Associate Professor
UC Davis
One Shields Avenue
Rm 3327 Tupper Hall
Davis, CA 95616
Tel: (530) 752-6785
Lab: (530) 752-3131
FAX: (530) 752-8692
blshacklett@ucdavis.edu

Cook College, Rutgers University — B.S., Microbiology (1985)
UC Davis — Ph.D., Microbiology (1994)
Institut Cochin de Génétique Moléculaire, Paris — Postdoctoral Fellowship, Molecular Virology (1994-1997)
Aaron Diamond AIDS Research Center (ADARC), Rockefeller University, New York — Postdoctoral Fellowship, Cellular Immunology (1997-2000)
Staff Research Investigator, Gladstone Institute of Virology and Immunology, UC San Francisco (2001-2003)

Honors and Awards
Selman A. Waksman Award in Microbiology, Rutgers University (1985)
Regents Predoctoral Fellowship, UC Davis (1988-1990)
Earle C. Anthony Predoctoral Fellowship, UC Davis (1990-1991)
Postdoctoral Fellowship, Agence Nationale de Recherches sur le SIDA (ANRS) (1994-1996)
Postdoctoral Fellowship, Fondation pour la Recherche Médicale (SIDACTION) (1996-1997)

Society Memberships
Society for Mucosal Immunology (SMI)
American Association of Immunologists (AAI)
American Society for Microbiology (ASM)
International AIDS Society (IAS)

Link to Dr. Shacklett's Community of Science Web Page

Bill Critchfield, Ph.D., Assistant Project Scientist
April Ferre, B.S., Ph.D. Candidate, Microbiology
Timothy Hayes, B.S., Ph.D. Candidate, Immunology
Donna Lemongello, B.S., Staff Research Associate
Bridget McLaughlin, M.S., Analyst
Julie Shaw, Ph.D. Student, Microbiology
Jennie Hui-Yan Zhang, Student Assistant
Delandy Young, B.S., Staff Research Associate 

Lab affiliates
Melissa Schreiber, P.A., Clinical Research Coordinator

Visitors and alumni
Vidya Atluri, Rotation Student (Microbiology Graduate Group), 2006
Jesse Deere, Rotation Student (Microbiology Graduate Group), 2005
Máire Quigley (Karolinska Institutet, Stockholm, Sweden), Visiting Graduate Student, 2005
Mohanakrishnan Janardhanan, M.S. (YRG CARE HIV Laboratory, Chennai, India), Visiting Scientist, 2006
Alix Scholer (Ecole Normale Supérieure, Paris, France), Summer Intern, 2004

Areas of investigation
Our research group focuses on cell-mediated immune responses to HIV and other viruses in mucosal tissues, and trafficking of lymphoid cells to mucosal tissues and the central nervous system.

Significance
Most studies of antiviral immunity have focused on peripheral blood. However, the majority of lymphocytes are harbored in lymphoid tissues throughout the body. Mucosal lymphoid tissues serve as a portal of entry for HIV and as a site of active viral replication and CD4+ T-cell depletion. Therefore, studies of mucosal immunity are of particular importance for our understanding of HIV pathogenesis. Understanding the induction of antiviral immunity at mucosal surfaces is also of great relevance for vaccine development, as the majority of HIV transmission occurs through sexual contact.

Approaches
We have established methods to detect antigen-specific T cells in mucosal tissues using clinical samples obtained by minimally invasive methods. We use a combination of approaches including flow cytometry, cellular immunology, and molecular biology, to study the trafficking patterns and effector functions of antigen-specific T cells. These translational research projects involve active collaborations with clinicians at UC Davis Medical Center and the University of California, San Francisco.

Contributions
• Development of methods and approaches to study antiviral immunity in mucosal tissues during natural infection (i.e., HIV) and after vaccination
• Identification of HIV and CMV-specific CD8+ T cells in gut-associated lymphoid tissue
• Development of flow cytometric methods to assess T cell trafficking to cerebrospinal fluid
• Development of live, attenuated simian immunodeficiency viruses to study correlates of protective immunity to HIV/SIV in nonhuman primates

Questions addressed in ongoing studies
• What are the effector functions of antiviral T-cells in mucosal tissues?
• What is the relationship between CD8+ T cell frequency and HIV viral load in tissues?
• What molecules (i.e., integrins, chemokines) are involved in the trafficking of antigen-specific T cells to mucosal tissues and to the central nervous system?
• How do immunization routes correlate with the induction of antiviral T cell responses in tissues?

Shacklett BL, Cox CA, Sandberg JK, Jacobson MA, Stollman NH, Nixon DF. Trafficking of HIV-1-specific CD8+ T-cells to gut-associated lymphoid tissue (GALT) during chronic infection. Journal of Virology 77:5621-5631. 2003

Shacklett BL, Yang O, Hausner MA, Elliott J, Hultin L, Price C, Fuerst M, Matud J, Hultin P, Cox C, Ibarrondo J, Wong J, Nixon DF, Anton P, Jamieson BD. Optimization of methods to assess human mucosal immune responses to HIV vaccination and infection. Journal of Immunological Methods 279:17-31. 2003

Chandwani R, Jordan KA, Shacklett BL, Papasavvas E, Rosenberg MG, Montaner LJ, Nixon DF, Sandberg JK. Immunodominance in the HLA-A2 restricted CD8 T cell response to Nef in HIV-1 infected children and adults. Scandinavian Journal of Immunology, 59:109-14. 2004

Karlsson RK, Nixon DF, Shacklett BL. Poorly soluble peptides can mimic authentic ELISPOT responses (Research Letter). Journal of Immunological Methods, 285:89-92. 2004

Shacklett BL, Cox CA, Wilkens DT, Karlsson RK, Nilsson A, Nixon DF, Price RW. Increased adhesion molecule and chemokine receptor expression on CD8+ T-cells trafficking to cerebrospinal fluid in HIV infection. Journal of Infectious Diseases 189:2202-12. 2004

Shacklett BL, Cox CA, Quigley M, Kreis C, Stollman NH, Jacobson MA, Andersson J, Sandberg JK, Nixon DF. Abundant granzyme A, but not perforin, in cytolytic granules of CD8+ T-cells in gut-associated lymphoid tissue (GALT): Implications for immune control of HIV-1 infection. Journal of Immunology 173:641-8. 2004

Roland ME, Neilands TB, Krone MR, Katz MH, Grant R, Busch MP, Hecht F, Shacklett BL, Kahn JO, Bamberger JD, Coates TJ, Martin JN. Seroconversion following non-occupational post-exposure prophylaxis against human immunodeficiency virus. Clinical Infectious Diseases 41:1507-13. 2005

Nixon DF, Deeks SG, Shacklett BL, Karlsson AC. Multidrug-resistant, dual-tropic HIV-1 and rapid progression (correspondence). Lancet 365:1924-5. 2005

Quigley MF, Abel K, Miller CJ, Zuber B, Sandberg JK, Shacklett BL. Perforin expression in the gastrointestinal mucosa is limited to acute simian immunodeficiency virus infection. Journal of Virology 80:3083-7. 2006

Zuber B, Quigley MF, Critchfield JW, Shacklett BL, Abel K, Miller CJ, Morner A, Paulie S, Ahlborg N, Sandberg, JK. Detection of macaque perforin expression and release by flow cytometry, immunohistochemistry, ELISA and ELISpot. J. Immunol. Methods 312:45-53. 2006

Guadalupe M, Reay E, Sankaran S, George MD, Verhoeven D, Shacklett BL, Flamm J, Prindiville T, Dandekar S. Improved restoration of mucosal immunity following initiation of HAART during primary HIV-1 infection. Journal of Virology 80:8236-47. 2006

Critchfield JW, Lemongello D, Walker DH, Garcia JC, Asmuth DM, Pollard RB, Shacklett BL. Multifunctional HIVgag specific CD8+ T-cell responses in rectal mucosa and PBMC during chronic HIV-1 infection.  Journal of Virology 81:5460-71. 2007.

Sparger, E.E., Dubie, R.A., Shacklett, B.L., Cole, K.S., Montelaro, R.C., Chang, W., and Luciw, P.A., Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine, Virology, in press 2008

McLaughlin, B.E., Baumgarth, N., Bigos, M., DeRosa, S.C., Altman, J.D., Roederer, M., Nixon, D.F., Ottinger, J., Sinclair, E., Shacklett, B.L., Li, J., Beckett, L., and Asmuth, D.M. (2008), Validation of 9 color reagent panels to detect T cell subset cytokine responses across different instrument platforms, Submitted 2008

Emu, B., Sinclair, E., Hatano, H., Ferre, A., Shacklett, B.L., Martin, J.N., McCune, J.M, and Deeks, S.G., HLA type predicts functional T cell responses, but is not necessary for viral control among HIV elite controllers, Submitted 2008

Review articles and commentaries

Shacklett BL. Beyond 51Cr release: New methods for analyzing HIV-specific T-cell responses in peripheral blood and mucosal tissues. Clinical and Experimental Immunology 130:172-182. 2002

Shacklett BL, Shattock RJ. Mucosal Immunity to HIV-1: Changing Fashions in Basic Research and Vaccine Design. Mucosal Immunity Update 12(2):3-6. 2004

Shacklett BL. Understanding the lucky few: The conundrum of HIV-exposed, seronegative individuals. Current HIV/AIDS Reports, 3(1):26-31. 2006

Shacklett BL.  Can the new humanized mouse model give HIV research a boost?  PLoS Medicine Jan 15;5(1):e13, 2008

Book chapters
Shacklett BL, Nixon DF. Methods for detection of antigen-specific T cells by Enzyme-linked immunospot assay (ELISPOT), Ch. 28 in: ASM Manual of Molecular and Clinical Laboratory Immunology, 7th Edition, B. Detrick, R.G. Hamilton and S.D. Douglas, Eds., ASM Press, 1374 pp. 2006

Shacklett BL. HIV Infection of the Gastrointestinal Tract, in: Latent Infection by HIV-1 and Related Lentiviruses: New Approaches and Treatment Challenges, A. Brown, Ed., Transworld Research Network, in press 2008.

Shacklett BL, Lemongello D, Critchfield JW. Methods for isolating mucosal T cells, in: HIV Protocols, 2nd Ed., V.R. Prasad and G.V. Kalpana, Eds., Humana Press, in press 2008.

Shacklett BL, Lemongello D, Critchfield JW. Quantitating HIV-1-specific T-cell responses by ELISPOT and cytokine flow cytometry, in: HIV Protocols, 2nd Ed., V.R. Prasad and G.V. Kalpana, Eds., Humana Press, in press 2008.