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Program Director/Principal Investigator (Last, First, Middle):
Crotty, Shane
BIOGRAPHICAL SKETCH
Provide the following information for the key personnel and other significant contributors.
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NAME
POSITION TITLE
Crotty, Shane, PhD
Associate Professor, Division of Vaccine Discovery
eRA COMMONS USER NAME
SCROTTY
EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)
INSTITUTION AND LOCATION
DEGREE
(if applicable)
YEAR(s)
Massachusetts Institute of Technology (MIT)
Massachusetts Institute of Technology (MIT)
University of California, San Francisco (UCSF)
Emory University School of Medicine,Atlanta, GA
B.S.
B.S.
PhD
Postdoc
1996
1996
2001
2001-2003
FIELD OF STUDY
Biology
Writing
Molecular Biology
Immunology
A. Personal Statement:
Shane Crotty, Ph.D., is an Associate Professor with tenure at the La Jolla Institute for Allergy and Immunology
(LIAI), and is an adjunct Associate Professor in the UCSD Dept. of Medicine. His research focus is on
understanding the immunobiology underlying vaccine function, with particular interest in the roles of these
mechanisms in human viral vaccines and protection from infectious diseases. At University of California, San
Francisco he discovered
a mechanism of action of the antiviral drug ribavirin (Nat. Med. 2000, PNAS 2001), widely used to treat chronic
hepatitis C infections. After working on an AIDS vaccine for several years (Nature 1999, J. Virology 1999, J.
Virology 2001), Dr. Crotty came to the decision that we knew insufficient immunology for rational vaccine
design. His focus since that point has been on taking the steps necessary to build the fundamental
immunology knowledge needed for future rational vaccine design. Dr. Crotty completed postdoctoral work at
the Emory University Vaccine Center with Dr. Rafi Ahmed, studying aspects of the generation and
maintenance of immune memory after viral infections. Since 2003, his laboratory at LIAI has focused on
understanding mechanisms of immunological memory (Nature 2003, J. Exp Med. 2006, J. Immunology
2007), the immunological basis for the development of protective neutralizing antibodies to the smallpox
vaccine (J. Virology 2005, 2008, 2009, and 2009. Immunity 2008, Vaccine 2009), the interactions of B cells
and CD4 T cells (Immunity 2008, Science 2009, Immunity 2011), and the development of follicular helper
CD4 T cells (Science 2009, Immunity 2011, Annual Review of Immunology 2011).
B.Positions and honors:
1995-1996
Research Technician, Massachusetts Institute of Technology (MIT) Biology Department,
Laboratory of Prof. Leonard Guarente.
2001-2003
Postdoctoral Fellow, Emory Vaccine Center, and Dept. of Microbiology and Immunology.
Laboratory of Rafi Ahmed. Emory University School of Medicine.
2003-2009
Assistant Member, La Jolla Institute of Allergy and Immunology (LIAI). La Jolla, CA
2004-2010
Adjunct Assistant Professor, Dept. of Medicine. University of California, San Diego, CA
2010-present Adjunct Associate Professor, Dept. of Medicine. University of California, San Diego, CA
2009-present Associate Member with tenure, La Jolla Institute of Allergy and Immunology (LIAI), La
Jolla, CA
Honors
1991
1995
1996
1996-2001
2002-2003
2004-2008
2005-2009
2007
2009
2009
National Science Foundation (NSF) Young Scholar
Congressional Goldwater National Scholar for Excellence in Science and Mathematics
Massachusetts Institute of Technology (MIT) Holt Prize for Excellence in Scholarship
Howard Hughes Medical Institute Predoctoral Fellow
Cancer Research Institute Postdoctoral Fellow
Cancer Research Institute Young Investigator Award
Pew Scholar in the Biomedical Sciences
AAI Pfizer Showell Junior Faculty Award
American Society for Virology Annual Conf. "State-of-the-Art" Invited Speaker
Cold Spring Harbor Symposium on Harnessing Immunity. Invited Speaker
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Program Director/Principal Investigator (Last, First, Middle):
2010
2010
2010
2010
2010
2010
2010
2010
2011
2012
2012
2010-2014
2012
Crotty, Shane
Keystone Symposium on Viral Immunology. Plenary session Invited Speaker
NIH Vaccine Research Institute (VRC). Invited Speaker
American Association of Immunologists (AAI). Major Symposium, Invited Speaker
MASIR (Measurement of Ag-specific Immune Responses) Conference. Invited Speaker
2010 FASEB "Biology of the Immune System" Conference, Invited Speaker
Chiba University G-COE Symposium, Invited Speaker
Keystone/Gates Symposium on Immunological Mechanisms of Vaccines, Plenary session
Invited Speaker
Annual Meeting of the Immunology Group of Victoria, Australia. Keynote speaker.
40th Japanese Society of Immunologists (JSI) Annual Conference. Invited speaker.
14th International Conference on Lymphocyte Activation and Immune Regulation. Invited
speaker.
Keystone Viral Immunity / HIV Vaccines Conferences Joint Plenary speaker.
IHD NIH Study Section Permanent Member appointment
American Association of Immunologists (AAI)-BD Biosciences Investigator Award
(For outstanding, early-career research contributions to the field of Immunology)
C. Publications (limited to 15)
1. Luis J. Sigal, Shane Crotty, Raul Andino, Kenneth Rock. “Cytotoxic T-cell immunity to virus-infected
non-haematopoietic cells requires presentation of exogenous antigen.” Nature. 1999 Mar 4;398(6722)
77-80. PMID:10078533
2. Shane Crotty, David Maag, Jamie J. Arnold, Weidong Zhong, Johnson Y.N. Lau, Zhi Hong, Raul
Andino, and Craig E. Cameron. “The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus
mutagen.” Nature Medicine. 2000 Dec;6(12) 1375-1379. PMID:11100123
3. Shane Crotty, Chris Miller, Barbara Lohman, Martha R. Neagu, Lara Compton, Ding Lu, Fabien Lu,
Linda Fritts, Jeffrey D. Lifson, and Raul Andino. "Protection against SIV vaginal challenge using Sabin
poliovirus vectors." J. Virology. 2001 Aug;75:7435-7452. PMID: PMCID:114979
4. Shane Crotty, Ellen Kersh, Jennifer Cannons, Pamela Schwartzberg, and Rafi Ahmed. “SAP is required
for generating long-term humoral immunity.” Nature. 2003 Jan 16;421(6920):282-287. PMID:12529646
5. Shane Crotty, Phil Felgner, Huw Davies, John Glidewell, Luis Villarreal, and Rafi Ahmed. “Long term B
cell memory in humans after smallpox vaccination.” J. Immunology. 2003 171:4969-4973.
6. Mette A. Ejrnaes, Christophe M. Filippi, M. M. Martinic, Eleanor M. Ling, Lisa M. Togher, Shane Crotty,
and Matthias G. von Herrath. “Resolution of a chronic viral infection following IL-10 receptor blockade.”
J. Experimental Medicine. 2006 Oct 30;203:2461-72. PMCID: PMC2118120.
7. Mohammed Rafii-El-idrissi Benhnia, Megan M. McCausland, Hua-Poo Su, Kavita Singh, Julia
Hoffmann, D. Huw Davies, Philip L. Felgner, Steven Head, Alessandro Sette, David N. Garboczi,
and Shane Crotty*. “Redundancy and plasticity of neutralizing antibody responses are cornerstone
attributes of the human immune response to the smallpox vaccine.” J. Virology. 2008 82:3751-3768.
PMCID: PMC2268460. *Correponding author.
8. Alessandro Sette, Magdalini Moutaftsi, Juan Moyron-Quiroz,Megan M. McCausland, D. Huw Davies, ,
Robert Johnston, Rafii Mohammed Benhnai, Julia Hoffman, Hua-Poo Su, Kavita Singh, David N.
Garboczi, Steven Head, Howard Grey, Philip L. Felgner, and Shane Crotty*. “Selective CD4+ T cell
help for antibody responses to a large viral pathogen: deterministic linkage of specificities.” Immunity.
2008 Jun;28(6):477-58. PMCID: PMC2504733. *Corresponding author
9. Robert J. Johnston, Amanda C. Poholek, Daniel DiToro, Isharat Yusuf, Danelle Eto, Burton Barnett,
Alexander L. Dent, Joe Craft and Shane Crotty*. “Bcl6 and Blimp-1 are reciprocal and antagonistic
regulators of T follicular helper cell differentiation.” Science. 2009 Aug 21;325(5943):1006-10. PMCID:
PMC2766560. *Corresponding author
10. Mohammed Rafii-El-Idrissi Benhnia, Megan McCausland, John Laudenslager, Steven W. Granger,
Sandra Rickett, Lilia Koriazova, Tomoyuji Tahara, Ralph T. Kubo, Shinichiro Kato and Shane Crotty*.
Heavily isotype dependent protective activities of human antibodies against the extracellular virion form
of vaccinia virus.” J. Virology. 2009 Dec;83(23):12355-67. PMCID: PMC2786738. *Corresponding
author
11. Juan Moyron, Megan McCausland, Robin Kageyama, Alessandro Sette and Shane Crotty*. “The
smallpox vaccine induces an early neutralizing IgM response.” Vaccine. 2009 Dec 10;28(1):140-7.
PMCID: PMC2788018. *Corresponding author
12. Shane Crotty*, Robert J. Johnston, and Stephen P. Schoenberger. "Effectors and memories: Bcl6 and
Blimp-1 in T and B lymphocyte differentiation." Nature Immunology. 2010 Feb 11(2):114-20. PMCID:
PMC2864556. *Corresponding author.
13. Amanda C. Poholek, Kyle Hansen, Sairy G. Hernandez, Danelle Eto, Anmol Chandele, Jason S.
Weinstein, Xuemei Dong, Jared M. Odegard, Susan M. Kaech, Alexander L. Dent, Shane Crotty, and
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Joe Craft. "In vivo regulation of Bcl6 and T follicular helper cell development." J. Immunology 2010.
185: 313-26. PMCID: PMC2891136
14. Isharat Yusuf, Robin Kageyama, Laurel Monticelli, Robert J. Johnston, Daniel DiToro, Kyle Hansen,
Burton Barnett and Shane Crotty*. “Germinal center T follicular helper cells require SLAM (CD150) for
IL-4 production.” J. Immunology 2010. 185:190-202. PMCID: PMC2913439 *Corresponding author
15. Shane Crotty. "Follicular helper CD4 T cells (Tfh)." Annual Reviews in Immunology. 2011. 29:621-63.
16. Youn Soo Choi, Robin Kageyama, Danelle Eto, Tania C. Escobar, Robert J. Johnston, Laurel
Monticelli, Christopher Lao, and Shane Crotty*. "ICOS receptor instructs T follicular helper- versus
effector-cell differentiation via induction of the transcriptional repressor Bcl6." Immunity. 2011. 34:93246. PMCID: PMC3124577 *Corresponding author.
17. Robert J. Johnston, Youn Soo Choi, Jeffrey A. Diamond, Jessica A. Yang, and Shane Crotty*. “STAT5
is a potent negative regulator of T FH differentiation.” J. Experimental Medicine. 2012 Feb
13;209(2):243-50 PMID: PMCID:3281266209 (7) *Corresponding author.
18. Mark A. Kroenke, Danelle Eto, Michela Locci, Michael Cho, Terence M. Davidson, Elias Haddad,
and Shane Crotty*. "Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell (Tfh)
differentiation." J. Immunology. 2012 Apr 15; 188(8) 3734-44 PMID: PMC3324673. *Corresponding
author.
D. Research Support:
Active
5U19AI090970-02 (P. Poignard, PI)
09/01/10 – 08/31/15
NIH/NIAID
Interplay of B cells and HIV that leads to broad neutralizing antibody responses
CROTTY PROJECT: Correlation of human broadly neutralizing antibodies to CD4 T cell help in HIV+
individuals
A small percentage of HIV+ individuals generate broadly neutralizing antibodies to HIV. Understanding how
the immune response in this subset of patients differs from the majority of HIV infected people is crucial for HIV
vaccine development and therapy. The major goals of this project are to determine whether development of
broadly neutralizing antibodies is correlated with less disrupted B lymphocyte compartments and follicular
helper CD4 T cells (Tfh) in two cohorts of longitudinally studied HIV+ patients.
5R01 AI072543-05 (S. Crotty, PI)
12/01/07-11/30/12
NIH/NIAID
Generation of long-term B cell memory and antibody responses to viral infections
It is vital to understand the role of CD4 T cells in germinal centers to understand how to better generate long
term humoral immunity to viruses. We now have an excellent system to examine this process, since we have
shown that SAP (SLAM-associated protein) plays a central role in CD4 T cell help at the germinal center stage
for the development of long term humoral immunity after a viral infection. In this project we study the functional
characteristics of CD4 T cells that provide B cell help, and the roles of SAP and SLAM-family receptors in this
process.
5U01 AI077953-04 (S. Crotty, PI)
04/01/08-03/31/12
NIH/NIAID
Therapeutic Fully Human Monoclonal Antibodies against Vaccinia Virus and Smallpox
The NIAID High Priority Biodefense Products list includes “High titer/concentrated Vaccinia Immune Globulin
(VIG) or replacement product based on monoclonal antibodies (mAbs)” as the first desired biodefense product.
Our project goal is to develop a highly efficacious, highly standardized fully human mAb replacement of VIG
that can be produced in large quantities and stored long term.
HHSN272200900044C (A. Sette, P.I.)
09/30/09-09/29/14
NIH/NIAID
The Identification of HLA Class II T cell epitopes from Mycobacterium Tuberculosis
Mycobacterium Tuberculosis (MTB) is the worldwide leading cause of death from infectious diseases. The
increasing incidence of drug resistant strains has heightened interest in the development of effective vaccines,
and prompted its inclusion in the list of A-C pathogens. The MTB genome encodes more than 4,000 different
Open Reading Frames (ORFs), generally highly conserved amongst different strains, including drug resistant
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Program Director/Principal Investigator (Last, First, Middle):
Crotty, Shane
ones. The present proposal addresses the systematic identification and validation of CD4+ T cell epitopes of
MTB binding to a panel of HLA class II molecules representative of the most common specificities expressed
worldwide. Our proposal is tailored to address important gaps in epitope knowledge that have been highlighted
in recent analysis of available data involving the TB research community. In particular, to address the issue
that human CD4+ T cell epitopes described to date are derived from only a small fraction of the MTB genome,
we will perform a truly unbiased genome-wide analysis of epitope reactivity, and determine the antigens from
which these epitopes are derived.
HHSN272200900048C (B. Peters, P.I.)
09/30/09-09/29/14
NIH/NIAID
B Cell Epitope Discovery and Mechanisms of Antibody Protection
The major goals of this project are to use combine immunological, structural, and bioinformatic techniques to
ascertain protective B cell epitopes against Vaccinia viruses. As part of this study, we will concurrently perform
crystallography to determine antibody-epitope specificity, generate new Vaccinia specific monoclonal
antibodies, and develop bioinformatic tools to predict antibody epitopes to assist in future vaccine
development.
HHSN272201200010C (A. Sette, P.I.)
12/15/11-12/14/12
NIH/NIAID
“Immune Epitope Database and Analysis Program”
Major Goal: The contract proposal relates to the maintenance and further development of the Immune Epitope
Database and associated analysis resource. Previously award as HHSN26620040006C
5R01AI063107-07 (S. Crotty, PI)
12/01/04 – 01/31/16
NIH/NIAID
Mechanisms of humoral immunity development and function to the smallpox vaccine
The major goals of this project are to continue our work examining the mechanisms of development of
neutralizing antibody responses to the smallpox vaccine, and the mechanisms of function of neutralizing
antibody responses to the smallpox vaccine.
1P01AI096187-01 (E. Hunter, PI)
07/07/11-06/30/12
NIH/NIAID
B-cell Biology of Mucosal Immune Protection from SIV Challenge
The major goals of this project are to determine if (1) two different candidate SIV vaccines are effective at
eliciting Tfh cells, (2) Tfh cells are elicited by two different candidate SIV vaccines in intestinal tissues, and (3)
do Tfh cell responses correlate with protection against a mucosal SIV challenge in the macaque model.
Completed
R01 AI063107-05 (S. Crotty, PI)
07/01/05 – 03/31/10
NIH/NIAID
Humoral immunity to vaccinia virus
Our specific aims are to determine: (1) Are there distinct functional subsets of human memory B cells? (2)
What are the interrelationships between the components of long term humoral immunity? (3) Is the memory B
cell recall response relevant for protection?
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