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A. Karolina Palucka, MD, PhD

 

 

 

 

 

EDUCATION

I am medical oncologist and have earned my M.D. in 1984 from Warsaw Medical Academy in Poland. This was followed by a Ph.D. in Hematology and Immunology in 1993 at the Karolinska Institute in Stockholm, Sweden. There I studied the mechanisms of resistance of leukemic cells to natural killer cells. Then I went to Paris, France for a post-doctoral fellowship in the laboratory of Professor Jean C. Gluckman at the Hopital Pitie-Salpetriere where  I studied cytokine regulation of dendritic cells/macrophages differentiation and function. I joined BIIR in 1998.

  

 

MAJOR CONTRIBUTIONS TO SCIENCE

Cancer patients are tolerant to their cancer via several mechanisms including i) deletion of immune effectors that could reject tumors (T, NK cells); and ii) their silencing through regulatory cells (CD4+ T, NKT cells). These immune effectors are under the control of dendritic cells (DC). Thus, because DCs control immunity they also represent attractive vectors for immunization against cancer. However, because DCs control tolerance they represent targets for tumor-mediated manipulation to insure immune escape and tumor development.  I have dedicated my scientific carrier to prove this concept and to utilize it to identify novel therapeutic targets and strategies in human cancer.

 

  • Type 1 interferon in the pathogenesis of systemic lupus erythematosis (SLE).  Blanco P, Palucka AK et al, Science 2001;294:1540-3.
  • Cross-regulation of TNF and type I interferon thus providing a mechanistic explanation for the appearance of lupus-like symptoms and titers of anti-double stranded DNA antibodies in patients on anti-TNF therapy. Palucka AK, et al. PNAS 2005;102:3372-7.
  • Pioneered the development of DC-based vaccine for the treatment of human cancers. Banchereau J, Palucka AK,. Cancer Res 2001;61:6451-8. Palucka AK, et al. J Immunother 2003;26:432-9.Paczesny S, …Palucka AK. J Exp Med 2004;199:1503-11. Palucka AK, et al. J Immunother 2005;28:158-68. Fay JW, Palucka AK, et al. Cancer Immunol Immunother 2006;55:1209-18. Palucka AK, et al. J Immunother 2006;29:545-57.
  • IL-6 as the molecular switch that regulates the differentiation of monocytes into macrophages or dendritic cells. Chomarat P, …Palucka AK. Nat Immunol 2000;1:510-4. Chomarat P, …. Palucka AK. J Immunol 2003;171:2262-9.
  • The biology of human DC subsets. Klechevsky E, et al. Immunity 2008;29:497-510.
  • Type 2 inflammation and the role of TSLP in breast cancer development and progression. Aspord C, ..Palucka, AK. J Exp Med 2007;204:1037-47. Pedroza-Gonzalez A, ….Palucka, AK. J Exp Med 2011;208:479-90.

 

 

CURRENT GRANTS

  • NIAID: U19 AIO89987: Palucka, A.K. (PI)
    06/01/10 – 05/31/15
    Systems Analysis of Vaccine Responses in Healthy and Hyporesponsive Humans
  • NIH: U01 AI095611: Merad, M (PI); Palucka, AK (PI)
    07/15/11 – 06/30/15
    Role of Mucosal DC Subsets in the Control of Influenza A Virus Immunity

 

 

PUBLICATIONS (total of 133 from 1987 to 2012)

 

Key publications during the past 5 years (2007 to 2012)

1.  Palucka, K and Banchereau, J (2012). Cancer immunotherapy via Dendritic cells. Nat Rev Cancer (in press)

 

2.  Pedroza-Gonzalez, A., Xu, K., Wu, T.C., Aspord, C., Tindle, S., Marches, F., Gallegos, M., Burton, E.C., Savino, D., Hori, T., Tanaka, Y., Zurawski, S., Zurawski, G., Bover, L., Liu, Y.J., Banchereau, J., and Palucka, A.K.  (2011).  Thymic stromal lymphopoietin fosters human breast tumor growth by promoting type 2 inflammation.  J Exp Med.  208:479-90. PMCID: PMC3058586

 

3.  Cobb, A., Roberts, L.K., Palucka, A.K., Mead, H., Montes, M., Ranganathan, R., Burkeholder, S., Finholt, J.P., Blankenship, D., King, B., Sloan, L., Harrod, A.C., Levy, Y., and Banchereau, J.  (2011). Development of a HIV-1 lipopeptide antigen pulsed therapeutic dendritic cell vaccine.  J Immunol Methods.  365:27-37. PMCID: PMC2767876.

 

4.  Frleta, D., YU, C.I., Klechevsky, E., Flamar, A.L., Zurawski, G., Banchereau, J., and Palucka, A.K.  (2009). Influenza virus and poly (I:C) inhibit MHC class I-restricted presentation of cell-associated antigens derived from infected dead cells captured by human dendritic cells.  J. Immunol. 182:2766-76.  PMCID: PMC2665125.

 

5.  Yu, C.I., Gallegos, M., Marches, F., Zurawski, G., Ramilo, O., Garcia-Sastre, A., Banchereau, J. and Palucka, A.K.  (2008).  Broad influenza-specific CD8+ T-cell responses in humanized mice vaccinated with influenza virus vaccines.  Blood.  12(9):3671-3678.  PMCID: PMC2752794.

 

6.  Klechevsky, E., Morita, R., Liu, M., Cao, Y., Coquery, S., Thompson-Snipes, L., Briere, F., Chaussabel, D., Zurawski, G., Palucka, A.K., Reiter, Y., Banchereau, J., and Ueno, H.  (2008).  Functional Specializations of Human Epidermal Langerhans Cells and CD14+ Dermal Dendritic Cells.  Immunity.  29:497-510. PMCID: PMC2688399. 

 

7.  Vence, L., Palucka, A.K., Connolly, J.E., Fay, J.W., Ito, T., Liu, Y-J., Banchereau, J., and Ueno, H. (2007). Circulating tumor antigen-specific regulatory T cells in patients with metastatic melanoma. PNAS. 104:20884-20889. PMCID: PMC2409236. 

 

8.  Ramilo, O., Allman, W., Chung, W., Mejias, A., Ardura, M., Glaser, C., Wittkowski, K.M., Piqueras, B., Banchereau, J., Palucka, A.K., and Chaussabel, D.  (2007).  Gene expression patterns in blood leukocytes discriminate with acute infections. Blood. 109:2066-2077.  PMCID: PMC1801073.  

 

9.  Dubsky, P., Saito, H., Leogier, M., Dantin, C., Connolly, J.E., Banchereau, J., and Palucka, A.K. (2007).  IL-15-induced human dendritic cells efficiently prime melanoma-specific naïve CD8+T cells to differentiate into CTL. Eur. J. Immunol. 37:1678-1690. 

 

10. Aspord, C., Pedroza-Gonzalez, A., Gallegos, M., Tindle, S., Burton, E.C., Su, D., Marches, F., Banchereau, J., and Palucka, A.K.  (2007). Breast cancer instructs dendritic cells to prime interleukin 13-secreting CD4+ T cells that facilitate tumor development. J. Exp. Med. 204:1037-1047.  PMCID: PMC2118566. 

 

 



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