Pediatric Research

Jeffrey J. Bednarski, M.D., Ph.D. bednarski_j@wustl.edu

Assistant Professor of Pediatrics, Hematology and Oncology

Developmental Biology Hematology and Oncology

phone: (314) 454-6018

Research Interests

Dr. Bednarski's research centers on the development of the immune system. During lymphocyte differentiation, the rearrangement of the antigen receptor genes is essential to ensure a diverse and function immune response. This process requires the intentional generation of breaks in DNA at specific locations in the genes. These breaks are subsequently repaired with removal of some DNA and joining of the remaining segments. The DNA breaks pose an extreme risk to the developing cells. Mis-repair can lead to cell death or to translocations that can result in leukemias and lymphomas. Therefore, it is critical that the breaks be carefully managed by cellular processes that ensure proper repair and maintenance of genomic integrity. Dr. Bednarski's research focuses on how the signals from this DNA damage cooperate with other developmental processes to direct lymphocyte differentiation and survival. His overall goals are to understand the signals important for lymphocyte development and how these signals may be corrupted and thus contribute to the generation of leukemia and lymphoma.

Education

BS, Summa Cum Laude, Duke University, 1995
PhD, University of Michigan, 2003
MD, Graduation with Distinction in Research, University of Michigan, 2003

Training

Postdoctoral Fellow in Pediatric Hematology-Oncology, Boston Children's Hospital, 2003 - 2003
Resident in Pediatrics, St. Louis Children's Hospital, 2003 - 2006
Clinical Fellow in Pediatric Hematology-Oncology, Washington University School of Medicine, 2006 - 2009
Postdoctoral Fellow in Immunology, Washington University School of Medicine, 2007 - 2013

Licensure and Board Certification

American Board of Pediatrics, Board Certified , 2006
MO, Medical License , 2009
Pediatric Hematology-Oncology, Board Certified , 2011

Honors

Phi Eta Sigma, National Freshman Honor Society, 1992
Golden Key National Honor Society, 1993
National Institute of General Medicine Summer Scholar, 1993
Phi Beta Kappa, 1994
Phi Lambda Upsilon, National Honorary Chemical Society, 1994
Summa cum laude graduate, Duke University, 1995
Regent's Fellowship, University of Michigan Rackham Graduate School, 1997 - 2001
Graduation with Distinction in Research, University of Michigan Medical School, 2003
James P. Keating Ouststanding Resident Award, St. Louis Children's Hospital, 2005
David Gilstrap Memorial Award, St. Louis Children's Hospital, 2008
Hyundai Hope on Wheels Scholar, 2012 - 2013
Hyundai Hope on Wheels Scholar, 2012 - 2013

Selected Publications view all (20)

Publication Co-Authors

Mary C. Dinauer, M.D., Ph.D.

Avraham Beigelman, M.D.

1.	Koues OI, Kowalewski RA, Chang LW, Pyfrom SC, Schmidt JA, Luo H, Sandoval LE, Hughes TB, Bednarski JJ, Cashen AF, Payton JE, Oltz EM. Enhancer sequence variants and transcription-factor deregulation synergize to construct pathogenic regulatory circuits in B-cell lymphoma. Immunity. 2015;42(1):186-98. doi:10.1016/j.immuni.2014.12.021 PMCID:PMC4302272 PMID:25607463
2.	Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Pai SY, Ballard B, Bauer SC, Bleesing JJ, Boyle M, Brower A, Buckley RH, van der Burg M, Burroughs LM, Candotti F, Cant AJ, Chatila T, Cunningham-Rundles C, Dinauer MC, Dvorak CC, Filipovich AH, Fleisher TA, Bobby Gaspar H, Gungor T, Haddad E, Hovermale E, Huang F, Hurley A, Hurley M, Iyengar S, Kang EM, Logan BR, Long-Boyle JR, Malech HL, McGhee SA, Modell F, Modell V, Ochs HD, O'Reilly RJ, Parkman R, Rawlings DJ, Routes JM, Shearer WT, Small TN, Smith H, Sullivan KE, Szabolcs P, Thrasher A, Torgerson TR, Veys P, Weinberg K, Zuniga-Pflucker JC, workshop participants. Primary Immune Deficiency Treatment Consortium (PIDTC) report. J Allergy Clin Immunol. 2014;133(2):335-47. doi:10.1016/j.jaci.2013.07.052 PMCID:PMC3960312 PMID:24139498
3.	Steinel NC, Lee BS, Tubbs AT, Bednarski JJ, Schulte E, Yang-Iott KS, Schatz DG, Sleckman BP, Bassing CH. The ataxia telangiectasia mutated kinase controls Igκ allelic exclusion by inhibiting secondary Vκ-to-Jκ rearrangements. J Exp Med. 2013;210(2):233-9. doi:10.1084/jem.20121605 PMCID:PMC3570110 PMID:23382544
4.	Bednarski JJ, Sleckman BP. Integrated signaling in developing lymphocytes: the role of DNA damage responses. Cell Cycle. 2012;11(22):4129-34. doi:10.4161/cc.22021 PMCID:PMC3524208 PMID:23032308
5.	Bednarski JJ, Nickless A, Bhattacharya D, Amin RH, Schlissel MS, Sleckman BP. RAG-induced DNA double-strand breaks signal through Pim2 to promote pre-B cell survival and limit proliferation. J Exp Med. 2012;209(1):11-7. doi:10.1084/jem.20112078 PMCID:PMC3260864 PMID:22201128
6.	Bednarski JJ, Sleckman BP. Lymphocyte development: integration of DNA damage response signaling. Adv Immunol. 2012;116:175-204. doi:10.1016/B978-0-12-394300-2.00006-5 PMID:23063077
7.	Gapud EJ, Dorsett Y, Yin B, Callen E, Bredemeyer A, Mahowald GK, Omi KQ, Walker LM, Bednarski JJ, McKinnon PJ, Bassing CH, Nussenzweig A, Sleckman BP. Ataxia telangiectasia mutated (Atm) and DNA-PKcs kinases have overlapping activities during chromosomal signal joint formation. Proc Natl Acad Sci U S A. 2011;108(5):2022-7. doi:10.1073/pnas.1013295108 PMCID:PMC3033293 PMID:21245316
8.	Helmink BA, Tubbs AT, Dorsett Y, Bednarski JJ, Walker LM, Feng Z, Sharma GG, McKinnon PJ, Zhang J, Bassing CH, Sleckman BP. H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytes. Nature. 2011;469(7329):245-9. doi:10.1038/nature09585 PMCID:PMC3150591 PMID:21160476
9.	Helmink BA, Bredemeyer AL, Lee BS, Huang CY, Sharma GG, Walker LM, Bednarski JJ, Lee WL, Pandita TK, Bassing CH, Sleckman BP. MRN complex function in the repair of chromosomal Rag-mediated DNA double-strand breaks. J Exp Med. 2009;206(3):669-79. doi:10.1084/jem.20081326 PMCID:PMC2699138 PMID:19221393
10.	Bednarski JJ, Lyssiotis CA, Roush R, Boitano AE, Glick GD, Opipari AW Jr. A novel benzodiazepine increases the sensitivity of B cells to receptor stimulation with synergistic effects on calcium signaling and apoptosis. J Biol Chem. 2004;279(28):29615-21. doi:10.1074/jbc.M403507200 PMID:15123639

1.	Zafar R, Ver Heul A, Beigelman A, Bednarski JJ, Bayliss SJ, Dehner LP, Rosman IS, Coughlin CC. Omenn Syndrome Presenting with Striking Erythroderma and Extreme Lymphocytosis in a Newborn. Pediatr Dermatol. 2017;34(1):e37-e39. PMID:27862277
2.	Bednarski JJ, Pandey R, Schulte E, White LS, Chen BR, Sandoval GJ, Kohyama M, Haldar M, Nickless A, Trott A, Cheng G, Murphy KM, Bassing CH, Payton JE, Sleckman BP. RAG-mediated DNA double-strand breaks activate a cell type-specific checkpoint to inhibit pre-B cell receptor signals. J Exp Med. 2016;213(2):209-23. PMCID:PMC4749927 PMID:26834154
3.	Franco M, Panas MW, Marino ND, Lee MC, Buchholz KR, Kelly FD, Bednarski JJ, Sleckman BP, Pourmand N, Boothroyd JC. A Novel Secreted Protein, MYR1, Is Central to Toxoplasma's Manipulation of Host Cells. MBio. 2016;7(1):e02231-15. PMCID:PMC4742717 PMID:26838724
4.	Liu C, Duffy B, Bednarski JJ, Calhoun C, Lay L, Rundblad B, Payton JE, Mohanakumar T. Maternal T-Cell Engraftment Interferes With Human Leukocyte Antigen Typing in Severe Combined Immunodeficiency. Am J Clin Pathol. 2016;145(2):251-7. PMCID:PMC4901308 PMID:26834123
5.	Bednarski JJ. DNA damage signals inhibit neutrophil function. Blood. 2015;126(26):2773-4. PMCID:PMC4692138 PMID:26705340
6.	Koues OI, Kowalewski RA, Chang LW, Pyfrom SC, Schmidt JA, Luo H, Sandoval LE, Hughes TB, Bednarski JJ, Cashen AF, Payton JE, Oltz EM. Enhancer sequence variants and transcription-factor deregulation synergize to construct pathogenic regulatory circuits in B-cell lymphoma. Immunity. 2015;42(1):186-98. doi:10.1016/j.immuni.2014.12.021 PMCID:PMC4302272 PMID:25607463
7.	Griffith LM, Cowan MJ, Notarangelo LD, Kohn DB, Puck JM, Pai SY, Ballard B, Bauer SC, Bleesing JJ, Boyle M, Brower A, Buckley RH, van der Burg M, Burroughs LM, Candotti F, Cant AJ, Chatila T, Cunningham-Rundles C, Dinauer MC, Dvorak CC, Filipovich AH, Fleisher TA, Bobby Gaspar H, Gungor T, Haddad E, Hovermale E, Huang F, Hurley A, Hurley M, Iyengar S, Kang EM, Logan BR, Long-Boyle JR, Malech HL, McGhee SA, Modell F, Modell V, Ochs HD, O'Reilly RJ, Parkman R, Rawlings DJ, Routes JM, Shearer WT, Small TN, Smith H, Sullivan KE, Szabolcs P, Thrasher A, Torgerson TR, Veys P, Weinberg K, Zuniga-Pflucker JC, workshop participants. Primary Immune Deficiency Treatment Consortium (PIDTC) report. J Allergy Clin Immunol. 2014;133(2):335-47. doi:10.1016/j.jaci.2013.07.052 PMCID:PMC3960312 PMID:24139498
8.	Steinel NC, Lee BS, Tubbs AT, Bednarski JJ, Schulte E, Yang-Iott KS, Schatz DG, Sleckman BP, Bassing CH. The ataxia telangiectasia mutated kinase controls Igκ allelic exclusion by inhibiting secondary Vκ-to-Jκ rearrangements. J Exp Med. 2013;210(2):233-9. doi:10.1084/jem.20121605 PMCID:PMC3570110 PMID:23382544
9.	Bednarski JJ, Sleckman BP. Integrated signaling in developing lymphocytes: the role of DNA damage responses. Cell Cycle. 2012;11(22):4129-34. doi:10.4161/cc.22021 PMCID:PMC3524208 PMID:23032308
10.	Bednarski JJ, Nickless A, Bhattacharya D, Amin RH, Schlissel MS, Sleckman BP. RAG-induced DNA double-strand breaks signal through Pim2 to promote pre-B cell survival and limit proliferation. J Exp Med. 2012;209(1):11-7. doi:10.1084/jem.20112078 PMCID:PMC3260864 PMID:22201128
11.	Bednarski JJ, Sleckman BP. Lymphocyte development: integration of DNA damage response signaling. Adv Immunol. 2012;116:175-204. doi:10.1016/B978-0-12-394300-2.00006-5 PMID:23063077
12.	Gapud EJ, Dorsett Y, Yin B, Callen E, Bredemeyer A, Mahowald GK, Omi KQ, Walker LM, Bednarski JJ, McKinnon PJ, Bassing CH, Nussenzweig A, Sleckman BP. Ataxia telangiectasia mutated (Atm) and DNA-PKcs kinases have overlapping activities during chromosomal signal joint formation. Proc Natl Acad Sci U S A. 2011;108(5):2022-7. doi:10.1073/pnas.1013295108 PMCID:PMC3033293 PMID:21245316
13.	Helmink BA, Tubbs AT, Dorsett Y, Bednarski JJ, Walker LM, Feng Z, Sharma GG, McKinnon PJ, Zhang J, Bassing CH, Sleckman BP. H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytes. Nature. 2011;469(7329):245-9. doi:10.1038/nature09585 PMCID:PMC3150591 PMID:21160476
14.	Helmink BA, Bredemeyer AL, Lee BS, Huang CY, Sharma GG, Walker LM, Bednarski JJ, Lee WL, Pandita TK, Bassing CH, Sleckman BP. MRN complex function in the repair of chromosomal Rag-mediated DNA double-strand breaks. J Exp Med. 2009;206(3):669-79. doi:10.1084/jem.20081326 PMCID:PMC2699138 PMID:19221393
15.	Bednarski JJ, Lyssiotis CA, Roush R, Boitano AE, Glick GD, Opipari AW Jr. A novel benzodiazepine increases the sensitivity of B cells to receptor stimulation with synergistic effects on calcium signaling and apoptosis. J Biol Chem. 2004;279(28):29615-21. doi:10.1074/jbc.M403507200 PMID:15123639
16.	Bednarski JJ, Warner RE, Rao T, Leonetti F, Yung R, Richardson BC, Johnson KJ, Ellman JA, Opipari AW Jr, Glick GD. Attenuation of autoimmune disease in Fas-deficient mice by treatment with a cytotoxic benzodiazepine. Arthritis Rheum. 2003;48(3):757-66. doi:10.1002/art.10968 PMID:12632430
17.	Fleming JC, Tartaglini E, Kawatsuji R, Yao D, Fujiwara Y, Bednarski JJ, Fleming MD, Neufeld EJ. Male infertility and thiamine-dependent erythroid hypoplasia in mice lacking thiamine transporter Slc19a2. Mol Genet Metab. 2003;80(1-2):234-41. PMID:14567973
18.	Blatt NB, Bednarski JJ, Warner RE, Leonetti F, Johnson KM, Boitano A, Yung R, Richardson BC, Johnson KJ, Ellman JA, Opipari AW Jr, Glick GD. Benzodiazepine-induced superoxide signals B cell apoptosis: mechanistic insight and potential therapeutic utility. J Clin Invest. 2002;110(8):1123-32. doi:10.1172/JCI16029 PMCID:PMC150800 PMID:12393848
19.	Chung SH, Song WJ, Kim K, Bednarski JJ, Chen J, Prestwich GD, Holz RW. The C2 domains of Rabphilin3A specifically bind phosphatidylinositol 4,5-bisphosphate containing vesicles in a Ca2+-dependent manner. In vitro characteristics and possible significance. J Biol Chem. 1998;273(17):10240-8. PMID:9553075
20.	Clementz T, Bednarski JJ, Raetz CR. Function of the htrB high temperature requirement gene of Escherichia coli in the acylation of lipid A: HtrB catalyzed incorporation of laurate. J Biol Chem. 1996;271(20):12095-102. PMID:8662613