John E CONNOLLY

Translational Immunology

Profile

John E CONNOLLY
Lab Location: #7-17   Email: jeconnolly@imcb.a-star.edu.sg   Tel: 65869652

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.

Research

1. PI CV

Curriculum Vitae
Current position and past employment history

  • 2013 - Present: Senior Principal Investigator, Institute of Molecular and Cell Biology
  • 2011-  Present : Director ASPIRE, A*Star Programme in Translational Research on Infectious Disease (http://www.aspire.a-star.edu.sg)
  • 2010- Present: Director Programme in Translational Immunology
  • 2010 - 2013: Principal Investigator, Singapore Immunology Network
  • 2009 - 2010: Director for Research Initiatives, Baylor Research Institute
  • 2008 - Present: Adjunct Associate Professor of Biomedical Studies, Baylor University Medical Center, Waco, TX
  • 2005 - 2008: Adjunct Assistant Professor of Biomedical Studies, Baylor University Medical Center, Waco, TX
  • 2003 - 2008: Assistant Investigator, Baylor Institute for Immunology Research, Dallas, TX
  • 2001 - 2003: Research Associate, Dartmouth Medical School, Department of Immunology and Microbiology, with Drs. Paul K. Wallace and Michael W. Fanger

Academic Qualifications:

  • 1995 - 2001: Graduate Student, Dartmouth Medical School Department of Biochemistry, in the lab of Dr. William Rigby
  • 1994: Undergraduate Senior Research, Framingham State College, Department of Chemistry, Framingham, MA
  • 1993: Undergraduate Senior Research, Framingham State College, Department of Biology, Framingham, MA
  • 1993: Research Assistant, United States Army Research, Development and Engineering Labs, Department of Biotechnology, Natick, MA

2. Research Activities

Scientific Societies:

  • American Cancer Society North Texas Region; Board of Directors, President of the Board
  • American Association of Immunologists
  • American Society for Reproductive Immunology
  • Clinical Immunology Society
  • Federation of Clinical Immunologists
  • International Society for Interferon and Cytokine Research

 

Staff

Department: John E CONNOLLY

Name: Nivashini KALIAPERUMAL

Designation: Research Officer

Email: nivashinik@imcb.a-star.edu.sg


Name: Najwa Binte Said Nasir TALIB

Designation: Research Officer

Email: talibn@imcb.a-star.edu.sg


Name: Patricia Jennifer AHL

Designation: Research Officer

Email: ajpatricia@imcb.a-star.edu.sg


Name: Veonice Bijin AU

Designation: Senior Research Officer

Email: bjau@imcb.a-star.edu.sg


Name: Shi'en, Reina SNG

Designation: Research Officer

Email: sngse@imcb.a-star.edu.sg


Name: Angeline GOH

Designation: Research Scientist (Euchloe)

Email: agoh@imcb.a-star.edu.sg


Name: Kar Wai TAN

Designation: Senior Research Scientist (Euchloe)

Email: kwtan@imcb.a-star.edu.sg


Name: Sven Hans PETERSEN

Designation: Senior Research Scientist

Email: petersensh@imcb.a-star.edu.sg


Name: Keh Chuang CHIN

Designation: Senior Scientist

Email: kcchin@imcb.a-star.edu.sg


Name: Xavier Francois Noel CAMOUS

Designation: Research Fellow

Email: xcamous@imcb.a-star.edu.sg


Name: Lay Hoon LEE

Designation: Senior Research Officer

Email: leelh1@imcb.a-star.edu.sg


Name: Anshula ALOK

Designation: Research Fellow

Email: aalok@imcb.a-star.edu.sg


Name: Abrar Al-Mahmood SIDDIQUEE

Designation: Research Officer

Email: abrarams@imcb.a-star.edu.sg


Name: John Edward CONNOLLY

Designation: Research Director

Email: jeconnolly@imcb.a-star.edu.sg


Name: Chrissie LIM

Designation: Research Fellow

Email: chlim@imcb.a-star.edu.sg


Name: Sriram NARAYANAN

Designation: Senior Research Fellow

Email: sriramn@imcb.a-star.edu.sg


Name: Dang VU L

Designation: Senior Research Scientist

Email: dangvul@imcb.a-star.edu.sg


Name: Cheah Chen SEH

Designation: Research Scientist (Euchloe)

Email: ccseh@imcb.a-star.edu.sg


Name: Rujun GUAN

Designation: Research Engineer

Email: rguan@imcb.a-star.edu.sg


Name: Sonia Maria Pinhiero MAIA

Designation: Research Assistant

Email: soniam@imcb.a-star.edu.sg


Name: Wen Wei XIANG

Designation: Data Scientist

Email: wwxiang@imcb.a-star.edu.sg


Name: Wai Ling CHAN

Designation: Lab Management Support

Email: chanwl@imcb.a-star.edu.sg


Name: Victor Christoff DE VRIES

Designation: Senior Research Scientist

Email: victorc@imcb.a-star.edu.sg


Name: Hui Yin LEE

Designation: Senior Research Officer

Email: leehy@imcb.a-star.edu.sg


Name: Joni Choy Yue CHONG

Designation: Principal Scientist I

Email: cychong@imcb.a-star.edu.sg


Name: Marius Ciprian JONES

Designation: Senior Research Fellow

Email: mcjones@imcb.a-star.edu.sg


Name: Olivier Nicolas Felix CEXUS

Designation: Research Fellow

Email: onfcexus@imcb.a-star.edu.sg


Name: Zi Xin WONG

Designation: Research Officer

Email: zxwong@imcb.a-star.edu.sg


Name: Wei Yee ONG

Designation: Research Officer

Email: wyong@imcb.a-star.edu.sg


Name: Yi Fang Catherine CHONG

Designation: Business Development Manager

Email: chongyf@imcb.a-star.edu.sg


Name: Richard HOPKINS

Designation: Research Director

Email: rhopkins@imcb.a-star.edu.sg


Publications

PI PUBLICATIONS

2013

Andiappan AK, Puan KJ, Lee B, Nardin A, Poidinger M, Connolly J, Chew F, Wang DY, Rotzschke O.
Allergic airway diseases in a tropical urban environment are driven by dominant mono-specific sensitization against house dust mites.
In Press.  Allergy 2013

Chan KR, Ong EZ, Tan HC, Zhang SL, Zhang Q, Tang KF, Kaliaperumal N, Lim A, Hibberd ML, Chang SH, Connolly JE, Lok SM, Hanson BJ, Lina C, and Ooi EE. 
Leukocyte immunoglobulin-like receptor B1 is critical for antibody-dependent dengue.
In Press. PNAS 2013

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.

Manuel SL, Sehgal M, Connolly J, Makedonas G, Khan ZK, Gardner J, Betts MR, Jain P.
Lack of Recall Response to Tax in ATL and HAM/TSP Patients But Not in Asymptomatic Carriers of Human T-cell Leukemia Virus Type 1.
J Clin Immunol. 2013 Jul 26. [Epub ahead of print]

Chang YH, Connolly J, Shimasaki N, Mimura K, Kono K, Campana D.
A Chimeric Receptor with NKG2D Specificity Enhances Natural Killer Cell Activation and Killing of Tumor Cells. Cancer Res.2013 Mar 15;73(6):1777-86.

2012

Hwang SH, Lee H, Yamamoto M, Jones LA, Dayalan J, Hopkins R, Zhou XJ, Yarovinsky F, Connolly JE, Curotto de Lafaille MA, Wakeland EK, Fairhurst AM.
B Cell TLR7 Expression Drives Anti-RNA Autoantibody Production and Exacerbates Disease in Systemic Lupus Erythematosus-Prone Mice.
J Immunol. 2012 Dec 15;189(12):5786-96.

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 Nov 30;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 Oct;96(1):32-5.

Haniffa M, Shin A, Bigley V, McGovern N, Teo P, See P, Wasan PS, Wang XN, Malinarich F, Malleret B, Larbi A, Tan P, Zhao H, Poidinger M, Pagan S, Cookson S, Dickinson R, Dimmick I, Jarrett RF, Renia L, Tam J, Song C, Connolly J, Chan JK, Gehring A, Bertoletti A, Collin M, Ginhoux F.
Human Tissues Contain CD141(hi) Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103(+) Nonlymphoid Dendritic Cells.
Immunity. 2012 Jul 27;37(1):60-73.

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

2011

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

Rahman S, Connolly JE, Manuel SL, Chehimi J, Montaner LJ, Jain P.
Unique Cytokine/Chemokine Signatures for HIV-1 and HCV Mono-infection versus Co-infection as Determined by the Luminex® Analyses.
J Clin Cell Immunol. 2011 Jan 7;2(1).

Rathore AP, Paradkar PN, Watanabe S, Tan KH, Sung C, Connolly JE, Low J, Ooi EE, Vasudevan SG. Celgosivir treatment misfolds dengue virus NS1 protein, induces cellular pro-survival genes and protects against lethal challenge mouse model.
Antiviral Res. 2011 Dec;92(3):453-60.

Garcia-Romo GS, Caielli S, Vega B, Connolly J, Allantaz F, Xu Z, Punaro M, Baisch J, Guiducci C, Coffman RL, Barrat FJ, Banchereau J, Pascual V.
Netting neutrophils are major inducers of type I IFN production in pediatric systemic lupus erythematosus.
Sci Transl Med.
2011 Mar 9;3(73):73ra20

2009-2006

Matsui, T., *Connolly, J.E., Michnevitz, M., Chaussabel, D., Tindle, S., Freitas, H., Piqueras, B., Banchereau, J., and Palucka, A.K.
CD2 distinguishes two subsets of human plasmacytoid dendritic cells with distinct phenotype and functions. (2009)
J Immunol Jun. 1;182(11):6815-23.

Gill MA, Long K, Kwon T, Muniz L, Mejias A, Connolly, J., Roy L., Banchereau J., Ramilo O.
Differential recruitment of dendritic cells and monocytes to respiratory mucosal sites in children with influenza virus or respiratory syncytial virus infection. (2008)
J Infect Dis. Dec 1;198(11):1667-76.

DiPucchio, T., Chatterjee, B., Smed-Sorensen, A., Clayton, S., Palazzo, A., Pypaert, M., Mellman, I., Banchereau, J., and Connolly, J.E.
Plasmacytoid dendritic cells directly cross-present viral antigens to MHC class-I in a proteasome-independent fashion. (2008)
Nature Immunology.
May; 9, 551 - 557 (2008).

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

Touma M, Antonini V, Kumar M, Osborn SL, Bobenchik AM, Keskin DB, Connolly J.E., Grusby MJ, Reinherz EL, Clayton LK
Functional role for IkappaBNS in T cell cytokine regulation as revealed by targeted gene disruption. (2007) J.Immunol. Aug 1;179(3):1681-92

Mejías, A., Chávez-Bueno1, S., Raynor M.B., Connolly, J.E., Kiener, P.A., Jafri1, H.A. and Ramilo, O., (2007) Motavizumab, an enhanced anti-Respiratory Syncytial Virus (RSV) neutralizing monoclonal antibody significantly modifies the local and systemic cytokine responses induced by RSV in the mouse model. (2007)
Virology. Oct 25;4(1):109

Connolly, J.E., Chaussabel, D., Banchereau, J., Dendritic cell and pathogen interactions in the subversion of protective immunity, (2007)
The Biology of Dendritic Cells in HIV Infection.
Gessani S., Belardelli, F., eds. Springer press.

Dhodapkar, K. M., Banerjee, D., Connolly, J.E., Eleyana, M., Bonvini, E., Ravetch, J.V., Steinman, R. M., Dhodapkar, M. (2007)
Induction of type I interferon response genes by selective engagement of activating Fcg receptors in human dendritic cells.
J Exp Med.
2007 May 14

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

Chang, D.H., Osman, K., Connolly, J., Kukreja, A., Krasovsky, J., Pack, M., Hutchinson, A., Geller, M., Liu, N., Annable, R., Shay, J., Kirchhoff, K., Nishi, N., Ando, Y., Hayashi, K., Hassoun, H., Steinman, R.M., and Dhodapkar, M.V. (2005).
Sustained expansion of NKT cells and antigen-specific T cell after injection of {alpha}-galactosyl-ceramide loaded mature dendritic cells.
J. Exp. Med. 201:1503-17.