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Jacob Yount, PhD


460 W 12th Ave
Columbus, OH 43210

Phone: (614) 688-1639

Email: yount.37@osu.edu

 

Current OSU Appointment

Assistant Professor, SBS-Microbial Infectn/Immunity

 

Noteworthy Graduate Narrative

Soon after starting at OSU, I recruited two graduate students into my laboratory from the BIomedical Sciences Graduate Program. I have successfully mentored these students toward receiving multiple awards and fellowships. Most notably, my commitment to the success of my students is evidenced by the fact that both of these students have each received two fellowships. I will further describe the unique accomplishments of each student below.

Nicholas Chesarino - Nick was the recipient of the OSU Systems and Integrated Biology 2-year fellowship sponsored by the NIH, and based on a research proposal and panel interview of the student and mentor, as well as a renewal interview for the second year of funding. Nick has also received Trainee Abstract Awards for attendance at the American Association of Immunologists annual meeting in both 2014 and 2015. Nick was chosen and gave an oral presentation at this meeting in 2015. Nick also received the N. Paul Hudson Award for Research Excellence at the 2014 Ohio Branch American Society for Microbiology Annual Meeting for his poster presentation as chosen by faculty judges. Nick was also only one of a handful of students chosen for a Travel Grant to attend the 2015 Innate Immunity and MIcrobial Pathogenesis Keystone Meeting. Nick has also authored 6 peer-reviewed articles to date on his work in my laboratory. Based on these accomplishments, Nick was recently awarded the OSU Presidential Fellowship to fund his final year of graduate research. He was also recently nominated by me and his graduate program for the Harold M. Weintraub Graduate Student Award given by the Fred Hutchinson Cancer Center, and we are awaiting the results of this competition.

Temet McMichael - In 2014, Temet received an honorabe mention from the Ford Foundation Predoctoral Fellowship Competition, and was awarded a 3-year American Society for Microbiology (ASM) Watkins Predoctoral Fellowship. In 2015, Temet was awarded the 3-year Howard Hughes Medical Institute Gilliam Fellowship, and declined the remaining funding from his ASM fellowship, though was invited to remain an ASM Fellow. Temet has received travel awards to attend the 2014 American Association of Immunologists Annual Meeting and the 2014 Society for the Advancement of Chicanos and Native Americans Annual Conference. Temet was chosen to give an oral presentation at the Ohio Branch ASM Annual Meeting in 2014, and also presented at the OSUMC Trainee Research Day where he was awarded a Travel Award for an "exceptional" research poster presentation as determined by faculty judges. Temet has been an author on 5 peer-reviewed articles while in my laboratory.

I have also mentored one OSU medical student in my laboratory, William James Melvin. James received a 2014 Roessler Medical Student Research Scholarship to support his research in my laboratory during the summer of 2014. James presented in our departmental work in progress seminar, received a Travel Award at the OSUMC Trainee Research Day for his "exceptional" poster presentation in 2015, and was co-first author on a publication from my laboratory.

Advising Narrative

Victoria Soewarna was the first undergraduate recruited to my laboratory. VIctoria has received three research scholarships, a 2014 SOLAR Undergraduate Research Scholarship, a 2015 Summer Undergraduate Research Scholarship, and a 2015-2016 OSU Arts and Sciences Honors Committee Scholarship for Research.

I also mentor Rachel Doering who performed summer research for credit during the summer of 2015, and continues to work in the lab during her senior year. Matthew Davis , a student in the Biomedical Sciences undergraduate degree program, has also very recently joined the laboratory and performs research for credit as required of his program.

Biographical

I have had a rare set of multidisciplinary training experiences in viral immunology, lipid biochemistry, and chemical biology. As an undergraduate I sought out research experiences at the University of Pittsburgh. I was awarded two research fellowships, including one funded by the Howard Hughes Medicine Institute, and worked in two applied organic chemistry labs. These experiences made me appreciate the value of chemical tools for answering biological questions early on in my research career. This was followed by my graduate training in viral immunology at the Mt. Sinai School of Medicine where I was co-mentored by Drs. Thomas Moran and Carolina Lopez in one of the world's preeminent departments for the study of viral immunology. Here I was thoroughly fascinated by the different abilities of certain related virus strains to either strongly activate immune cells or to go virtually undetected. I went on to determine that “mistakes” of virus replication known as defective interfering genomes that are more prevalent in certain virus stocks than others have a uniquely potent ability to activate specific virus-sensing proteins because of their unusual RNA structure. My work resulted in nine publications, including three first-author research articles, and a patent application, and was chosen for an oral presentation at the International Congress of Immunology in Rio de Janeiro, Brazil. My findings have since been validated by studies from the laboratories of Drs. Adolfo Garcia-Sastre and Peter Palese at Mt. Sinai, and these defective interfering genomes are being actively pursued as a novel vaccine adjuvant in the laboratory of Dr. Carolina Lopez, who has since moved her laboratory to the University of Pennsylvania.&emsp

&emspFor my postdoctoral work, I chose the chemical biology laboratory of Dr. Howard Hang at the Rockefeller University because I saw the immense potential of the chemical tools being developed there for the study of protein lipidation, and recognized the importance of these post-translational modifications in nearly all fields of biomedical research, including innate and adaptive immunity. I chose to study protein palmitoylation because unlike other lipid modifications, palmitoylation does not occur at a predictable motif and we therefore had much to gain in finding new palmitoylated proteins. I developed methods for global proteomic analysis of palmitoylated proteins by mass spectrometry using a chemical reporter strategy, which, among many other proteins, identified Interferon-Induced Transmembrane Protein 3 (IFITM3) as a potentially palmitoylated protein. Despite a lack of prior studies on IFITM3 at this time, its reported induction by the antiviral cytokine interferon piqued my curiosity, and I went on to demonstrate that palmitoylation of IFITM3 affects its membrane affinity and homotypic clustering in cellular membranes, and that IFITM3 possesses a palmitoylation-dependent ability to inhibit influenza virus. During the final years of my postdoctoral fellowship, I was co-mentored by National Academy of Sciences member, Dr. Charles Rice, and learned additional techniques for studying viruses and antiviral immunity. During my time at the Rockefeller University, I was awarded a three-year immunology fellowship from the Cancer Research Institute, a Career Development Award from the Rockefeller University Postdoctoral Association, and an NIH K99/R00 Pathway to Independence Award that received a perfect score of 10. My postdoctoral work resulted in eight publications, 6 of which were first-author, and a patent application, and I was chosen to orally present this work at the International Congress of Immunology in Kobe, Japan. Two of my first-author research articles were published in top tier chemistry journals, Nature Chemical Biology and the Journal of the American Chemical Society, and my work received a “Must Read” citation from Faculty of 1000 Biology.

&emsp I joined the Ohio State University at the rank of Assistant Professor, without tenure, in October of 2012, and quickly established my independent laboratory. The underlying tenet of my research is that through understanding the post-translational mechanisms controlling innate immunity, we will uncover strategies to exploit the immune system for the benefit human health. Post-translational modifications modulate the activity of proteins, often turning immune effector proteins “on” or “off.” Furthermore, since these are generally enzymatic additions, they can presumably be inhibited with small molecules. We are making significant progress toward understanding the IFITM family of antiviral proteins in terms of their mechanism of action and the post-translational modifications that govern their localization, activity, and turnover. In my laboratory’s first three years, we published seven primary research articles in the Journal of Virology, the Journal of Biological Chemistry, BMC Biology, Virology, Viruses, and PLOS Pathogens. As a result of our publications, I was invited to review the literature on IFITM3 post-translational modifications for Future Microbiology. Additionally, I was recently invited to present my laboratory’s work at the 2015 Innate Immunity and Determinants of Microbial Pathogenesis Keystone Meeting Workshop on Systems Biology. The past two years, I have also received Early Career Faculty Travel Awards from the American Association of Immunologists for attendance at their annual meetings at which research abstracts from my laboratory were chosen for oral presentation both years. I was also recently invited to present one of the faculty talks at this year’s Midwest Microbial Pathogenesis conference to be held in Indianapolis, IN. Student presenters from my laboratory have also been chosen the past two years to speak at the Ohio Branch American Society for Microbiology (ASM) Annual Meeting. I have also had funding successes in addition to my NIH R00 award; I was awarded a two-year grant from the OSU PHPID program for studying post-translational modifications of Toll-like receptors that control microbe-mediated inflammation, a pilot grant from ARNO Pharmaceuticals to test one of their clinically relevant compounds for activity against influenza virus, and an NIH Short Term High Priority R56 grant for some of our mechanistic studies into the abilities of IFITM3 to shape membranes as mentioned below. In my laboratory, we continue to work toward a deeper understanding of the mechanisms controlling the immune system.

Academic Advising

2013 - present , The Ohio State University.
2013 Temet McMichael, The Ohio State University. Graduated 0.
2013 Nicholas Chesarino, The Ohio State University. Graduated 0.
2014 Matthew Sermersheim, The Ohio State University. Graduated 0.
2014 Victoria Soewarna, The Ohio State University. Graduated 0.
2015 Matthew Davis, The Ohio State University. Graduated 0.
2013 - 2014 William James, The Ohio State University. Graduated 0.
2015 - 2016 Rachel Doering, The Ohio State University. Graduated 2016.
 

Degrees

2002 B.S., Grove City College

 

Editorial Activities

2012 Future Virology
2013 Journal of Molecular Biology
2013 PLOS One
2014 Journal of Virology
2014 Scientific Reports
2014 Molecular and Cellular Biology
2014 Infection and Immunity
2015 PLOS Pathogens
2015 Journal of the American Chemical Society
2015 BMC Medical Genetics
2015 Journal of Clinical Investigation
2015 EMBO Reports
2015 Cell Reports
2016 - present PLOS Pathogens
2016 - present Critical Reviews in Microbiology
2016 BMC Research Notes
 

Honors

2014 - present American Association of Immunologists Early Career Travel Grant. American Association of Immunologists.
2015 - present OSU Nominee for Pew Scholars Program. The Ohio State University.
2015 - present American Association of Immunologists Early Career Travel Grant. American Association of Immunologists.
2015 - present OSU Nominee for Mallinckrodt Grants Program. The Ohio State University.
2015 - present Induction into Sigma Xi Scientific Honorary. Sigma Xi.
2016 - present American Association of Immunologists Early Career Travel Grant. American Association of Immunologists.
 

Journal Articles

Yount,Jacob,S; Moran,Thomas,M; Lopez,Carolina,B. "Enhancement of dendritic cell maturation by viral defective interfering particles." JOURNAL OF IMMUNOLOGY. Vol. 176, (April 2006.): S105-S105.

Lopez,C,B; Yount,J,S; Moran,T,M. "Toll-like receptor-independent triggering of dendritic cell maturation by viruses." JOURNAL OF VIROLOGY. Vol. 80, no. 7. (April 2006.): 3128-3134.

Lopez,C,B; Yount,J,S; Hermesh,T; Moran,T,M. "Sendai virus infection induces efficient adaptive immunity independently of type I Interferons." JOURNAL OF VIROLOGY. Vol. 80, no. 9. (May 2006.): 4538-4545.

Yount,Jacob,S; Kraus,Thomas,A; Horvath,Curt,M; Moran,Thomas,M; Lopez,Carolina,B. "A novel role for viral-defective interfering particles in enhancing dendritic cell maturation." JOURNAL OF IMMUNOLOGY. Vol. 177, no. 7. (October 2006.): 4503-4513.

Yount,Jacob,S; Moran,Thomas,M; Lopez,Carolina,B. "Cytokine-independent upregulation of MDA5 in viral infection." JOURNAL OF VIROLOGY. Vol. 81, no. 13. (July 2007.): 7316-7319.

Yount,Jacob,S; Gitlin,Leonid; Moran,Thomas,M; Lopez,Carolina,B. "MDA5 participates in the detection of paramyxovirus infection and is essential for the early activation of dendritic cells in response to Sendai virus defective interfering particles." JOURNAL OF IMMUNOLOGY. Vol. 180, no. 7. (April 2008.): 4910-4918.

Friedman,Constantin,S; O'Donnell,Marie,Anne; Legarda-Addison,Diana; Ng,Aylwin; Cardenas,Washington,B; Yount,Jacob,S; Moran,Thomas,M; Basler,Christopher,F; Komuro,Akihiko; Horvath,Curt,M; Xavier,Ramnik; Ting,Adrian,T. "The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response." EMBO REPORTS. Vol. 9, no. 9. (September 2008.): 930-936.

Charron,Guillaume; Zhang,Mingzi,M; Yount,Jacob,S; Wilson,John; Raghavan,Anuradha,S; Shamir,Eliah; Hang,Howard,C. "Robust Fluorescent Detection of Protein Fatty-Acylation with Chemical Reporters." JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. Vol. 131, no. 13. (April 2009.): 4967-4975.

Cotter,Christopher,R; Nguyen,Marie,L; Yount,Jacob,S; Lopez,Carolina,B; Blaho,John,A; Moran,Thomas,M. "The Virion Host Shut-Off (vhs) Protein Blocks a TLR-Independent Pathway of Herpes Simplex Virus Type 1 Recognition in Human and Mouse Dendritic Cells." PLOS ONE. Vol. 5, no. 2. (February 2010.): e8684-.

Yount,Jacob,S; Moltedo,Bruno; Yang,Yu-Ying; Charron,Guillaume; Moran,Thomas,M; Lopez,Carolina,B; Hang,Howard,C. "Palmitoylome profiling reveals S-palmitoylation-dependent antiviral activity of IFITM3." NATURE CHEMICAL BIOLOGY. Vol. 6, no. 8. (August 2010.): 610-614.

Yount,Jacob,S; Tsou,Lun,K; Dossa,Paul,D; Kullas,Amy,L; van der Velden,Adrianus,WM; Hang,Howard,C. "Visible Fluorescence Detection of Type III Protein Secretion from Bacterial Pathogens." JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. Vol. 132, no. 24. (June 2010.): 8244-?.

Charron,Guillaume; Tsou,Lun,K; Maguire,William; Yount,Jacob,S; Hang,Howard,C. "Alkynyl-farnesol reporters for detection of protein S-prenylation in cells." MOLECULAR BIOSYSTEMS. Vol. 7, no. 1. (January 2011.): 67-73.

Moltedo,Bruno; Li,Wenjing; Yount,Jacob,S; Moran,Thomas,M. "Unique Type I Interferon Responses Determine the Functional Fate of Migratory Lung Dendritic Cells during Influenza Virus Infection." PLOS PATHOGENS. Vol. 7, no. 11. (November 2011.): e1002345-.

Cotter,Christopher,R; Kim,Won-Keun; Nguyen,Marie,L; Yount,Jacob,S; Lopez,Carolina,B; Blaho,John,A; Moran,Thomas,M. "The Virion Host Shutoff Protein of Herpes Simplex Virus 1 Blocks the Replication-Independent Activation of NF-kappa B in Dendritic Cells in the Absence of Type I Interferon Signaling." JOURNAL OF VIROLOGY. Vol. 85, no. 23. (December 2011.): 12662-12672.

Yount,Jacob,S; Charron,Guillaume; Hang,Howard,C. "Bioorthogonal proteomics of 15-hexadecynyloxyacetic acid chemical reporter reveals preferential targeting of fatty acid modified proteins and biosynthetic enzymes." BIOORGANIC & MEDICINAL CHEMISTRY. Vol. 20, no. 2. (January 2012.): 650-654.

Yount,Jacob,S; Karssemeijer,Roos,A; Hang,Howard,C. "S-Palmitoylation and Ubiquitination Differentially Regulate Interferon-induced Transmembrane Protein 3 (IFITM3)-mediated Resistance to Influenza Virus." JOURNAL OF BIOLOGICAL CHEMISTRY. Vol. 287, no. 23. (June 2012.): 19631-19641.

Yount,Jacob,S; Zhang,Mingzi,M; Hang,Howard,C. "Emerging roles for protein S-palmitoylation in immunity from chemical proteomics." CURRENT OPINION IN CHEMICAL BIOLOGY. Vol. 17, no. 1. (February 2013.): 27-33.

Hach,Jocelyn,C; McMichael,Temet; Chesarino,Nicholas,M; Yount,Jacob,S. "Palmitoylation on Conserved and Nonconserved Cysteines of Murine IFITM1 Regulates Its Stability and Anti-Influenza A Virus Activity." JOURNAL OF VIROLOGY. Vol. 87, no. 17. (September 2013.): 9923-9927.

Gelais,Corine,St; de Silva,Suresh; Hach,Jocelyn,C; White,Tommy,E; Diaz-Griffero,Felipe; Yount,Jacob,S; Wu,Li. "Identification of Cellular Proteins Interacting with the Retroviral Restriction Factor SAMHD1." JOURNAL OF VIROLOGY. Vol. 88, no. 10. (May 2014.): 5834-5844.

Chesarino,Nicholas,M; McMichael,Temet,M; Hach,Jocelyn,C; Yount,Jacob,S. "Phosphorylation of the Antiviral Protein Interferon-inducible Transmembrane Protein 3 ( IFITM3) Dually Regulates Its Endocytosis and Ubiquitination." JOURNAL OF BIOLOGICAL CHEMISTRY. Vol. 289, no. 17. (April 2014.): 11986-11992.

Chesarino,Nicholas,M; McMichael,Temet,M; Yount,Jacob,S. "Regulation of the trafficking and antiviral activity of IFITM3 by post-translational modifications." FUTURE MICROBIOLOGY. Vol. 9, no. 10. (January 2014.): 1151-1163.

Chesarino,Nicholas,M; Hach,Jocelyn,C; Chen,James,L; Zaro,Balyn,W; Rajaram,Murugesan,VS; Turner,Joanne; Schlesinger,Larry,S; Pratt,Matthew,R; Hang,Howard,C; Yount,Jacob,S. "Chemoproteomics reveals Toll-like receptor fatty acylation." BMC BIOLOGY. Vol. 12, (November 2014.): 91-.

Melvin,William,J; McMichael,Temet,M; Chesarino,Nicholas,M; Hach,Jocelyn,C; Yount,Jacob,S. "IFITMs from Mycobacteria Confer Resistance to Influenza Virus When Expressed in Human Cells." VIRUSES-BASEL. Vol. 7, no. 6. (June 2015.): 3035-3052.

Wang F, St. Gelais C, de Silva S, Zhang H, Geng Y, Shepard C, Kim B, Yount JS, Wu L. "Phosphorylation of mouse SAMHD1 regulates its restriction of human immunodeficiency virus type 1 infection, but not murine leukemia virus infection." Virology. Vol. 487, (November 2015.): 273-284.

Chesarino,Nicholas,M; McMichael,Temet,M; Yount,Jacob,S. "E3 Ubiquitin Ligase NEDD4 Promotes Influenza Virus Infection by Decreasing Levels of the Antiviral Protein IFITM3." PLOS PATHOGENS. Vol. 11, no. 8. (August 2015.): e1005095-.

Wang,Feifei; Gelais,Corine,St; de Silva,Suresh; Zhang,Hong; Geng,Yu; Shepard,Caitlin; Kim,Baek; Yount,Jacob,S; Wu,Li. "Phosphorylation of mouse SAMHD1 regulates its restriction of human immunodeficiency virus type 1 infection, but not murine leukemia virus infection." VIROLOGY. Vol. 487, (January 2016.): 273-284.

Tsou,Lun,K; Lara-Tejero,Maria; RoseFigura,Jordan; Zhang,Zhenrun,J; Wang,Yen-Chih; Yount,Jacob,S; Lefebre,Matthew; Dossa,Paul,D; Kato,Junya; Guan,Fulan; Lam,Wing; Cheng,Yung-Chi; Galan,Jorge,E; Hang,Howard,C. "Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates." JOURNAL OF THE AMERICAN CHEMICAL SOCIETY. Vol. 138, no. 7. (February 2016.): 2209-2218.

 

Presentations

"Tyrosine phosphorylation of IFITM3 blocks an endocytic motif necessary for its complete influenza virus restrictio." Presented at American Association of Immunologists Anual Meeting 2014, . (April 2014)

"Chemoproteomics reveals Toll-like receptor fatty acylation." Presented at Innate Immunity and Determinants of Microbial Pathogenesis Keystone Meeting, . (April 2015)

"Identification of a novel cellular target for broadly inhibiting influenza virus infection." Presented at Midwest Microbial Pathogenesis Conference 2015, . (August 2015)

"IFITM3 and a new cellular target for broadly inhibiting influenza virus infections." Presented at Oklahoma Center for Respiratory and Infectious Diseases (OCRID) of Oklahoma State University, . (February 2016)

"Identification of a novel cellular target for broadly inhibiting influenza virus infection." Presented at University of Toledo Medical Microbiology and Immunology, . (January 2016)

"An amphipathicity-based mechanism for antiviral activity of IFITM3." Presented at Gordon Research Conference: Viruses and Cells, Lucca, IT|ITA. (May 2017)

"How does IFITM3 broadly inhibit virus infections?." Presented at Icahn School of Medicine at Mount Sinai, Department of Microbiology, New York, NY, . (March 2017)

"How does IFITM3 limit influenza virus infections?." Presented at West Virginia University, College of Medicine, Immunology and Microbial Pathogenesis Seminar Series, Morgantown. (April 2017)

"An amphipathicity-based mechanism for antiviral activity of IFITM3." Presented at Medical College of Wisconsin, Department of Microbiology and Molecular Genetics, Milwaukee. (October 2017)

 

Professional Activities

present American Heart Association Ad Hoc Reviewer (Microbiology 2).
present American Heart Association Ad Hoc Reviewer (Microbiology 2).
present NIH Study Section Ad Hoc Reviewer (Virology B).
present American Heart Association Ad Hoc Reviewer (Microbiology 2).
 

Unpublished Works

Tsou LK, Lara-Tejero M, Zhang Z, Wang Y-C, Yount JS, Lefefre M, Dossa P, Kata J, Guan F, Lam W, Cheng Y-C, Galan J, and Hang HC. Flavonoids from medicinal plants inhibit bacterial virulence by inactivating type III secretion protein effectors. November 2015.

Antonucci J, St. Gelais C, de Silva S, Yount JS, Tang C, Ji X, Xiong Y, Kim B, and Wu L. Comments on: Ryoo J, et al. The ribonuclease activity of SAMHD1 is required for HIV-1 restriction. Nat Med. 2014; 20(8):936-41. September 2015.

Jacob S. Yount. Genetic Determinants of Host VIral Susceptibility (Editorial Board Invitation for 2017 Issue of Annual Review of Genetics). January 0.

Percher A, Ramakrishnan S, Yuan X, Thinon E, Yount JS*, and Hang HC* (*Co-corresponding authors). Acyl-PEG exchange reveals site-specific and quantitative levels of protein S-fatty acylation. May 2015.