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Ph.D. in Immunology & Experimental Therapy, Polish Academy of Sciences, (1995)

Expertise

Research Interests

My research is focused on uncovering cellular and molecular mechanisms of immune system with special emphasis on processes that regulate the development and functions of conventional and regulatory T cells. I am interested in how immune tolerance is established and preserved in healthy individuals and how tolerance mechanisms are subverted or alleviated to permit growth of tumor cells. The aim of ongoing, NIH funded projects is to reveal how inflammation associated with tumor growth modulates T cell functions in tumors. In particular, we investigate the involvement of connexin 43 and Bone Morphogenic Protein Receptor 1α in the generation of regulatory CD4+ T cells in the thymus and in the interplay between stromal cells and components of the innate and adaptive immune system in a mouse model of prostate cancer. The goal of our studies is to reveal and exploit novel mechanisms of immune regulation to overcome challenges facing immunotherapies of cancer.

Articles

Kuczma, M., Kurczewska, A. and Kraj, P. J. (2014). Modulation of bone morphogenic protein signaling in T-cells for cancer immunotherapy. J Immunotoxicol 11 (4) , pp. 319-27.

Cebula, A., Seweryn, M., Rempala, G. A.., Pabla, S. S.., McIndoe, R. A.., Denning, T. L.., Bry, L., Kraj, P. J., Kisielow, P. and Ignatowicz, L. (2013). Thymus-derived regulatory T cells contribute to tolerance to commensal microbiota. Nature 497 (7448) , pp. 258-62.

Kuczma, M., Lee, J. R.. and Kraj, P. J. (2011). Connexin 43 signaling enhances the generation of Foxp3+ regulatory T cells. J Immunol 187 (1) , pp. 248-57.

Friedman, D. F.., Kraj, P. J. and Silberstein, L. E.. (1995). VH4.21 expression in the normal human B-cell repertoire. Ann N Y Acad Sci 764 , pp. 285-92.

Kraj, P. J. (1997). Factors influencing the preimmune antibody repertoire. Folia Biol (Praha) 43 (2) , pp. 53-61.

Kraj, P. J., Pacholczyk, R., Ignatowicz, H., Kisielow, P., Jensen, P. and Ignatowicz, L. (2001). Positive selection of CD4(+) T cells is induced in vivo by agonist and inhibited by antagonist peptides. J Exp Med 194 (4) , pp. 407-16.

Kraj, P. J. and McIndoe, R. A.. (2005). caBIONet–A .NET wrapper to access and process genomic data stored at the National Cancer Institute’s Center for Bioinformatics databases. Bioinformatics 21 (16) , pp. 3456-8.

Kraj, P. J., Sharma, A., Garge, N., Podolsky, R. and McIndoe, R. A.. (2008). ParaKMeans: Implementation of a parallelized K-means algorithm suitable for general laboratory use. BMC Bioinformatics 9 , pp. 200.

Browning, L. M., Pietrzak, M., Kuczma, M., Simms, C. P., Kurczewska, A., Refugia, J. M., Lowery, D. J., Rempala, G., Gutkin, D., Ignatowicz, L., Muranski, P. and Kraj, P. (2018). Transforming Growth Factor-β mediated enhancement of Th17 cell generation is inhibited by Bone Morphogenetic Receptor 1α signaling. Science Signaling 11 , pp. eaar2125.

Cebula, A., Kuczma, M., Szurek, E., Pietrzak, M., Savage, N., Elhefnawy, W. R.., Rempala, G., Kraj, P. J. and Ignatowicz, L. (2019). Dormant pathogenic CD4(+) T cells are prevalent in the peripheral repertoire of healthy mice. NATURE COMMUNICATIONS 10.

Kuczma, M., Pawlikowska, I., Kopij, M., Podolsky, R., Rempala, G. A.. and Kraj, P. J. (2009). TCR repertoire and Foxp3 expression define functionally distinct subsets of CD4+ regulatory T cells. J Immunol 183 (5) , pp. 3118-29.

Kuczma, M., Podolsky, R., Garge, N., Daniely, D., Pacholczyk, R., Ignatowicz, L. and Kraj, P. J. (2009). Foxp3-deficient regulatory T cells do not revert into conventional effector CD4+ T cells but constitute a unique cell subset. J Immunol 183 (6) , pp. 3731-41.

Pacholczyk, R., Kern, J., Singh, N., Iwashima, M., Kraj, P. J. and Ignatowicz, L. (2007). Nonself-antigens are the cognate specificities of Foxp3+ regulatory T cells. Immunity 27 (3) , pp. 493-504.

Bone Morphogenic Protein Signaling and Melanoma. Current Treatment Options in Oncology.

Kuczma, M. P., Szurek, E. A., Cebula, A., Ngo, V. L., Pietrzak, M., Kraj, P., Denning, T. L. and Ignatowicz, L. (2020). Self and microbiota-derived epitopes induce CD4+ T cell anergy and conversion into CD4+Foxp3+ regulatory cells. Mucosal Immunity.

Browning, L., Miller, C., Kuczma, M., Pietrzak, M., Jing, Y., Rempala, G., Muranski, P., Ignatowicz, L. and Kraj, P. J. (2020). Bone Morphogenic Proteins are immunoregulatory cytokines controlling Foxp3+ Treg cells. Cell Reports.

Mao, R., Liu, H., Yi, B., Purohit, S., Kuczma, M., Kraj, P. J. and She, J. (2019). Cell-based high throughput screening identified a novel compound that promotes regulatory T cells and prevents autoimmune colitis. BIOCHEMICAL PHARMACOLOGY 169.

Dutta, S., Celestine, M. J., Khanal, S., Huddleston, A., Simms, C., Arca, J. F., Mitra, A., Heller, L., Kraj, P. J., Ledizet, M., Anderson, J. F., Neelakanta, G., Holder, A. and Sultana, H. (2017). Coordination of different complexes to copper(II) and cobalt(III) metal centers enhances Zika virus and dengue virus loads in both arthropod cells and human keratinocytes. Biochimica et Biophysica Acta.

Kraj, P. J. and Ignatowicz, L. (2017). The mechanisms shaping the repertoire of CD4+ Foxp3+ Treg cells. Immunology.

Ran, L., Yu, Q., Xiong, F., Cheng, J., Yang, P., Xu, J., Nie, H., Zhang, Q., Yang, X., Yang, F., Gong, Q., Kuczma, M., Kraj, P., Gu, W., Ren, B. and Wang, C. (2015). Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages. Disease Models and Mechanisms 8 , pp. 691-700.

Zhong, J., Yu, Q., Yang, P., Rao, X., He, L., Fang, J., Tu, Y., Zhang, Z., Lai, Q., Zhang, S., Kuczma, M., Kraj, P. J., Xu, J. F.., Gong, F., Zhou, J., Wen, L., Eizirik, D. L.., Du, J., Wang, W. and Wang, C. Y.. (2014). MBD2 regulates TH17 differentiation and experimental autoimmune encephalomyelitis by controlling the homeostasis of T-bet/Hlx axis. J Autoimmun 53 , pp. 95-104.

Yang, P., Zhang, Y., Xu, J., Zhang, S., Yu, Q., Pang, J., Rao, X., Kuczma, M., Marrero, M. B.., Fulton, D., Kraj, P. J., Su, Y. and Wang, C. Y.. (2013). SUMO1 regulates endothelial function by modulating the overall signals in favor of angiogenesis and homeostatic responses. Am J Transl Res 5 (4) , pp. 427-40.

Mao, R., Xiao, W., Liu, H., Chen, B., Yi, B., Kraj, P. J. and She, J. X.. (2013). Systematic evaluation of 640 FDA drugs for their effect on CD4(+)Foxp3(+) regulatory T cells using a novel cell-based high throughput screening assay. Biochem Pharmacol 85 (10) , pp. 1513-24.

Kuczma, M., Kopij, M., Pawlikowska, I., Wang, C. Y.., Rempala, G. A.. and Kraj, P. J. (2010). Intratumoral convergence of the TCR repertoires of effector and Foxp3+ CD4+ T cells. PLoS One 5 (10) , pp. e13623.

Pacholczyk, R., Ignatowicz, H., Kraj, P. J. and Ignatowicz, L. (2006). Origin and T cell receptor diversity of Foxp3+CD4+CD25+ T cells. Immunity 25 (2) , pp. 249-59.

Pacholczyk, R., Kraj, P. J. and Ignatowicz, L. (2002). Peptide specificity of thymic selection of CD4+CD25+ T cells. J Immunol 168 (2) , pp. 613-20.

Sullivan, B. A.., Kraj, P. J., Weber, D. A.., Ignatowicz, L. and Jensen, P. E.. (2002). Positive selection of a Qa-1-restricted T cell receptor with specificity for insulin. Immunity 17 (1) , pp. 95-105.

Chmielowski, B., Pacholczyk, R., Kraj, P. J., Kisielow, P. and Ignatowicz, L. (2002). Presentation of antagonist peptides to naive CD4+ T cells abrogates spatial reorganization of class II MHC peptide complexes on the surface of dendritic cells. Proc Natl Acad Sci U S A 99 (23) , pp. 15012-7.

Kraj, P. J., Pacholczyk, R. and Ignatowicz, L. (2001). Alpha beta TCRs differ in the degree of their specificity for the positively selecting MHC/peptide ligand. J Immunol 166 (4) , pp. 2251-9.

Pacholczyk, R., Kraj, P. J. and Ignatowicz, L. (2001). An incremental increase in the complexity of peptides bound to class II MHC changes the diversity of positively selected alpha beta TCRs. J Immunol 166 (4) , pp. 2357-63.

Gaszewska-Mastalarz, A., Muranski, P., Chmielowski, B., Kraj, P. J. and Ignatowicz, L. (2000). Altered selection of CD4+ T cells by class II MHC bound with dominant and low abundance self-peptides. J Immunol 165 (11) , pp. 6099-106.

Kraj, P. J., Rao, S. P.., Glas, A. M.., Hardy, R. R.., Milner, E. C.. and Silberstein, L. E.. (1997). The human heavy chain Ig V region gene repertoire is biased at all stages of B cell ontogeny, including early pre-B cells. J Immunol 158 (12) , pp. 5824-32.

Kraj, P. J., Friedman, D. F.., Stevenson, F. and Silberstein, L. E.. (1995). Evidence for the overexpression of the VH4-34 (VH4.21) Ig gene segment in the normal adult human peripheral blood B cell repertoire. J Immunol 154 (12) , pp. 6406-20.

Biggs, D. D.., Kraj, P. J., Goldman, J., Jefferies, L., Carchidi, C., Anderson, K. and Silberstein, L. E.. (1995). Immunoglobulin gene sequence analysis to further assess B-cell origin of multiple myeloma. Clin Diagn Lab Immunol 2 (1) , pp. 44-52.

Presentations

Kraj, P. J. (November 9, 2019). Bone Morphogenetic Receptor 1α Signaling Controls Generation of Th17 Effector T Cells and Foxp3+ Regulatory T Cells Oral Presentation Departmental Seminar ¹ÏÉñÍø.

(March 14, 2017). Are gap junctions a connection to therapy of diabetes? Oral Presentation EVMS.

Kraj, P. Jan. (January 16, 2015). Is connexin 43 a pivot regulating T cell differentiation and activation? Oral Presentation Departmental Seminar MGB.

Kraj, P. J. (November 20, 2014). Tumor growth- or aging-mediated evolution of TCR repertoires of effector CD4+ TH cells and Foxp3+ TR cells Oral Presentation Cancer and the Immune System Columbus.

Kraj, P. J. (October 29, 2014). Bone Morphogenic Protein Receptor 1α and its ligands as a signaling circuit promoting immune suppression in tumors Oral Presentation .

• 2004: Research Award, Georgia Cancer Coalition
• 1992: Research Fellowship, The Kosciuszko Foundation