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Philippa Marrack PhD

Distinguished Professor of Immunology & Microbiology, Ida & Cecil Green Professor and Chairman, Department of Biomedical Research at National Jewish Health


1400 Jackson St., Rm K512a
Denver, CO 80206
Phone:  303-398-1322
E-mail: marrackp@njhealth.org
Dr. Marrack's National Jewish Health webpage

We study lymphocytes, the cells which recognize that an infection is occurring in the body. Amongst these, we are particularly interested in T cells. They recognize infections in an unexpected way, by reacting with fragments of the infection bound to special proteins of the body, the MHC proteins. We are trying to find out how T cells learn to react in this fashion. We are also interested in the ways in which T cells are prevented from attacking MHC proteins bound to fragments of their own host. In most people such attack is efficiently avoided. However, in some individuals T cells do react in this way, and this event causes autoimmune diseases such as rheumatoid arthritis and juvenile diabetes. Our recent experiments suggest that the diseases occur because the peptide fragments involved are binding to MHC in an unexpected way.

B cells, the cells that produce antibodies, are also involved in autoimmune disease.. We have recently found an unusual population of B cells that might be involved in the process.

The power of the immune response is harnessed in vaccines, vaccines act by inducing T and B cell memory to protect us against invading organisms. We study how this is accomplished, with the hope that this understanding will help us design better vaccines.

  • Mack DG, Falta MT, McKee AS, Martin AK, Simonian PL, Crawford F., Gordon T, Mercer RR, Hoover MD, Marrack P, Kappler JW, Tuder RM and Fontenot AP.  Regulatory T cells modulate granulomatous inflammation in an HLA-DP2 transgenic murine model of beryllium-induced disease.  Proc. Natl. Acad. Sci USA 111:8553-8, 2014.  PMC4060652.
  • Rubtsova K, Marrack P and Rubstov AV.  Sexual dimorphism in autoimmunity.  J. Clin. Invest. 125:2187-93, 2015.  PMC4497744.
  • Rubtsova K., Marrack P and Rubtsov AV.  TLR7, IFNg and T-bet: their roles in the development of ABCs in female-biased autoimmunity.  Cell. Immunol. 294:80-83, 2015.  PMC4380581.
  • Atif SM, Nelsen M, Gibbings SL, Desch AN, Kedl R, Gill R, Marrack P, Murphy KM, Grazia TJ, Henson PM and Jakubzick C.  Cutting edge: Roles for BATF3-dependent antigen-presenting cells in rejection of cells or tissues with mismatched minor histocompatability antigens.  J Immunol. 195:46-50,  2015.  PMC4632856.
  • Rubtsov AV, Rubtsova K, Kappler JW, Jacobelli J, Friedman RS, Marrack P.  CD11c-Expressing B Cells Are Located at the T Cell/B Cell Border in Spleen and Are Potent APCs. J Immunol. 195:71-79, 2015.  PMC4475418
  • Rubtsova K, Cancro MP, Rubtsov A and Marrack P. Age Associated B Cells (ABCs) – origin, phenotype and function, in age, autommunity and virus infections.  J. Immunol. 195:1933-7, 2015. PMC4548292.
  • Liu H, White J,  Crawford F, Jin N, Ju X, liu K, Jiang C, Zhang G, Marrack P and Kappler JW.  A rapid method to characterize mouse IgG antibodies and isolate native antigen binding IgG B cell hybridomas.  PLoS One 10:e0136613, 2015.  PMC4552657.
  • Jin N, Wang Y, Crawford F, White J, Marrack P, Dai S, Kappler JW. N-terminal additions to the WE14 peptide of chromogranin A create strong autoantigen agonists in type 1 diabetes.  Proc. Natl. Acad Sci USA 112:13318-23, 2015.  PMC4629350
  • Noges LE, White J, Cambier JC, Kappler JW and Marrack P.  Contamination of DNase preparations confounds analysis of the role of DNA in alum adjuvanted vaccines.  J. Immunol. 197:1221-1230, 2016. PMC4974487.
  • Silberman D, Krovi SH, Tuttle KD, Crooks J, Reisdorph R, White J, Gross J, Matsuda JL, Gapin L, Marrack P and Kappler JW. Class II major histocompatibility complex mutant mice to study the germline bias of T cell antigen receptors.  Proc. Natl. Acad. Sci USA 113:E5608-17, 2016.  PMC 5035841.
  • Rubtsova, K, Rubtsov, AV Halemano K, Sam LX, Kappler JW, Sanitago ML and Marrack P.  T cell production of IFNg in response to TLR7/IL12 stimulates optimal B cell responses to viruses.  PLoS One  in press 2016.
  • MacLeod, M.K., Kappler, J.W. and Marrack, P.  Memory CD4 T cells: generation, reactivation and reassignment.  Immunology 130:10-15, 2010. PMC2855788.
  • Rubtsov, A.V., Rubtsova, K, Kappler, J.W. and Marrack, P.  Genetic and hormonal factors in female-biased immunity.  Autoimmun. Rev. 9:494-498, 2010.  PMC in  process
  • Munks, M.W., McKee, A.S., MacLeod, M.K.., Powell, R., Brinkmann, V., Zychlisky, A., Degen, J.L., Reisdorph, N.A., Kappler, J.W. and Marrack, P. Aluminum Adjuvants Elicit Fibrin-Dependent Extracellular Traps in vivo.  Blood 116:5191-5199, 2010.  PMC 3012537.
  • Macleod, M.K.L., David, A., McKee, A.S., Crawford, F., Kappler, J.W. and Marrack, P.  Memory CD4 T cells that express CXCR5 provide accelerated help to B cells.  J. Immunol. 186:2889-2896, 2011. PMC 3069687
  • MacLeod, M.K.L., McKee, A.S., David, A., Wang, J., Mason, R.J., Kappler, J.W. and Marrack, P.  Vaccine adjuvants Aluminum and Monophosphoryl lipid A provide distinct signals to generate protective cytotoxic memory CD8 T cells. Proc. Natl. Acad. Sci. USA 108:7914-7919, 2011. PMC 3093483.
  • Rubtsov, A.V., Rubtsova, K., Fischer, A., Meehan, R.T., Gillis, J.,Z., Kappler, J.W. and Marrack, P. Toll-like receptor 7 (TLR7)-driven accumulation of a novel CD11c+ B cell population is important for the development of autoimmunity.  Blood 118:1305-1315, 2011.  PMC3152497.
  • Yin L, Huseby E, Scott-Browne J, Rubtsova K, Pinilla C, Crawford F, Marrack P, Dai S and Kappler J.W.  A Single T Cell Receptor Bound to Major Histocompatibility Complex Class I and Class II Glycoproteins Reveals Switchable TCR Conformers.  Immunity. 35:23-33, 2011.  PMC3160269.
  • Scott-Browne, J. P., Crawford, F., Young, M.H., Kappler, J.W., Marrack, P*. and Gapin, L.*   Evolutionarily conserved features of the alpha/beta T cell receptor contribute to its MHC specificity.  Immunity 35:526-535, 2011.  PMC3245739.  * These authors contributed equally to the work.
  • Rubtsova K, Marrack P, Rubtsov AV.  Age-associated B cells: are they the key to understanding why autoimmune diseases are more prevalent in women?  Expert Rev. Clin. Immunol. 8:5-7, 2012.  PMC 3940262
  • Marrack, P. and Kappler, JW.  Do MHCII presented neo-antigens drive type-1 diabetes and other autoimmune diseases?  Cold Spring Harbor Prospectives in Biology  Diabetes CSH Laboratory Press  Bluestone J., Editor. In press 2012. PMC in process.
  • Yin, L, Scott-Browne, J, Kappler, JW, Gapin, L and Marrack, P.  T cells and their eons-old obsession with MHC.  Immunol. Revs. 250:49-60, 2012.  PMC in process.
  • Rubtsov AV, Rubtsova KV, Kappler JW and Marrack P.  TLR7 drives accumulation of ABCs and autoantibody production in autoimmune prone mice.  Immunol. Res. 55:210-216, 2013.  PMC 3935605.
  • Yin, L., Dai, S., Clayton, G., Gao, W., Wang, Y., Kappler, J. and Marrack, P. Recognition of self and altered self by T cells in autoimmunity and allergy.  Protein and Cell 4:8-16, 2013. PMC3951410.
  • Young MH, U’Ren L, Huang S, Mallevaey T, Scott-Browne J, Crawford F, Lantz O, Hansen TH, Kappler J, Marrack, P and Gapin, L.  MAIT cell recognition of MR1 on bacterially infected and uninfected cells.  PLoS One 8:e53789, 2013 PMC3544856
  • McKee AS, Burchill MA, Munks MW, Jin L, Kappler J, Friedman RS, Jacobelli J and Marrack P.   Host DNA released in response to aluminum adjuvant prolongs CD4 T cell interactions with dendritic cells.  Proc. Natl. Acad. Sci, USA 110:E1122-31, 2013. PMC3607057.
  • Clambey ET, Collins B, Young MH, Eberlein J, David A, Kappler JW, Marrack P. The Ikaros transcription factor regulates responsiveness to IL-12 and expression of IL-2 receptor alpha in mature, activated CD8 T cells. PLoS One. 8: e57435, 2013. PMC3585008.
  • MacLeod MKL. David A, Jin N, Noges L, Wang J, Kapper JW and Marrack P.  Viral nucleoprotein delivered with aluminum salts protects mice from heterotypic influenza A infection.  PLoS One 8:e61775, 2013. PMC3629017.
  • Rubtsova K., Rubtsov AV., van Dyk  L, Kappler, J.W. and Marrack, P.  T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearance.  Proc. Natl. Acad. Sci. USA 110:E3216-24, 2013. PMC3752276.
  • Bedel R, Berry R, Mallevaey T, Matsuda JL, Zhang J, Godfrey DI, Rossjohn J, Kappler JW, Marrack P and Gapin L. Effective functional maturation of iNKT cells is constrained by negative selection and TCR affinity.  Proc. Natl Acad. Sci USA 111:E119-28, 2014 PMC3890789.
  • David A, Trigunaite A, MacLeod MKL, Johnson AC, Marrack P and Jorgensen TN. Intrinsic autoimmune capacities of hematopoietic cells from female New Zealand hybrid mice.  Genes and Immunity 15:153-161 2014.  PMC in process.
  • David A, Crawford F, Garside P, Kappler JW, Marrack P and MacLeod MKL.  Tolerance induction in memory CD4 T cells requires two rounds of antigen specific activation.  Proc. Natl. Acad. Sci, USA 111:7735-40, 2014.  PMC in process.
  • Mack DG, Falta MT, McKee AS, Martin AK, Simonian PL, Crawford F, Gordon T, Mercer RR, Hoover MD, Marrack P, Kappler JW, Tuder RM, Fontenot AP. Regulatory T cells modulate granulomatous inflammation in an HLA-DP2 transgenic murine model of beryllium-induced disease.  Proc Natl Acad Sci U S A. 111:8553-8, 2014.  PMC4060652
  • Clayton GM, Wang Y, Crawford F, Novikov A, Wimberly BT, Kieft JS, Falta MT Bowerman NA, Marrack P, Fontenot AP, Dai S and Kappler JW.  The structural basis of chronic beryllium disease: linking allergic hypersensitivity and autoimmunity.  Cell 158:132-42. 2014.  PMC4060652.

Link to PubMed for more papers

 

2016: Novartis Prize for Immunology
2015: Elected to National Women's Hall of Fame, USA
2015: Wolf Prize, Israel
2012: Visiting Professor, Graduate School of Medicine, Chiba University, Japan
2011: Election to rank of AAAS Fellow
2010: Election to Colorado Women's Hall of Fame
2008: Member, Institute of Medicine
2005: Rockefeller University Pearl Meister Greengard Prize.
2004: National Jewish Health Abraham J. Kauvar Presidential Award
2004: University of Colorado Health Sciences Center, School of Medicine, Mentoring Award
2004: L’Oreal UNESCO for Women in Science Award
2003: Faculty Ambassador Award, National Jewish Health
2000: Lifetime Achievement Award, American Association of Immunologists
2001: Irvington Institute Scientific Leadership Award in Immunology
1999: Interscience Conference on Antimicrobial Agents and Chemotherapy Award
1999: University of Chicago, Howard Taylor Ricketts Prize
1998: The Rabbi Shai Schacknai Memorial Prize
1997-   Fellow of the Royal Society
1996: Honorary Doctorate of Sciences, Macalester College
1995: Dickson Prize in Medicine, University of Pittsburgh
1995: Behring-Heidelberger Lecture Award
1995: FASEB Excellence in Science Award
1995: The Louisa Gross Horwitz Prize-Columbia University
1993: The Paul Ehrlich and Ludwig Darmstädter Prize, Germany
1993: Cancer Research Institute''s 1993 William B. Coley Award for Distinguished Research in Fundamental Immunology
1992: The Ernst W. Bertner Memorial Award, MD Anderson Cancer Center
1991: Honorary Doctorate of Sciences, University of Rochester
1989-   Member, National Academy of Sciences, USA