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Welcome to the Integrated Department of Immunology at the University of Colorado - School of Medicine and National Jewish Health.

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Ross Kedl PhD

Associate Professor of Immunology


 Ross Kedl

 

 

 

 

  

Phone: (303) 270-2061
E-mail: ross.kedl@UCDenver.edu 
Dr. Kedl's National Jewish Health webpage

The activation of adaptive immune responses is critically dependent upon the activation of innate immune cells and mediators.  However, the precise innate signals and pathways that best negotiate the transition from innate to adaptive have yet to be elucidated.  A number of years of work have made it clear that the stimulation of innate pathways is alone insufficient for the eventual production of adaptive cellular immunity.  Mere stimulation of the one or more innate receptors does not recapitulate the bulk of the infectious process that leads to potent adaptive immunity.  Collectively the field has arrived at the conclusion that inflammation alone is a necessary, but insufficient, component of the eventual production of cellular immunity.  

Our lab is interested in this curious boundary between the innate and adaptive immune systems and seeks to elucidate signals and pathways emanating from the various families of innate receptors most efficiently mediate the transition to the adaptive cellular immune response.  In doing so, we seek to determine not only the basic rules of immunity, many of which remain elusive, but also to identify practical methods of intervention for the purposes of vaccine discovery, development and design.  Experimentally we have demonstrated a number of ways in which the innate pathways intersect with the TNF receptor/Ligand superfamily, resulting in potent T cell expansion, effector function, and memory generation.  These discoveries and novel vaccination methods are being applied to both viral and tumor model systems in an effort to develop clinically relevant methods of therapeutic vaccination against diseases such as chronic infections and cancer.

 

  • Ross M. Kedl, William A. Rees, David A. Hildeman, Brian Schaefer, John Kappler, and Philippa Marrack.  T cells compete for access to antigen bearing antigen presenting cells.  2000 Journal of Experimental Medicine, 192(8):1105-1113 
  • Ross M. Kedl, Michael Jordan, Terence Potter, John Kappler, Philippa Marrack, and Steven W. Dow.  CD40 stimulation accelerates deletion of tumor-specific CD8(+) T cells in the absence of tumor-antigen vaccination.  Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10811-6.
  • Ross M. Kedl, Brian C. Schaefer, John W. Kappler, and Philippa Marrack.  T cells down-modulate antigen/MHC complexes on antigen presenting cells in vivo. 2002  Nature Immunology 3(1):27-32
  • Brian C. Schaefer, Michele L. Scheafer, John W. Kappler, Philippa Marrack, and Ross M. Kedl.  Observation of antigen-dependent CD8+ T cell/dendritic cell interactions in vivo. 2002 International Immunology 214(2):110-22
  • Christie L. Doxsee, Tony R. Riter, Michael J Reiter, Shelia J. Gibson, John P. Vasilakos, and Ross M. Kedl. The Immune Response Modifier and TLR7 agonist S-27609 selectively induces IL-12 and TNFa production from CD11c+CD11b+CD8- dendritic cells 2003 Journal of Immunology 171(3):1156-1163.
  • Cory Ahonen, Christie L. Doxsee, Sean McGurran, Tony R. Riter, Randolph J. Noelle and Ross M. Kedl. Combined TLR and CD40 Triggering Induces Potent CD8+ T Cell Expansion with Variable Dependence on Type I IFN. 2004 Journal of Experimental Medicine 199: 775–784.
  • Ulrike Wille-Reece, Chang-you Wu, Barbara J. Flynn, Ross M. Kedl and Robert A. Seder. Immunization with HIV-1 Gag protein conjugated to aTLR7/8 agonist results in the generation of HIV-1 Gag specific Th1 and CD8+ T cell responses. 2005 Journal of Immunology 174:7676-7683
  • Ulrike Wille-Reece, Barbara J. Flynn, Karin Lore, Richard A. Koup, Ross M. Kedl, Joseph J. Mattapallil, Mario Roederer, Walter R. Weiss and Robert A. Seder.  Targeting HIV Gag protein conjugated to a TLR7/8 agonist improves the magnitude and quality of Th1 and CD8+ T cell responses in non-human primates. 2005 Proceedings of the National Academy of Sciences. 102(42):15190
  • Ulrike Wille-Reece, Barbara J. Flynn, Karin Loré, Richard A. Koup, Aaron P. Miles, Allan Saul, Ross M. Kedl, Joseph J. Mattapallil, Walter R. Weiss, Mario Roederer, and Robert A. Seder. Toll-like receptor agonists influence the magnitude and quality of memory T cell responses after prime-boost immunization in nonhuman primates. 2006 Journal of Experimental Medicine 203(5):1249-58.
  • Jennifer A. McWilliams, Sean M. McGurran, Steve W. Dow, Jill E. Slansky, and Ross M. Kedl. A modified TRP2 epitope generates high affinity tumor-specific T cells but does not mediate therapeutic efficacy.  2006 Journal of Immunology  177(1):155-161 .
  • Lance U’Ren, Ross Kedl, and Steven Dow. Vaccination with liposome--DNA complexes elicits enhanced antitumor immunity.  2006.  Cancer Gene Therapy 13(11):1033-44.
  • Phillip J. Sanchez, Catherine Haluszczak, Hideo Yagita, and Ross M. Kedl. Combined-TLR/CD40 Stimulation Mediates Potent Cellular Immunity by Regulating Dendritic Cell Expression of CD70 In Vivo.  2007 Journal of Immunology, 178:1564-1572
  • James J. Moon, H. Hamlet Chu, Marion Pepper, Stephen J. McSorley, Stephen C. Jameson, Ross M. Kedl, and Marc K. Jenkins.  Naïve CD4+ T cell frequency varies for different epitopes and predicts repertoire diversity and response magnitude.  2007 Immunity 27(2): 203-213.
  • Cory L. Ahonen, Anna Wasiuk, Shinichiro Fuse, Mary Jo Turk, Marc S. Ernstoff, Arief A. Suriawinata, James D. Gorham, Ross M. Kedl, Edward J. Usherwood, and Randolph J. Noelle.  Enhanced efficacy and reduced toxicity of multifactorial adjuvants compared to unitary adjuvants as cancer vaccines.  2008  Blood 111:3116-3125.
  • Catherine Haluszczak, Adovi D.  Akue, Sara E.  Hamilton, Lindsey Pujanauski, Lenka Teodorovic, Lisa D.S.  Johnson, Stephen C.  Jameson, and Ross M.  Kedl. The naive antigen-specific CD8+ T cell repertoire contains memory phenotype cells that bear the signature of homeostatic expansion.  2009  Journal of Experimental Medicine 206(2):435.
  • Cubillos-Ruiz, Juan R., Xavier Engle, Uciane K. Scarlett, Diana Martinez, Amorette Barber, Raul Elgueta, Li Wang, Yolanda Nesbeth, Yvon Durant, Andrew T. Gewirtz, Charles L. Sentman, Ross Kedl, and Jose R. Conejo-Garcia.  Polyethylenimine-Based Sirna Nanocomplexes Reprogram Tumor-Associated Dendritic Cells Via Tlr5 to Elicit Therapeutic Antitumor Immunity.   2009 Journal of Clinical Investigation 119 (8): 2231-44.
  • Ross M. Kedl.  Revolving Doors: from academia to industry and back again.  Nature Immunology 2009 10(3):227
  • Jennifer A. McWilliams, Phillip J. Sanchez, Catherine Haluszczak, Laurent Gapin and Ross M. Kedl, Multiple innate signaling pathways cooperate with CD40 to induce potent, CD70-mediated cellular immunity.  2010, Vaccine, 28:1468.
  • Jonathan S. Kurche, Phillip J. Sanchez, Catherine Haluszczak, Matthew A. Burchill, and Ross M. Kedl.  Comparison of OX40L and CD70 in the promotion of CD4+ T cell responses.  2010 Journal of Immunology. 185(4):2106-15.
  • Jason Z. Oh and Ross M. Kedl. Jason Z. Oh and Ross M. Kedl. The capacity to induce cross-presentation dictates the success of a TLR7 agonist-conjugate vaccine for eliciting cellular immunity.  2010 Journal of Immunology, 185(8):4602 


View of Recent Publications in PubMed

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 Matt Burchill

 Postdoctoral Fellow

 Catherine Haluszczak

  Lab Technician

 Nathan Pennock

  Graduate Student 

 Beth Tamburini

  Postdoctoral Fellow

Chantel.jpg



Chantel Maybach

Visiting High School Biology Teacher &

Visiting Scholar

 

Ross M. Kedl, PhD

Associate Professor, Integrated Department of Immunology

 

 

 

Dr. Kedl received his PhD in 1997 in the Department of Laboratory Medicine and Pathology at the University of Minnesota in Minneapolis. Before joining the Faculty at the University of Colorado, Dr. Kedl was at 3M Pharmaceuticals working in their small molecule immune response modifier program. In his three years there, he spearheaded efforts at developing novel vaccine adjuvants, resulting in numerous publications and patents in the area of vaccine technology. Dr. Kedl returned to the academic sector in 2004 by joining the faculty in the Integrated Department of Immunology at the University of Colorado Health Sciences Center and National Jewish Medical Research Center where he continues to pursue the discovery and development of novel and clinically applicable vaccine technology. He is also the founder of a start-up pharmaceutical company, ImmuRx Inc., which focuses on developing therapeutic vaccines against chronic infectious diseases, such as HIV and cancer.

 

 

 

Lab Protocols (Word doucuments)

 Founder Mice
CD70 KO Founders

 
Germline Pup!!

 Formal Strain Name Informal Strain Name Phenotype
 C57BL/6J  B6  Control
   B6/129 F1  Control
 B6SJLF-PtprcaPep3b/BoyJ  B6.SJL  Control
 B6Cr.129S4-Tnfsf7tm1Sug/Pgn  CD27 KO  CD27 deficient
 B6129PF2/ifnab  IFNaR KO  IFN receptor deficient
 129S6/SvEv-Stat1tm1Rds  STAT1 KO  STAT1 deficient
 129S6/SvEv-Stat4tm1Rds  STAT4 KO  STAT4 deficient
 B6Cr.129S4-Tnfsf4tm1Sug/Pgn  OX40 KO  OX40 deficient
 B6.129S2-H2dlAb1-Ea/J  Class II KO  Class Ii deficient
 B6.DTR-CD11c  CD11c DTR  conditional deletion of CD11c+ cells upon DT administration
 B6.DTR-FoxP3-GFP  DTR FoxP3  conditional deletion of FoxP3+ cells upon DT administration
 B6.FVB-Tg(Itgax-DTR/EGFP)57Lan/J  Lang DTR  conditional deletion of langerhans cells upon DT administration
 B6.FVB-Tg(Itgax-DTA/EGFP)Lan/J  Lang DTA  langerhans cell deletion
 C.129S1-Il12rb1tm1Jm/J  IL-12Rb1 KO  IL-12Rb1 deficient
 C.129S1-Il12rb2tm1Jm/J  IL-12Rb2 KO  IL-12Rb2 deficient
 C.129S1-Il23p19tm1Jm/J  IL-23p19 KO  IL23p19 deficient
 C.129S1-Il27rtm1Jm/J  IL-27R KO  IL-12 receptor deficient
 B6.129P2-Cd40tm1Kik/J  TRAF5 KO  TRAF5 deficient
 C57BL/6-Tg(TcraTcrb)1100MjB/J  OT1  ova specific TCR transgenic
   gB-T1  HSV gB-specific TCR transgenic
 B6;D2-Tg(TcrLCMV)327Sdz/JDvsJ  P14  LCMV GP TCR transgenic
 C57BL/6-Tg(TcraTcrb)425Cbn/J  OTII  ova specific CD4+ TCR transgenic
 B6.129P2(Cg)-MyD88tm1.1Defr/J  MyD88 KO  MyD88 deficient
 B6.129S1-Tlr7tm1Flv/J  TLR7 KO  TLR7 deficient
 B6;129S1-Tlr3tm1Flv/J  TLR3 KO  TLR3 deficient
 C57BL/6NTac-IL15tm1Imx  IL-15Ra KO  IL15R alpha deficient
 B6.129s4-il2rbtm1Dw/J  CD122 KO  CD122 deficient
 Prdm1gfp/gfp  Blimp-1-YFP  Blimp-1 expression of YFP
 129SvEvBatF3-/-  BatF3 KO  BatF3 transcription factor deficient
 B6;129P2-Rag1/Rag2tm1Mnz/J  Rag2 KO  Rag2 deficient
 B6.129p2-CD40<tm1Kik>/J  CD40 KO  CD40 deficient
 B6-Tnflsf7tm1  CD70 KO  CD70 deficient