Megan A. Cooper, M.D., Ph.D.

Associate Professor
Pediatrics
Rheumatology
Pathology and Immunology

Immunology Program
Human and Statistical Genetics Program

  • 314-286-0262

  • 314-286-0503

  • 8208

  • MPRB, 6th Floor

  • cooper_m@WUSTL.EDU

  • http://research.peds.wustl.edu/labs/cooper_m/

  • NK cells, interferon gamma IFN-y, autoimmunity, STAT3, immunology, pediatric

  • The biology of natural killer (NK) cells and immune defects in patients with autoimmunity

Research Abstract:

Our laboratory investigates two areas of immunology, the biology of natural killer (NK) cells and immune defects in patients with autoimmunity. First, we are interested in the development of NK cell memory and the regulation of NK cell interferon-gamma (IFN-y) production. NK cells are innate immune lymphocytes capable of recognizing and killing target cells and producing immunoregulatory cytokines, especially interferon gamma IFN-y. NK cells are important for the initial control of a variety of pathogens, and defects in NK cells lead to fatal infections. One classical distinction between innate immune cells, including NK cells, and adaptive immune cells (i.e., T and B cells) is the restriction of immunologic memory to adaptive immunity. Immune memory has two primary features: (1) the ability to respond to specific antigens and (2) an amplified immune response upon subsequent antigen exposure. We have demonstrated that in contrast to our current understanding of innate immunity, NK cells exhibit properties of immunologic memory. Utilizing an adoptive transfer system, NK cells with a history of prior cytokine activation were found to maintain an NK-intrinsic enhanced capacity to produce IFN-y upon re-stimulation. This “"memory-like" property of NK cells is not antigen specific and is unique among innate immune cells.

The second focus of our laboratory is the investigation of immune defects in pediatric patients with autoimmunity. Specifically, we are utilizing whole exome sequencing to identify candidate genes and pathways that contribute to pediatric autoimmune disease.

Selected Publications:

Mah AY, Rashidi A, Keppel MP, Saucier N, Moore EK, Alinger JB, Tripathy SK, Agarwal SK, Jeng EK, Wong HC, Miller JS, Fehniger TA, Mace EM, French AR, Cooper MA. Glycolytic requirement for NK cell cytotoxicity and cytomegalovirus control. JCI Insight. 2017;2(23): pii: 95128. doi: 10.1172/jci.insight.95128. *Featured Immunology article in “JCI This Month”, January 2018, https://insight.jci.org/this-month/2018/1

Ma CA, Stinson JR, Zhang Y, Abbott JK, Weinreich MA, Hauk PJ, Reynolds PR, Lyons JJ, Nelson CG, Ruffo E, Dorjbal B, Glauzy S, Yamakawa N, Arjunaraja S, Voss K, Stoddard J, Niemela J, Zhang Y, Rosenzweig SD, McElwee JJ, DiMaggio T, Matthews HF, Jones N, Stone KD, Palma A, Oleastro M, Prieto E, Bernasconi AR, Dubra G, Danielian S, Zaiat J, Marti MA, Kim B, Cooper MA, Romberg ND, Meffre E, Gelfand EW, Snow AL, Milner JD. Germline hypomorphic CARD11 mutations in severe atopic disease. Nat Genet. 2017. PMID:28628108

Lovric S, Goncalves S, Gee HY, Oskouian B, Srinivas H, Choi WI, Shril S, Ashraf S, Tan W, Rao J, Airik M, Schapiro D, Braun DA, Sadowski CE, Widmeier E, Jobst-Schwan T, Schmidt JM, Girik V, Capitani G, Suh JH, Lachaussée N, Arrondel C, Patat J, Gribouval O, Furlano M, Boyer O, Schmitt A, Vuiblet V, Hashmi S, Wilcken R, Bernier FP, Innes AM, Parboosingh JS, Lamont RE, Midgley JP, Wright N, Majewski J, Zenker M, Schaefer F, Kuss N, Greil J, Giese T, Schwarz K, Catheline V, Schanze D, Franke I, Sznajer Y, Truant AS, Adams B, Désir J, Biemann R, Pei Y, Ars E, Lloberas N, Madrid A, Dharnidharka VR, Connolly AM, Willing MC, Cooper MA, Lifton RP, Simons M, Riezman H, Antignac C, Saba JD, Hildebrandt F. Mutations in sphingosine-1-phosphate lyase cause nephrosis with ichthyosis and adrenal insufficiency. J Clin Invest. 2017;127(3):912-928. PMCID:PMC5330730 PMID:28165339

Milner, J. D., Vogel, T. P., Forbes, L., Ma, C. A., Stray-Pedersen, A., Niemela, J. E., Lyons, J. J., Engelhardt, K. R., Zhang, Y., Topcagic, N., Roberson, E. D., Matthews, H., Verbsky, J. W., Dasu, T., Vargas-Hernandez, A., Varghese, N., McClain, K. L., Karam, L. B., Nahmod, K., Makedonas, G., Mace, E. M., Sorte, H. S., Perminow, G., Rao, V. K., O`Connell, M. P., Price, S., Su, H. C., Butrick, M., McElwee, J., Hughes, J., Willet, J., Swan, D., Xu, Y., Santibanez-Koref, M., Slowik, V., Dinwiddie, D. L., Ciaccio, C. E., Saunders, C. J., Septer, S., Kingsmore, S. F., White, A. J., Cant, A. J., Hambleton, S., Cooper, M. A. (2015). Early-onset lymphoproliferation and autoimmunity caused by germline STAT3 gain-of-function mutations. Blood, 125 (4), 591-599. PubMed: 25359994.

Keppel, M. P., Saucier, N., Mah, A. Y., Vogel, T. P., Cooper, M. A. (2015). Activation-Specific Metabolic Requirements for NK Cell IFN-γ Production. J Immunol, 194 (4), 1954-1962 PubMed: 25595780.

Tarbox JA, Keppel MP, Topcagic N, Mackin C, Ben Abdallah M, Baszis KW, White AJ, French AR, Cooper MA. Elevated double negative T cells in pediatric autoimmunity. Journal of Clinical Immunology, 34 (5):594-599, 2014. PMID: 24760111.

Leong, J. W., Chase, J. M., Romee, R., Schneider, S. E., Sullivan, R. P., Cooper, M. A., Fehniger, T. A. (2014). Preactivation with IL-12, IL-15, and IL-18 Induces CD25 and a Functional High-Affinity IL-2 Receptor on Human Cytokine-Induced Memory-like Natural Killer Cells. Biol Blood Marrow Transplant, 20 (4), 463-73. PMCID: PMC3959288 PubMed: 24434782.

Lim E, Yu T, White AJ, French AR, Cooper MA. Hypogammaglobulinemia in Pediatric Systemic Lupus Erythematosus. Lupus, 22 (13): 1382-1387, 2013. PMID: 24106215.

Keppel MP, Yang L, Cooper MA. Murine NK cell intrinsic cytokine-induced memory-like responses are maintained following homeostatic proliferation. J. Immunol., 190 (9): 4754-4762, 2013. PMID: 23530145.

Cooper MA, Yokoyama WM. Memory-like responses of natural killer cells. Immunol Rev 2010 235: 297-305. PMID 20536571.

Romee R, Schneider SE, Leong JW, Chase JM, Keppel CR, Sullivan RP, Cooper MA, Fehniger TA. Cytokine activation induces human memory-like NK cells. Blood, 120 (24): 4751-4760, 2012. PMID: 22983442.

Last Updated: 7/25/2018 8:15:24 AM

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