Sigal, Luis J.

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Luis J Sigal

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With some risk-taking and luck: A veterinarian's adventures in viral immunology.

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Thomas Jefferson UniversityJefferson Digital CommonsDepartment of Microbiology and ImmunologyFaculty Papers Department of Microbiology and Immunology7-1-2018With some risk-taking and luck: A veterinarian'sadventures in viral immunology.Luis J. SigalThomas Jefferson University, luis.sigal@jefferson.eduLet us know how access to this document benefits youFollow this and additional works at: https://jdc.jefferson.edu/mifpPart of the Animal Sciences Commons, and the Medical Immunology CommonsThis Article is brought to you for free and open access by the Jefferson Digital Commons. The Jefferson Digital Commons is a service of ThomasJefferson University's Center for Teaching and Learning (CTL). The Commons is a showcase for Jefferson books and journals, peer-reviewed scholarlypublications, unique historical collections from the University archives, and teaching tools. The Jefferson Digital Commons allows researchers andinterested readers anywhere in the world to learn about and keep up to date with Jefferson scholarship. This article has been accepted for inclusion inDepartment of Microbiology and Immunology Faculty Papers by an authorized administrator of the Jefferson Digital Commons. For moreinformation, please contact: JeffersonDigitalCommons@jefferson.edu.Recommended CitationSigal, Luis J., "With some risk-taking and luck: A veterinarian's adventures in viral immunology."(2018). Department of Microbiology and Immunology Faculty Papers. Paper 95.https://jdc.jefferson.edu/mifp/95RESEARCH MATTERSWith some risk-taking and luck: Aveterinarian’s adventures in viral immunologyLuis J. Sigal*Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania,United States of America* Luis.Sigal@jefferson.eduLike many other kids, I had already decided my future at the mature age of 5. Because I likedanimals, I was going to be a veterinarian. Unlike most kids, I did not change my mind as Igrew up, and 19 years later, I graduated with a veterinary degree from the University of BuenosAires, Argentina. I opened a small practice in a semirural town near Buenos Aires. However,my practice was not as exciting as my childhood dreams. My days were filled with giving vac-cine shots, rehydrating dogs suffering from parvovirus or distemper (most of which died), andperforming the spine-chilling job of removing fly maggots from open wounds in the hot sum-mer months. About 4 years into the profession, I decided that being a veterinarian bored meand that what really interested me was not to give vaccine shots but to find out how pathogensproduced diseases and how vaccines prevented them. I learned that my veterinary school hadjust appointed a new professor of immunology, Marta Braun, who was starting a researchprogram in viral immunology and vaccines against foot-and-mouth-disease virus in cattle.I knocked on Marta’s office door and told her that I was interested in doing research. Eventhough I had no research experience, I was lucky that she liked me and offered me a positionas a teaching and research assistant. I took the risk, sold my practice, and from then on, myprofessional life centered on research in viral immunology. A couple of years later, Argentinareached the staggering annual inflation rate of approximately 3,000% (yes, 3,000!). Because theeconomic situation was so dire, my wife Norma and I decided to try finding a place abroadwhere I could do a PhD, hoping that, in the interim, the situation in Argentina would improve.Friends of Marta at the University of Nebraska recommended me to Dwane Wylie, an associ-ate professor of immunology. For reasons I still do not know, Dwane decided to sponsor me toenter the PhD program and hired me as a research assistant without ever meeting me. I movedto Nebraska with Norma in July 1990 without having ever been there and started my PhD inSeptember. Dwane gave me incredible freedom to pursue my interests. A great new discoveryat the time was that CD8 T cells recognized viral antigen as peptides bound to a groove insidemajor histocompatibility complex (MHC) class I molecules. I found this fascinating anddecided to focus my dissertation on understanding how influenza virus peptides interactedwith MHC I, which was only obliquely related to Dwane’s own current interests. This broughtme right into the field of antigen presentation.As I was finishing my PhD in 1994, I wrote many letters (snail mail at the time) requestingpostdoctoral positions to the big shots in antigen presentation. I was lucky that one of them,Kenneth Rock, then at the Dana Farber Cancer Institute and Harvard Medical School,answered and invited me for an interview. Ken liked me and offered me a position on the spot.A main interest in Ken’s lab was cross-presentation, a process whereby dendritic cells andmacrophages take up exogenous antigens and present their peptides with their own MHCPLOS Pathogens | https://doi.org/10.1371/journal.ppat.1007000 July 5, 2018 1 / 3a1111111111a1111111111a1111111111a1111111111a1111111111OPENACCESSCitation: Sigal LJ (2018) With some risk-takingand luck: A veterinarian’s adventures in viralimmunology. PLoS Pathog 14(7): e1007000.https://doi.org/10.1371/journal.ppat.1007000Editor: Glenn F Rall, The Fox Chase Cancer Center,UNITED STATESPublished: July 5, 2018Copyright: © 2018 Luis J. Sigal. This is an openaccess article distributed under the terms of theCreative Commons Attribution License, whichpermits unrestricted use, distribution, andreproduction in any medium, provided the originalauthor and source are credited.Funding: The authors received no specific fundingfor this study.Competing interests: The authors have declaredthat no competing interests exist.class I molecules. At the time, however, it was unknown whether cross-presentation was physi-ologically important or just an epiphenomenon. Indeed, we didn’t even know how CD8 T-cellresponses to viruses were initiated. Using bone marrow chimeras and the poxvirus vacciniavirus (VACV, the smallpox vaccine), we showed that only cells of hematopoietic origin caninitiate antiviral CD8 T-cell responses (we later extended this to other viruses), and by collabo-rating with Raul Andino, an Argentinean virologist specialized in poliovirus, we used micetransgenic for the human poliovirus receptor and Raul’s recombinant polioviruses to showthat when hematopoietic cells cannot be infected, they use cross-presentation to take up viralantigens from other infected cells, thereby initiating the antiviral CD8 T-cell response.My postdoctoral work with Ken made a splash and opened the door to establish my ownlab at Fox Chase Cancer Center in Philadelphia as an assistant professor. I initially focusedon solving some outstanding issues in cross-presentation using VACV, for which I rapidlyobtained NIH funding. Yet the project was too much into cell biology, which was not whatmy research passions were. About 2 years after establishing my lab, at a small symposium inMadrid, Spain, I heard presentations by Antonio Alcami and Guna Karupiah on a poxvirusof the mouse known as Ectromelia virus (ECTV). This virus causes mousepox, a disease sim-ilar to human smallpox in some strains of mice but not others and, similar to smallpox, canImage 1. Luis J. Sigal.https://doi.org/10.1371/journal.ppat.1007000.g001PLOS Pathogens | https://doi.org/10.1371/journal.ppat.1007000 July 5, 2018 2 / 3be prevented by immunization with VACV. I immediately became hooked because ECTVoffered a tractable model to study the genetic control of viral disease and to understand howa well-established vaccine protects a natural host. I made the risky move to start a new proj-ect in an area in which I had no experience, but I was lucky that the move paid off. Within afew years, I established a strong and well-funded research program using ECTV to under-stand fundamental problems in viral immunology. Using ECTV, my research team, now atThomas Jefferson University in Philadelphia, has studied many different aspects of genetic,age-related, and vaccine-induced resistance to viral diseases, including the role of variousmechanisms of host innate and adaptive immunity, as well as slick immune evasion counter-measures by the virus. So far, my scientific career has been an exhilarating adventure that Ibelieve made important contributions to our understanding of the pathogenesis and immu-nology of viral infection, the very same interests that brought me into science when I was ayoung but bored veterinarian.PLOS Pathogens | https://doi.org/10.1371/journal.ppat.1007000 July 5, 2018 3 / 3

With some risk-taking and luck: A veterinarian\u27s adventures in viral immunology.

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With some risk-taking and luck: A veterinarian\u27s adventures in viral immunology.

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