely damaged as a result of the defection. A DIP can usually still penetrate host cells, but requires another fully functional virus particle to co-infect a cell with it, in order to provide the lost factors.

Pseudotyping is the process of producing viruses or viral vectors in combination with foreign viral envelope proteins. The result is a pseudotyped virus particle, also called a pseudovirus. With this method, the foreign viral envelope proteins can be used to alter host tropism or increase or decrease the stability of the virus particles. Pseudotyped particles do not carry the genetic material to produce additional viral envelope proteins, so the phenotypic changes cannot be passed on to progeny viral particles. In some cases, the inability to produce viral envelope proteins renders the pseudovirus replication incompetent. In this way, the properties of dangerous viruses can be studied in a lower risk setting.

Alice S. Huang (simplified Chinese: 黄诗厚; traditional Chinese: 黃詩厚; pinyin: Huáng Shīhòu; Wade–Giles: Huang Shih-hou; is an American biologist specialized in microbiology and virology. She served as President of AAAS during the 2010–2011 term.

<span class="mw-page-title-main">Marburg virus</span> Species of filamentous virus responsible for hemorrhagic fever

Marburg virus (MARV) is a hemorrhagic fever virus of the Filoviridae family of viruses and a member of the species Marburg marburgvirus, genus Marburgvirus. It causes Marburg virus disease in primates, a form of viral hemorrhagic fever. The virus is considered to be extremely dangerous. The World Health Organization (WHO) rates it as a Risk Group 4 Pathogen. In the United States, the National Institute of Allergy and Infectious Diseases ranks it as a Category A Priority Pathogen and the Centers for Disease Control and Prevention lists it as a Category A Bioterrorism Agent. It is also listed as a biological agent for export control by the Australia Group.

<i>Zaire ebolavirus</i> Species of virus affecting humans and animals

Zaire ebolavirus, more commonly known as Ebola virus, is one of six known species within the genus Ebolavirus. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and other mammals, known as Ebola virus disease (EVD). Ebola virus has caused the majority of human deaths from EVD, and was the cause of the 2013–2016 epidemic in western Africa, which resulted in at least 28,646 suspected cases and 11,323 confirmed deaths.

rVSV-ZEBOV vaccine Vaccine against Ebola virus disease

Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV), also known as Ebola Zaire vaccine live and sold under the brand name Ervebo, is an Ebola vaccine for adults that prevents Ebola caused by the Zaire ebolavirus. When used in ring vaccination, rVSV-ZEBOV has shown a high level of protection. Around half the people given the vaccine have mild to moderate adverse effects that include headache, fatigue, and muscle pain.

<span class="mw-page-title-main">Ebola vaccine</span> Vaccine against Ebola

Ebola vaccines are vaccines either approved or in development to prevent Ebola. As of 2022, there are only vaccines against the Zaire ebolavirus. The first vaccine to be approved in the United States was rVSV-ZEBOV in December 2019. It had been used extensively in the Kivu Ebola epidemic under a compassionate use protocol. During the early 21st century, several vaccine candidates displayed efficacy to protect nonhuman primates against lethal infection.

David Mahan Knipe is the Higgins Professor of Microbiology and Molecular Genetics in the Department of Microbiology at the Harvard Medical School in Boston, Massachusetts and co-chief editor of the reference book Fields Virology. He returned to the Chair of the Program in Virology at Harvard Medical School in 2019, having previously held the position from 2004 through 2016 and served as interim Co-Chair of the Microbiology and Immunobiology Department from 2016 through 2018.

Judith Alice Lesnaw is an American virologist, photographer, and inductee of the University of Kentucky's Hall of Fame. She was the first woman hired into Biology, the first woman to be tenured, and the first molecular biologist at the University of Kentucky.

<span class="mw-page-title-main">Negative-strand RNA virus</span> Phylum of viruses

Negative-strand RNA viruses are a group of related viruses that have negative-sense, single-stranded genomes made of ribonucleic acid (RNA). They have genomes that act as complementary strands from which messenger RNA (mRNA) is synthesized by the viral enzyme RNA-dependent RNA polymerase (RdRp). During replication of the viral genome, RdRp synthesizes a positive-sense antigenome that it uses as a template to create genomic negative-sense RNA. Negative-strand RNA viruses also share a number of other characteristics: most contain a viral envelope that surrounds the capsid, which encases the viral genome, −ssRNA virus genomes are usually linear, and it is common for their genome to be segmented.

Jack D. Keene is a James B. Duke Professor of Molecular Genetics and Microbiology at Duke University.

<span class="mw-page-title-main">Andrea Marzi</span> German-American virologist

Andrea Marzi is a German-American virologist. She is chief of the immunobiology and molecular virology unit at the Rocky Mountain Laboratories. Marzi investigates the pathogenesis of filoviruses and vaccine development. She received the Loeffler-Frosch medal in recognition of her research.

<span class="mw-page-title-main">Viral vector vaccine</span> Type of vaccine

A viral vector vaccine is a vaccine that uses a viral vector to deliver genetic material (DNA) that can be transcribed by the recipient's host cells as mRNA coding for a desired protein, or antigen, to elicit an immune response. As of April 2021, six viral vector vaccines, four COVID-19 vaccines and two Ebola vaccines, have been authorized for use in humans.

Endothelial cell tropism or endotheliotropism is a type of tissue tropism or host tropism that characterizes an pathogen's ability to recognize and infect an endothelial cell. Pathogens, such as viruses, can target a specific tissue type or multiple tissue types. Like other cells, the endothelial cell possesses several features that supports a productive viral infection a cell including, cell surface receptors, immune responses, and other virulence factors. Endothelial cells are found in various tissue types such as in the capillaries, veins, and arteries in the human body. As endothelial cells line these blood vessels and critical networks that extend access to various human organ systems, the virus entry into these cells can be detrimental to virus spread across the host system and affect clinical course of disease. Understanding the mechanisms of how viruses attach, enter, and control endothelial functions and host responses inform infectious disease understanding and medical countermeasures.

Jay Clark Brown is an American molecular biologist, microbiologist, virologist, and academic. He is a Professor Emeritus in the Department of microbiology, immunology, and cancer biology at the University of Virginia School of Medicine.

References

  1. 1 2 Carette, Jan E.; Raaben, Matthijs; Wong, Anthony C.; Herbert, Andrew S.; Obernosterer, Gregor; Mulherkar, Nirupama; Kuehne, Ana I.; Kranzusch, Philip J.; Griffin, April M. (24 August 2011). "Ebola virus entry requires the cholesterol transporter Niemann-Pick C1". Nature. 477 (7364): 340–343. Bibcode:2011Natur.477..340C. doi:10.1038/nature10348. ISSN   1476-4687. PMC   3175325 . PMID   21866103.
  2. 1 2 "Scientists find weakness in deadly Ebola virus". Reuters. 24 August 2011. Retrieved 21 February 2019.
  3. 1 2 "Attacking Ebola". Harvard Gazette. 24 August 2011. Retrieved 22 February 2019.
  4. 1 2 Whelan, Sean P. J.; Piccinotti, Silvia (27 July 2016). "Rabies Internalizes into Primary Peripheral Neurons via Clathrin Coated Pits and Requires Fusion at the Cell Body". PLOS Pathogens. 12 (7): e1005753. doi: 10.1371/journal.ppat.1005753 . ISSN   1553-7374. PMC   4963122 . PMID   27463226.
  5. 1 2 3 "Ribosome regulates viral protein synthesis, revealing potential therapeutic target". ScienceDaily. Retrieved 22 February 2019.
  6. 1 2 Whelan, Sean P. J.; Burdeinick-Kerr, Rebeca; Lee, Amy Si-Ying (2 January 2013). "A ribosome-specialized translation initiation pathway is required for cap-dependent translation of vesicular stomatitis virus mRNAs". Proceedings of the National Academy of Sciences. 110 (1): 324–329. doi: 10.1073/pnas.1216454109 . ISSN   0027-8424. PMC   3538191 . PMID   23169626.
  7. ↑ "Whelan named head of molecular microbiology". Washington University School of Medicine in St. Louis. 18 July 2019. Retrieved 11 October 2019.
  8. ↑ "Sean Whelan to be head of the Department of Molecular Microbiology | Office of Neuroscience Research | Washington University in St. Louis". neuroscienceresearch.wustl.edu. Retrieved 11 October 2019.
  9. 1 2 "2020-02-16: NOGLSTSP Recognizes Brownell, Dell, and Whelan as LGBTQ+ Educator, Engineer, and Scientist of the Year for 2020 and Queer Science as Organization of the Year – NOGLSTP" . Retrieved 17 February 2020.
  10. ↑ "Whelan named LGBTQ+ scientist of the year". Washington University School of Medicine in St. Louis. 17 February 2020. Retrieved 2 June 2020.
  11. ↑ "Program in Virology". www.hms.harvard.edu. Retrieved 20 July 2019.
  12. ↑ "Centers of Excellence for Translational Research (CETR) Locations | NIH: National Institute of Allergy and Infectious Diseases". www.niaid.nih.gov. Retrieved 20 July 2019.
  13. ↑ "Whelan named head of molecular microbiology". Washington University School of Medicine in St. Louis. 18 July 2019. Retrieved 19 July 2019.
  14. ↑ Whelan, S. P.; Ball, L. A.; Barr, J. N.; Wertz, G. T. (29 August 1995). "Efficient recovery of infectious vesicular stomatitis virus entirely from cDNA clones". Proceedings of the National Academy of Sciences of the United States of America. 92 (18): 8388–8392. Bibcode:1995PNAS...92.8388W. doi: 10.1073/pnas.92.18.8388 . ISSN   0027-8424. PMC   41162 . PMID   7667300.
  15. ↑ USPatent 5789229,G.W. Wertz, Q. Yu, A. Ball, J.N. Barr, and S.P.J. Whelan,"Gene Therapy Vectors and Vaccines Based on Non-segmented Negative-Stranded RNA Viruses",issued 1998-1-1
  16. ↑ Whitt, Michael A. (2010). "Generation of VSV Pseudotypes Using Recombinant ΔG-VSV for Studies on Virus Entry, Identification of Entry Inhibitors, and Immune Responses to Vaccines". Journal of Virological Methods. 169 (2): 365–374. doi:10.1016/j.jviromet.2010.08.006. ISSN   0166-0934. PMC   2956192 . PMID   20709108.
  17. ↑ Chandran, Kartik; Sullivan, Nancy J.; Felbor, Ute; Whelan, Sean P.; Cunningham, James M. (10 June 2005). "Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection". Science. 308 (5728): 1643–1645. Bibcode:2005Sci...308.1643C. doi:10.1126/science.1110656. ISSN   1095-9203. PMC   4797943 . PMID   15831716.
  18. 1 2 "The Future of Molecular Visualization | Harvard Medical School". hms.harvard.edu. Retrieved 21 February 2019.
  19. ↑ Liang, Bo; Li, Zongli; Jenni, Simon; Rahmeh, Amal A.; Morin, Benjamin M.; Grant, Timothy; Grigorieff, Nikolaus; Harrison, Stephen C.; Whelan, Sean P. J. (16 July 2015). "Structure of the L Protein of Vesicular Stomatitis Virus from Electron Cryomicroscopy". Cell. 162 (2): 314–327. doi:10.1016/j.cell.2015.06.018. ISSN   1097-4172. PMC   4557768 . PMID   26144317.
  20. ↑ "Scientists for Science". www.scientistsforscience.org. Retrieved 23 February 2019.
  21. ↑ Roos, Robert (30 July 2014). "Scientists voice support for research on dangerous pathogens". CIDRAP. Retrieved 21 February 2019.
  22. ↑ "Grant Recipients 2002-2005 | Burroughs Wellcome Fund". www.bwfund.org. Retrieved 17 February 2020.
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