Janet Sawicki

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Janet Sawicki
Alma materCornell University (PhD)
University of Delaware (BA)
Scientific career
FieldsCancer nanotherapies, stem cells and cancer, pulmonary Mycobacterium avium
InstitutionsLankenau Institute for Medical Research

Janet Sawicki is an American cancer researcher and the former Deputy Director of the Lankenau Institute for Medical Research (LIMR). Her research is focused on the preclinical development of treatments for cancers, including prostate, ovarian, cervical and pancreatic. She is most notable among cancer biologists for her extensive work on cancer nanotherapies.[1]

Education and career

Sawicki earned her B.A. in Biology from the University of Delaware in 1971.[citation needed] Her PhD in Genetics was earned at Cornell University in 1976.[citation needed]

She trained in classical Drosophila genetics and developmental biology at Cornell and at Yale University as a postdoctoral researcher, and then with Charles Epstein at University of California at San Francisco (UCSF).[2][3][4][5][6] While at UCSF, she expanded her research interests to gene regulation/expression in early mammalian development.[1]

In 1981, Sawicki moved back to the mid-Atlantic area to work at the Wistar Institute in Philadelphia, first as a research associate and then as Assistant Professor. She also served as Assistant Professor of Human Genetics in the Associated Faculty of the University of Pennsylvania’s School of Medicine.[citation needed]

Cancer research

In 1990, Sawicki moved her lab to LIMR, where she and her team are developing new therapeutic strategies for improving the treatment of metastatic cancer.[1] These strategies are based on the delivery of genetic material, specifically DNA and siRNA, exclusively to tumor cells, thus protecting healthy cells from damage. She was among the first to explore the use of non-viral vectors for the in vivo delivery of DNA.[7][8][9]

Nanoparticles and HuR research

To carry the genetic material inside cancer cells, Sawicki and her collaborators use nanoparticles. Sawicki identified therapeutic targets and evaluated the efficacy of many nanoparticle formulations in various cancer mouse models, including for pancreatic cancer,[10][11][12][13][14][15][16] as well as for highly aggressive forms of ovarian cancer for which no effective long-term treatment currently exists.[9][17][18]

Sawicki also collaborates in research to develop and administer therapeutic agents that inhibit HuR, an RNA-binding protein that plays a crucial role in promoting the growth of tumors and the development of acquired drug resistance. These studies have contributed to an understanding of the role that HuR plays in regulating the expression of genes that help pancreatic and ovarian cancer cells survive.[19][19][20]

Stem cells

Sawicki's research also entails identifying stem cells in normal developmental processes and the gene-expression profiles of those cells.[21][21][22][23]

Mouse models

Sawicki also generates transgenic mice.[24][25] Using this technology, she has developed several cancer mouse models useful for her lab’s studies, as well as those of other researchers investigating the role of selected genes in cancer initiation and progression.[25][24]

Mycobacterium avium complex

Sawicki also works on pulmonary Mycobacterium avium complex (MAC) infection, a bacterial pathogen found in water and soil that can have profound effects on pulmonary function of infected patients.[26][27][28] She is collaborating with pulmonologists at the Lankenau Medical Center to identify specific sources of MAC infection in the Philadelphia area, how hormonal status influences contraction of the disease, and what lifestyle measures patients can take to avoid re-exposure to MAC.

Awards

Sawicki's research has been funded by awards from the National Institutes of Health and the United States Department of Defense, as well as from private foundations.[1]

In 2008, she was named a "Woman on the Move" by Main Line Today magazine.[29]

References

  1. ^ a b c d "Janet Sawicki, PhD - LIMR - Researcher Profile". LIMR. 2015-09-21. Retrieved 2016-04-21.
  2. ^ Sawicki, Janet A; MacIntyre, Ross J (1977). "Synthesis of ovarian acid phosphatase-1 in Drosophila melanogaster". Developmental Biology. 60 (1): 1–13. doi:10.1016/0012-1606(77)90106-3. PMID 409635.
  3. ^ Yasbin, Ronald; Sawicki, Janet; MacIntyre, Ross J (1978). "A developmental study of acid phosphatase-1 in Drosophila melanogaster". Developmental Biology. 63 (1): 35–46. doi:10.1016/0012-1606(78)90111-2. PMID 415915.
  4. ^ Sawicki, Janet A; MacIntyre, Ross J (1978). "Localization at the ultrastructural level of maternally derived enzyme and determination of the time of paternal gene expression for acid phosphatase-1 in Drosophila melanogaster". Developmental Biology. 63 (1): 47–58. doi:10.1016/0012-1606(78)90112-4. PMID 204531.
  5. ^ Sawicki, Janet A; Magnuson, Terry; Epstein, Charles J (1981). "Evidence for expression of the paternal genome in the two-cell mouse embryo". Nature. 294 (5840): 450–1. doi:10.1038/294450a0. PMID 6171732.
  6. ^ Epstein, C. J; Smith, S. A; Zamora, T; Sawicki, J. A; Magnuson, T. R; Cox, D. R (1982). "Production of viable adult trisomy 17 reversible diploid mouse chimeras". Proceedings of the National Academy of Sciences. 79 (14): 4376–80. doi:10.1073/pnas.79.14.4376. PMC 346674. PMID 6956868.
  7. ^ Peng, Weidan; Anderson, Daniel G; Bao, Yunhua; Padera, Robert F; Langer, Robert; Sawicki, Janet A (2007). "Nanoparticulate delivery of suicide DNA to murine prostate and prostate tumors". The Prostate. 67 (8): 855–62. doi:10.1002/pros.20576. PMID 17427200.
  8. ^ Sawicki, Janet A; Anderson, Daniel G; Langer, Robert (2008). "Nanoparticle Delivery of Suicide DNA for Epithelial Ovarian Cancer Therapy". Ovarian Cancer. Advances in Experimental Medicine and Biology. Vol. 622. pp. 209–19. doi:10.1007/978-0-387-68969-2_17. ISBN 978-0-387-68966-1. PMID 18546630.
  9. ^ a b Huang, Y.-H; Zugates, G. T; Peng, W; Holtz, D; Dunton, C; Green, J. J; Hossain, N; Chernick, M. R; Padera, R. F; Langer, R; Anderson, D. G; Sawicki, J. A (2009). "Nanoparticle-Delivered Suicide Gene Therapy Effectively Reduces Ovarian Tumor Burden in Mice". Cancer Research. 69 (15): 6184–91. doi:10.1158/0008-5472.CAN-09-0061. PMC 2735403. PMID 19643734.
  10. ^ Showalter, S. L; Huang, Y. H; Witkiewicz, A; Costantino, C. L; Yeo, C. J; Green, J. J; Langer, R; Anderson, D. G; Sawicki, J. A; Brody, J. R (2008). "Nanoparticulate delivery of diphtheria toxin DNA effectively kills Mesothelin expressing pancreatic cancer cells". Cancer biology & therapy. 7 (10): 1584–90. PMC 3218426. PMID 19039293.
  11. ^ Tholey, Renee; Sawicki, Janet A; Brody, Jonathan R (2012). "Molecular-Based and Alternative Therapies for Pancreatic Cancer". The Cancer Journal. 18 (6): 665–73. doi:10.1097/PPO.0b013e3182793ff6. PMID 23187855.
  12. ^ Burkhart, Richard A; Peng, Yu; Norris, Zoë A; Tholey, Renée M; Talbott, Vanessa A; Liang, Qin; Ai, Yongxing; Miller, Kathy; Lal, Shruti; Cozzitorto, Joseph A; Witkiewicz, Agnieska K; Yeo, Charles J; Gehrmann, Matthew; Napper, Andrew; Winter, Jordan M; Sawicki, Janet A; Zhuang, Zhihao; Brody, Jonathan R (2013). "Mitoxantrone Targets Human Ubiquitin-Specific Peptidase 11 (USP11) and is a Potent Inhibitor of Pancreatic Cancer Cell Survival". Molecular Cancer Research. 11 (8): 901–11. doi:10.1158/1541-7786.MCR-12-0699. PMID 23696131.
  13. ^ Lal, S; Burkhart, R. A; Beeharry, N; Bhattacharjee, V; Londin, E. R; Cozzitorto, J. A; Romeo, C; Jimbo, M; Norris, Z. A; Yeo, C. J; Sawicki, J. A; Winter, J. M; Rigoutsos, I; Yen, T. J; Brody, J. R (2014). "HuR Posttranscriptionally Regulates WEE1: Implications for the DNA Damage Response in Pancreatic Cancer Cells". Cancer Research. 74 (4): 1128–40. doi:10.1158/0008-5472.CAN-13-1915. PMC 4353573. PMID 24536047.
  14. ^ Tholey, Renee M; Lal, Shruti; Jimbo, Masaya; Burkhart, Richard A; Blanco, Fernando F; Cozzitorto, Joseph A; Eisenberg, Josh D; Jiang, Wei; Iacobuzio-Donahue, Christine A; Witkiewicz, Agnieszka K; Glbert, Melissa; Yeo, Charles J; Brody, Jonathan R; Sawicki, Janet A; Winter, Jordan M (2015). "MUC1 Promoter–Driven DTA as a Targeted Therapeutic Strategy against Pancreatic Cancer". Molecular Cancer Research. 13 (3): 439–48. doi:10.1158/1541-7786.MCR-14-0199. PMID 25336517.
  15. ^ Jimbo, Masaya; Blanco, Fernando F; Huang, Yu-Hung; Telonis, Aristeidis G; Screnci, Brad A; Cosma, Gabriela L; Alexeev, Vitali; Gonye, Gregory E; Yeo, Charles J; Sawicki, Janet A; Winter, Jordan M; Brody, Jonathan R (2015). "Targeting the mRNA-binding protein HuR impairs malignant characteristics of pancreatic ductal adenocarcinoma cells". Oncotarget. 6 (29): 27312–31. doi:10.18632/oncotarget.4743. PMC 4694992. PMID 26314962.
  16. ^ Blanco, F F; Jimbo, M; Wulfkuhle, J; Gallagher, I; Deng, J; Enyenihi, L; Meisner-Kober, N; Londin, E; Rigoutsos, I; Sawicki, J A; Risbud, M V; Witkiewicz, A K; McCue, P A; Jiang, W; Rui, H; Yeo, C J; Petricoin, E; Winter, J M; Brody, J R (2015). "The mRNA-binding protein HuR promotes hypoxia-induced chemoresistance through posttranscriptional regulation of the proto-oncogene PIM1 in pancreatic cancer cells". Oncogene. 35 (19): 2529–41. doi:10.1038/onc.2015.325. PMID 26387536.
  17. ^ Huang, Y.-H; Bao, Y; Peng, W; Goldberg, M; Love, K; Bumcrot, D. A; Cole, G; Langer, R; Anderson, D. G; Sawicki, J. A (2009). "Claudin-3 gene silencing with siRNA suppresses ovarian tumor growth and metastasis". Proceedings of the National Academy of Sciences. 106 (9): 3426–30. doi:10.1073/pnas.0813348106. PMC 2651300. PMID 19208807.
  18. ^ Huang, Yu-Hung; Peng, Weidan; Furuuchi, Narumi; Gerhart, Jacquelyn; Rhodes, Kelly; Mukherjee, Neelanjan; Jimbo, Masaya; Gonye, Gregory E; Brody, Jonathan R; Getts, Robert C; Sawicki, Janet A (2016). "Delivery of Therapeutics Targeting the mRNA-Binding Protein HuR Using 3DNA Nanocarriers Suppresses Ovarian Tumor Growth". Cancer Research. 76 (6): 1549–59. doi:10.1158/0008-5472.CAN-15-2073. PMID 26921342.
  19. ^ a b Huang, Yu-Hung; Cozzitorto, Joseph A; Richards, Nathan G; Eltoukhy, Ahmed A; Yeo, Charles J; Langer, Robert; Anderson, Daniel G; Brody, Jonathan R; Sawicki, Janet A (2014). "CanScript, an 18-Base pair DNA sequence, boosts tumor cell-specific promoter activity". Cancer Biology & Therapy. 10 (9): 878–84. doi:10.4161/cbt.10.9.13234. PMC 3040857. PMID 20798601.
  20. ^ Peng, Weidan; Furuuchi, Narumi; Aslanukova, Ludmila; Huang, Yu-Hung; Brown, Samantha Z; Jiang, Wei; Addya, Sankar; Vishwakarma, Vikalp; Peters, Erika; Brody, Jonathan R; Dixon, Dan A; Sawicki, Janet A (2018). "Elevated HuR in Pancreas Promotes a Pancreatitis-Like Inflammatory Microenvironment That Facilitates Tumor Development". Molecular and Cellular Biology. 38 (3). doi:10.1128/MCB.00427-17. PMC 5770537. PMID 29133460.
  21. ^ a b Huang, Yu-Hung; Peng, Weidan; Furuuchi, Narumi; Duhadaway, James B; Jimbo, Masaya; Pirritano, Andrea; Dunton, Charles J; Daum, Gary S; Leiby, Benjamin E; Brody, Jonathan R; Sawicki, Janet A (2016). "Insights from HuR biology point to potential improvement for second-line ovarian cancer therapy". Oncotarget. 7 (16): 21812–24. doi:10.18632/oncotarget.7840. PMC 5008325. PMID 26943573.
  22. ^ Sawicki, Janet A; Rothman, Craig J (2002). "Evidence for stem cells in cultures of mouse prostate epithelial cells". The Prostate. 50 (1): 46–53. doi:10.1002/pros.10031. PMID 11757035.
  23. ^ Sawicki, J. A (2008). "Fetal Microchimerism and Cancer". Cancer Research. 68 (23): 9567–9. doi:10.1158/0008-5472.CAN-08-3008. PMC 2638004. PMID 19047129.
  24. ^ a b Guo, Yongjun; Zhao, Jiuqiao; Sawicki, Janet; Soler, Alejandro Peralta; O'Brien, Thomas G (1999). "Conversion of C57Bl/6 mice from a tumor promotion-resistant to a -sensitive phenotype by enhanced ornithine decarboxylase expression". Molecular Carcinogenesis. 26 (1): 32–6. doi:10.1002/(SICI)1098-2744(199909)26:1<32::AID-MC4>3.0.CO;2-E. PMID 10487519.
  25. ^ a b Chen, Yan; Megosh, Louis C; Gilmour, Susan K; Sawicki, Janet A; o'Brien, Thomas G (2000). "K6/ODC transgenic mice as a sensitive model for carcinogen identification". Toxicology Letters. 116 (1–2): 27–35. doi:10.1016/s0378-4274(00)00196-x. PMID 10906419.
  26. ^ Lande, Leah; Peterson, Donald D; Gogoi, Radhika; Daum, Gary; Stampler, Kate; Kwait, Rebecca; Yankowski, Christine; Hauler, Kate; Danley, Joshua; Sawicki, Kristen; Sawicki, Janet (2012). "Association Between Pulmonary Mycobacterium Avium Complex Infection and Lung Cancer". Journal of Thoracic Oncology. 7 (9): 1345–51. doi:10.1097/JTO.0b013e31825abd49. PMID 22699888.
  27. ^ Wallace, R. J; Iakhiaeva, E; Williams, M. D; Brown-Elliott, B. A; Vasireddy, S; Vasireddy, R; Lande, L; Peterson, D. D; Sawicki, J; Kwait, R; Tichenor, W. S; Turenne, C; Falkinham, J. O (2013). "Absence of Mycobacterium intracellulare and Presence of Mycobacterium chimaera in Household Water and Biofilm Samples of Patients in the United States with Mycobacterium avium Complex Respiratory Disease". Journal of Clinical Microbiology. 51 (6): 1747–52. doi:10.1128/JCM.00186-13. PMC 3716115. PMID 23536397.
  28. ^ Danley, Joshua; Kwait, Rebecca; Peterson, Donald D; Sendecki, Jocelyn; Vaughn, Beverly; Nakisbendi, Kara; Sawicki, Janet; Lande, Leah (2014). "Normal Estrogen, but Low Dehydroepiandrosterone Levels, in Women with Pulmonary Mycobacterium avium Complex. A Preliminary Study". Annals of the American Thoracic Society. 11 (6): 908–14. doi:10.1513/AnnalsATS.201312-422OC. PMID 24963545.
  29. ^ "Women on the Move - Main Line Today - October 2008 - Philadelphia, PA". Main Line Today. Retrieved 2016-04-21.

External links

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