John E CONNOLLY   
                       
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  John E CONNOLLY  
  Lab Location: #07-17

email:
jeconnolly@imcb.a-star.edu.sg
tel: 65869652
 
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  Key Publications  
 


Chia WK, Teo M, Wang WW, Lee B, Ang SF, Tai WM, Chee CL, Ng J, Kan R, Lim D, Tan SH, Ong WS, Cheung YB, Tan EH, Connolly JE, Gottschalk S, and Han-Chong Toh. 
Adoptive T-cell transfer and chemotherapy in the first-line treatment of metastatic and/or locally recurrent Nasopharyngeal Carcinoma.  Molecular Therapy; 2013.242 Oct.

Skibinski D, Hanson B, Lin Y, von Messling V, Jegerlehner A, Sern Tee JB, Chye DH, Wong S, Ng A, Lee HY, Au B, Lee B, Poidinger M, Santoso L, Fairhurst A-M, Matter A, Bachmann M, Saudan P, Connolly JE. 
Enhanced neutralizing antibody titers and Th1 polarization from a novel Escherichia coli derived pandemic influenza vaccine PLOSOne. November, 8; 10, 2013

Iyer JV, Connolly J, Yeo TK, Agrawal R, Lee B, Au B, Teoh SC.
Cytokine Analysis of Aqueous Humor in HIV Patients with Cytomegalovirus Retinitis. 
Cytokine 2013 Sept. 64; (2) 541-547

Edupuganti S, Eidex RB, Keyserling H, Akondy RS, Lanciotti R, Orenstein W, del Rio C, Pan Y, Querec T, Lipman H, Barrett A, Ahmed R, Teuwen D, Cetron M, Pulendran B, Caliendo A, Miller J, Easley K, Garg S, Lawson B, Frew PM, Skvarich J, Lalor S, Kirkendoll K, Furlow Z, Hotic M, Dennis R, Daugherty A, Bower M, Nesheim W, Nijem S, Anderson P, Hilinski J, Coote H, Osinski E, Connolly, J., and Mulligan MJ. 
A randomized, double-blind, controlled trial of the 17D yellow fever virus vaccine given in combination with immune globulin or placebo: comparative viremia and immunogenicity.
Am J Trop Med Hyg  2013  88(1) 172-7.

Ng AA, Lee BT, Teo TS, Poidinger M, Connolly JE.  Optimal cellular preservation for high dimensional flow cytometric analysis of multicentre trials.
J Immunol Methods. 2012  385 (1-2) 79-89

Watanabe S, Rathore AP, Sung C, Lu F, Khoo YM, Connolly J, Low J, Ooi EE, Lee HS, Vasudevan SG.  Dose and schedule-dependent protective efficacy of celgosivir in a lethal mouse model for dengue virus infection informs dosing regimen for a proof of concept clinical trial.
Antiviral Res. 2012   96 (1) 32-35.

Hopkins RA, Connolly JE.
The specialized roles of immature and mature dendritic cells in antigen cross-presentation.
Immunol Res.  2012  53 (1-3)  91-107

Hernández JG., Sundén F, Connolly JE, Svanborg C, Wullt B.
Genetic control of the variable innate immune response to asymptomatic bacteriuria. 
PLoS One. 
2011  6(11)  e28289.

Garcia G, Caielli S, Connolly JE, Allantaz F, Xu X, Punaro M, Coffman RL, Barratt FJ, Banchereau JB Pascual V.  Netting neutrophils induce type–I interferon production by plasmacytoid dendritic cells in systemic lupus erythematosus. 
Science, Translational Medicine; 2011  3 (73).

Matsui T, *Connolly JE, Michnevitz M, Chaussabel D, Tindle S, Freitas H, Piqueras B, Banchereau J, Palucka AK. 
CD2 distinguishes two subsets of human plasmacytoid dendritic cells with distinct phenotype and functions. 
J Immunol 2009  182 (11) 6815-23. 

DiPucchio T, Chatterjee B, Smed-Sorensen A, Clayton S, Palazzo A, Pypaert M, Mellman I, Banchereau J, Connolly, J.E. 
Plasmacytoid dendritic cells directly cross-present viral antigens to MHC class-I in a proteasome-independent fashion.
Nat. Immunol. 2008 (9)  551-7

Jiang A, Ono S, Jiang S, Whitney JA, Connolly JE, Banchereau J, Mellman I.  E-cadherin/B-catenin signaling defines a distinct pathway of dendritic cell maturation  Immunity  2007  27 (4) 610-24

Dendritic Cell Subsets in Health and Disease: Ueno H, Klechevsky E, Morita R, Aspord C, Cao T, Matsui T, Connolly JE, Palucka AK, Banchereau
J   Immunol. Rev. 2007  (219) 118-42

Dubsky P, Saito H, Leogier M, Dantin C, Connolly JE, Banchereau J, Palucka AK.  IL-15-induced human DC efficiently prime melanoma-specific naive CD8(+) T cells to differentiate into CTL. Eur J Immunol.  2007 37 (6) 168-90

Dhodapkar KM, Banerjee D, Connolly J, Kukreja A, Matayeva E, Veri MC, Ravetch JV, Steinman RM, Dhodapkar MV. 
Selective blockade of the inhibitory Fcgamma receptor (FcgammaRIIB) in human dendritic cells and monocytes induces a type I interferon response program. J Exp Med.  2007 204 (6) 1359-69

Palucka AK, Ueno H, Connolly JE, Kerneis-Norvell F, Blanck JP, Johnston DA, Fay J, Banchereau J.  Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity. 
J Immunother  2006  29(5) 545-57.

Piqueras B, Connolly J., Freitas H, Palucka AK, Banchereau J. 
Upon viral exposure myeloid and plasmacytoid dendritic cells produce three waves of distinct chemokines to recruit immune effectors. 
Blood  2006  107:2613-2618.

Banchereau J, Ueno H, Dhodapkar M, Connolly J, Finholt JP, Klechevsky E, Blanck JP, Johnston DA, Palucka AK, Fay J. 
Immune and clinical outcomes in patients with stage IV melanoma vaccinated with peptide-pulsed dendritic cells derived from CD34+ progenitors and activated with type I interferon.
J Immunother.  2005  28 (5):505-16

 
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    John E CONNOLLY
 


My interests lie in establishing a productive translational research program focusing on Dendritic Cell (DC) based immunotherapy. DCs form a critical link between the innate and adaptive immune response. During infection, DCs recognize and capture invading pathogens. The innate immune recognition of these pathogens drives DCs down a specific path of maturation. These mature, specialized DCs are then able to polarize the adaptive response toward distinct antipathogenic effector states, such as Th1, Th2 or Th17. Recently, research has indicated that in addition to inducing immune responses, polarized DCs play a critical role in maintaining self-tolerance. My primary research goals are directed toward understanding the role of human dendritic cell subsets in the induction of immunity and tolerance and exploiting this knowledge for the generation of novel vaccines.

The mechanism of receptor mediated internalization and downstream cargo sorting determines the immunologic outcome

       
    Translational Immunology
   


Program in Translational Immunology, Institute of Molecular and Cell Biology (IMCB)
The Program in Translational Immunology is dedicated to leveraging the basic research produced by A*Star scientists to make a quantifiable impact on patient care within Singapore. The program is based on three key principles 1. Fundamental studies in human immunology should have as their primary end point advances in medical care. 2. Translational immunology is a team effort between leaders, each contributing their own individual expertise. 3. Translational research is best achieved utilizing integrated, high quality core facilities and dedicated clinical support personnel.

The traditional academic model, with its individual focus and short term metrics of achievement cannot efficiently engage in, and in many ways is the antithesis of, successful translational research.

Structure of the Program
The operational structure of the program has been specifically designed to bridge the key gaps in access and training which prevent the movement fundamental research to a translational and clinical setting.

1. Immunomonitoring The ability to fully integrate complex data from multiple analytical modalities and to understand this data in the context of ongoing clinical progression is the central challenge in the field of translational immunology. Professionally managed, technology focused core facilities are the most effective way to ensure the high-level of data quality and reproducibility required for translational research. The Comprehensive Immunomonitoring Platform utilizes genomic, proteomic and novel cell based assays from multiple, integrated cores, to provide a complete picture of the human immune response during the course of disease or therapy. The platform employs data management and mining solutions for the optimal integration and exploitation of large volumes of patient specific data. This systems based approach is utilized for biomarker discovery, identifying novel points of therapeutic intervention and clinical trials monitoring.

2. Biobanking The scale, scope and multi-disciplinary nature of translational research dictates that a large quantity of carefully prepared, quality-assed biospecimens be available for study, and that the results of these studies be analyzed in the context of well curated, associated clinical data. A well regulated biobank therefore forms the central infrastructure component of modern translational research.

3. Clinical Support The normal flow of clinical practice leaves little time to dedicate to research. Clinical support infrastructure is therefore a critical aspect of a successful translational research program. Staff support such as dedicated research nurses and scientific writers form an important bridge from the active clinical team to the scientific research group. The implementation of clinical research database solutions which facilitate the accumulation, curation and analysis of anonymised patient associated data forms a second important measure. These databases offer the hospital systems, clinical departments and physician practices the ability to create long term, secure data repositories for ongoing and future clinical research.