Laboratory of Experimental Medicine

The aim of the projects carried out in the Laboratory of Experimental Medicine is to:

  1. identify and validate novel molecular targets for anti-cancer therapies with the main focus on mechanisms regulating protein homeostasis in mammalian cells (such as ubiquitin-proteasome system, autophagy, endoplasmic reticulum-associated degradation, and unfolded protein response);
  2. study the role on the immune system in the tumor development, progression and sensitivity to anti-cancer treatments and to elucidate novel targets/protocols for the immunotherapy of tumors;
  3. study the role of selected signaling pathways in the development and progression of tumors.

Our research involves studies in primary human cancer cells, established human and mouse cancer cell lines and syngeneic as well as xenograft tumor models in mice. We have developed numerous syngeneic tumor models for the in vivo study of the innate as well as antigen-specific immune responses and focused our attempts to improve multicolor flow cytometry-based immunophenotyping of tumor-infiltrating cells. We use 3D cell cultures as well as invasion and migration assays to better characterize tumor cells and their microenvironment.

We do our best to combine our knowledge in medicine, molecular biology and bioinformatics to discover novel, effective and clinically applicable anti-tumor treatment modalities.

Prof. Dominika Nowis
email: d.nowis@cent.uw.edu.pl
phone: +48 22 55 43720
room: 04.63

 

Degrees: M.D. (2003), Ph.D. (medicine, 2005), D.Sc. (Habilitation, immunology)

Titles: Professor of medicine (2016)

 

Affiliation: Center of New Technologies, University of Warsaw, Poland and Medical University of Warsaw

 

Research Interests:

1) identification and validation of novel molecular targets for anti-cancer therapies with the main focus on the mechanisms regulating protein homeostasis in mammalian cells (such as ubiquitin-proteasome system, autophagy,  endoplasmic reticulum-associated degradation, and unfolded protein response);

2) elucidation of the role on the immune system in the tumor development, progression and sensitivity to anti-cancer treatments and discovery of novel targets/protocols for the immunotherapy of tumors;

3) study the role of selected signaling pathways in the development and progression of tumors.

Education:

2016    Professor of medicine title awarded by the President of the Republic of Poland

2011    Medical University of Warsaw, Poland, I Faculty of Medicine, habilitation (D.Sc.), D.Sc. thesis “Intracellular protein degradation mechanisms and their role in the development of human pathologies”

2005    Medical University of Warsaw, Poland, Center for Biostructure Research, Ph.D., “Potentialisation of photodynamic therapy of cancer in vitro and in vivo”, summa cum laude

2003 – 2004   Clinical internship, Military Institute of Medicine, Warsaw, Poland; unrestricted M.D. licence

1997 – 2003    Medical University of Warsaw, Poland, II Faculty of Medicine, M.D., with honors

 

Positions held:

10.2015 – current, Associate Professor, Genomic Medicine, Medical University of Warsaw, Poland

2014 – current, Professor, head of Laboratory of Experimental Medicine, Centre of New Technologies, University of Warsaw, Poland

02.2014 – 09.2015, Associate Professor, Genomic Medicine, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Poland

2011 – 02.2014, Associate Professor, Department of Immunology, Centre for Biostructure Research, Medical University of Warsaw, Warsaw, Poland

2006 – 2011, Assistant Professor, Department of Immunology, Centre for Biostructure Research, Medical University of Warsaw, Warsaw, Poland

2005 – 2006, Senior Research Assistant, Department of Immunology, Centre for Biostructure Research, Medical University of Warsaw, Warsaw, Poland

1999 – 2005, Student Research Assistant, Department of Immunology, Centre for Biostructure Research, Medical University of Warsaw, Warsaw, Poland

 

Visiting Researcher

09-10.2018 (4 weeks) MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, UK

10.2017 (4 weeks) MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, UK

09-10.2016 (4 weeks) MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, UK

08-09.2013 (4 weeks) Section of Clinical Neurology, Department of Neurological, Neuropsychological, Morphological, and Movement Sciences, University of Verona, Italy

07-08.2009 (4 weeks) UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Ireland

2005 – 2006   Department of Anatomy and Cell Biology, Indiana University School of Medicine-Evansville, Evansville, IN, USA

07-08.2002 (8 weeks) Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

 

Memberships:

UICC (International Union against Cancer) – from 2002

AACR (American Association of Cancer Research) – associate member from 2006, active member from 2014

AACR CIMM (Cancer Immunology Working Group) member from 2016

ASP (American Society for Photobiology) – 2010

Next Generation Haematology (Hematologia Nowej Generacji) – Polish, from 2018

 

Editorships & Reviewing boards:

International Journal of Biochemistry and Cell Biology – editorial board member

Peer reviewing: Journal of Medicinal Chemistry, Neuroscience, Mediators of Inflammation, BMC Cancer, Photochemical & Photobiological Sciences, Photodiagnosis and Photodynamic Therapy, Photochemistry Photobiology, Clinical and Developmental Biology, Biochemistry and Cell Biology, Current Medicinal Chemistry, Central European Journal of Biology, Acta Haematologica Polonica, Cytometry Part A, Medicine, Free Radicals Biology & Medicine, BMC Cardiovascular Disorders

Grant applications reviewing: Foundation for Polish Science, National Science Centre, POLPHARMA Foundation, Collegium Invisibile

 

International scientific collaboration:

  • Gaetano Vattemi, Section of Clinical Neurology, Department of Neurological, Neuropsychological, Morphological, and Movement Sciences, University of Verona, Verona, Italy
  • Dariusz Gorecki, Institute of Biomedical and Biomolecular Sciences, School of Pharmacy and Biomedical Sciences, University of Portsmouth, UK
  • Vincenzo Cerundolo, MRC Human Immunology Unit, Radcliffe Department of Medicine, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
  • Stefano Volinia, LTTA, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy

 

Recent major publications:

  1. Szczałuba K, Chmielewska JJ, Sokolowska O, Rydzanicz M, Szymańska K, Feleszko W, Włodarski P, Biernacka A, Murcia Pienkowski V, Walczak A, Bargeł E, Królewczyk K, Nowacka A, Stawiński P, Nowis D, Dziembowska M, Płoski R. Neurodevelopmental phenotype caused by a de novo PTPN4 point mutation disrupting protein localization in neuronal dendritic spines. Clin Genet. 2018; Sep 21. doi: 10.1111/cge.13450
  2. Chlebowska-Tuz J, Sokolowska O, Gaj P, Lazniewski M, Firczuk M, Borowiec K, Sas-Nowosielska H, Bajor M, Malinowska A, Muchowicz A, Ramji K, Stawinski P, Sobczak M, Pilch Z, Rodziewicz-Lurzynska A, Zajac M, Giannopoulos K, Juszczynski P, Basak GW, Plewczynski D, Ploski R, Golab J*, Nowis D*. Inhibition of protein disulfide isomerase induces differentiation of acute myeloid leukemia cells. Haematologica. 2018 Jul 12. pii: haematol.2018.190231. doi: 10.3324/haematol.2018.190231. PMID: 3000212
  3. Waligora M, Koperny M, Jaeschke RR, Wozniak A, Piasecki J, Sliwka A, Mitus JW, Wasylewski MT, Strzebonska K, Polak M, Nowis D, Fergusson D, Bala MM, Kimmelman J. Risk and Surrogate Benefit for Pediatric Phase 1 Trials in Oncology: A Systematic Review with Meta-analysis. PLoS Med 2018; 15(2): e1002505. https://doi.org/10.1371/journal.pmed.1002505. PMID: 29462168
  4. Sokolowska O, Nowis D. STING signaling in cancer cells – important or not? Archivum Immunologiae et Therapiae Experimentalis 2017 Jul 26; doi: 10.1007/s00005-017-0481-7. PMID: 28748479
  5. Guglielmi V, Voermans NC, Oosterhof A, Nowis D, van Engelen BG, Tomelleri G, Vattemi G.. Evidence of ER stress and UPR activation in patients with Brody disease and Brody syndrome. Neuropathology and Applied Neurobiology 2017; doi: 10.1111/nan.12431. PMID: 28801956
  6. Guglielmi V*, Nowis D*, Tinelli M, Malatesta M, Paoli L, Marini M, Manganotti P, Sadowski R, Wilczynski GM, Meneghini V, Tomelleri G, Vattemi G. Bortezomib-induced muscle toxicity in multiple myeloma. J Neuropathol Exp Neurol 2017 Jul 1;76(7):620-630. doi: 10.1093/jnen/nlx043. PMID: 28863457
  7. Mroczek S, Chlebowska J, Kulinski TM, Cysewski D, Gewartowska O, Liudkovska V, Gruchota J, Borsuk E, Nowis D, Dziembowski A. FAM46C gene encodes a non-canonical poly(A) polymerase acting as a multiple myeloma onco-suppressor. Nat Comm. 2017,8: 619; doi:10.1038/s41467-017-00578-5. PMID: 28931820
  8. Winiarska M, Nowis D, Firczuk M, Zagozdzon A, Gabrysiak M, Barankiewicz J, Sadowski R, Dwojak M, Golab J. Selection of optimal promoter for gene expression in normal B cells. Mol Med Rep. 2017 Jul 14. doi: 10.3892/mmr.2017.6974. PMID: 28713922
  9. Sharma D, al-Khalidi R, Edgar S, An Q, Wang Y, Young C, Nowis D, Gorecki D. Co-delivery of Indoleamine 2,3-dioxygenase prevents loss of expression of an antigenic transgene in dystrophic mouse muscles. Gene Ther. 2017 Feb;24(2):113-119. doi: 10.1038/gt.2016.82; doi: 10.1038/gt.2016.82. PMID: 28004656
  10. Polak A, Kiliszek P, Sewastianik T, Szydlowski M, Jablonska E, Bialopiotrowicz E, Gorniak P, Markowicz S, Nowak E, Grygorowicz MA, Prochorec-Sobieszek M, Nowis D, Golab J, Giebel S, Lech-Maranda E, Warzocha K, Juszczynski P. MEK1 inhibitor, selumetinib, sensitizes precursor B-cell acute lymphoblastic leukemia (B-ALL) cells to dexamethasone through modulation of mTORC1 activity and stimulation of autophagy. PloS One 2016;11(5):e0155893. doi: 10.1371/journal.pone.0155893. PMID: 27196001
  11. Trzeciecka A, Klossowski S, Bajor M, Zagozdzon R, Gaj P, Muchowicz A, Malinowska A, Czerwoniec A, Barankiewicz J, Domagala A, Chlebowska J, Prochorec-Sobieszek M, Winiarska M, Ostaszewski R, Golab J, Nowis D, Firczuk M. Dimeric peroxiredoxins are druggable targets in human Burkitt’s lymphoma cell lines. Oncotarget 2016;7(2):1717-31. doi: 10.18632/oncotarget.6435. PMID: 26636537
  12. Waligora M, Bala MM, Koperny M, Jaeschke RR, Kargul A, Piasecki J, Nowis D, Kimmelman J. Risk and benefits of pediatric phase I trials in oncology, 2004 through 2014: a systematic review. PROSPERO 2015:CRD42015015961.
  13. Mlynarczuk-Bialy I, Doeppner TR, Golab J, Nowis D, Wilczynski G, Parobczak K, Wigand ME, Kwapisiewicz M, Biały LP, Aniolek O, Henklein P, Bähr M, Schmidt M, Kuckelkorn U, Kloetzel PM. Biodistribution and efficacy studies of the proteasome inhibitor BSc2118 in a mouse melanoma model. Translational Oncology. 2014 Oct 24;7(5):570-9. PMID: 25389452
  14. Nowis D*, Malenda A, Furs K, Oleszczak B, Sadowski R, Chlebowska J, Firczuk M, Bujnicki JM, Staruch AD, Zagozdzon R, Glodkowska-Mrowka E, Szablewski L, Golab J. Statins impair glucose uptake in human cells. BMJ Open Diabetes Research and Care. 2014; 2:e000017. PMID: 25452863
  15. O’Leary PC, Terrile M, Bajor M, Gaj P, Hennessy BT, Mills GB, Zagozdzon A, O’Connor DP, Brennan DJ, Connor K, Li J, Gonzalez-Angulo AM, Sun HD, Pu JX, Pontén F, Uhlén M, Jirström K, Nowis D, Crown JP, Zagozdzon R, Gallagher WM. Peroxiredoxin-1 protects estrogen receptor α from oxidative stress-induced suppression and is a protein biomarker of favorable prognosis in breast cancer. Breast Cancer Res. 2014 Jul 10;16(4):R79. PMID: 25011585
  16. Muchowicz A, Firczuk M, Chlebowska J, Nowis D, Stachura J, Barankiewicz J, Trzeciecka A, Kłossowski S, Ostaszewski R, Zagożdżon R, Pu JX, Sun HD, Golab J. Adenanthin targets proteins involved in the regulation of disulphide bonds. Biochem Pharm. 2014;89(2):210-6. PMID: 24630929
  17. Dzięcielewski I, Kamińska A, Sivanesan A, Witkowska E, Golab J, Winiarska M, Nowis D, Weyher JL, Waluk J. Detection of DNA Mutations Using Novel SERS (Surface-Enhanced Raman Spectroscopy) Diagnostic Platform. J. Chem. Chem. Eng. 2013; (7): 972-978.
  18. Firczuk M, Gabrysiak M, Barankiewicz J, Domagala A, Nowis D, Kujawa M, Jankowska-Steifer E, Wachowska M, Glodkowska-Mrowka E, Korsak B, Winiarska M, Golab J. GRP78-targeting subtilase cytotoxin sensitizes cancer cells to photodynamic therapy. Cell Death Dis. 2013;4:e741. PMID: 23887632

 

Teaching experience:

2003- present: Lecturing at the seminars in immunology  (complete course of immunology) for the second-year Polish and English division of medicine, dentistry, pharmacy and clinical diagnostics students

2015-2016: Lecturing at the seminars in pathomorphology for the third-year Polish division of medicine students

Supervisor of 7 defended Ph.D. theses

Awards:

1997 – Award of the Mayor of the City of Warsaw for the best high school graduation

2002 – ICRETT – International Cancer Technology Transfer Fellowship awarded by UICC (International Union against Cancer) for the project entitled: “The role of D-cyclins in tumor development”, supervisor: prof. Peter Sicinski, MD, PhD

2002 – Scholar of the Ministry of Public Health of Poland

2003 – Annual Scientific Award, Medical University of Warsaw

2003 – L’Oreal Poland for Women and Science Ph.D. Award

2004 -National award and grant for young scholars of The Foundation for Polish Science (START)

2005 – Group award of the Ministry of Public Health of Poland for the cycle of 6 publications in experimental oncology

2006 – Individual award of the Rector of The Medical University of Warsaw for the outstanding doctoral thesis and a cycle of review articles in the field of experimental oncology

2008 – „Stay with us” fellowship for young researchers awarded by POLITYKA weekly journal

2008 – 3-year fellowship for Outstanding Young Researchers awarded by the Ministry of Science and Higher Education

2009- ICRETT – International Cancer Technology Transfer Fellowship awarded by UICC (International Union against Cancer) for the project entitled: “Thioredoxin system and anticancer effects of photodynamic therapy”, supervisor: prof. William M. Gallagher

2010 – Group award of the Ministry of Public Health of Poland for a publication in Cardiovascular Research Journal

2011 – Jakub Karol Parnas award for the best experimental publication of the research results in the field of biochemistry or molecular biology conducted solely in Poland – awarded by the Polish Biochemical Society

2011  – Group award of the Rector of the Medical University of Warsaw for the cycle of publications in experimental oncology

2011 – Golden Cuckoo- award of the Rector of the Medical University of Warsaw for the best cited scientific publication in the past 5 years

2012  – Prime Minister of Poland award for the D.Sc. thesis

2013 – Group award of the Rector of the Medical University of Warsaw for the cycle of publications in experimental oncology

2013 – Mentoring Program awarded by the Foundation for Polish Science (Mentor: Prof. Clara Bloomfield, Distinguished University Professor, William G. Pace III Professor of Cancer Research Cancer Scholar and Senior Advisor, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio, USA)

2014 – Academia Net nomination (www.academia-net.org) by the National Science Center in Poland

2015 – group award of the Rector of the Medical University of Warsaw for an experimental publication

2017 – group award of the Rector of the Medical University of Warsaw for an experimental publication

 

Languages:
Polish (native), English (fluent), Russian (basic)

Hobbies:
Photography, travelling, art and design

 


Upregulation of MLK4 promotes migratory and invasive potential of breast cancer cells
Marusiak, A. A., Prelowska, M. K., Mehlich, D., Lazniewski, M., Kaminska, K., Gorczynski, A., ... & Biernat, W. (2018).
Oncogene
STING Signaling in Cancer Cells: Important or Not?
Sokolowska, O. and Nowis, D.
Archivum immunologiae et therapiae experimentalis, pp.1-8.
Risk and Surrogate Benefit for Pediatric Phase 1 Trials in Oncology: A Systematic Review with Meta-analysis
Waligora, M., Bala, M. M., Koperny, M., Wasylewski, M.T., Strzebonska, K., Jaeschke, R.R., Wozniak, A., Piasecki, J., Sliwka, A., Mitus, J. W., Polak, M., Nowis, D., Fergusson, D., Kimmelman, J. (2018).
PLoS medicine, 15(2), e1002505.
Inhibition of protein disulfide isomerase induces differentiation of acute myeloid leukemia cells
Chlebowska-Tuz, J., Sokolowska, O., Gaj, P., Lazniewski, M., Firczuk, M., Borowiec, K., ... & Ramji, K. (2018).
Haematologica, 103(11), 1843-1852.
Evidence of ER stress and UPR activation in patients with Brody disease and Brody syndrome
Guglielmi, V., Voermans, N. C., Oosterhof, A., Nowis, D., Engelen, B. G., Tomelleri, G., & Vattemi, G.
Neuropathology and Applied Neurobiology, 44(5), 533-536.
Bortezomib-Induced Muscle Toxicity in Multiple Myeloma.
Guglielmi, V., Nowis, D., Tinelli, M., Malatesta, M., Paoli, L., Marini, M., Manganotti, P., Sadowski, R., Wilczynski, G.M., Meneghini, V. and Tomelleri, G., 2017.
Journal of Neuropathology & Experimental Neurology, 76(7), pp.620-630.
The non-canonical poly(A) polymerase FAM46Cacts as an onco-suppressor in multiple myeloma
Mroczek, S., Chlebowska, J., Kuliński, T. M., Gewartowska, O., Gruchota, J., Cysewski, D., Liudkovska, V., Borsuk, E., Nowis D. A., Dziembowski, A. (2017).
Nature communications, 8(1), 619.
4-(Methylthio) butyl isothiocyanate inhibits the proliferation of breast cancer cells with different receptor status
Prełowska, M., Kaczyńska, A., & Herman-Antosiewicz, A. (2017).
Pharmacological Reports, 69(5), 1059-1066.
SK053, a small molecule inhibitor of enzymes involved in allosteric disulfide bonds formation, shows potent anti-leukemic effects and induces differentiation of human AML cells.
Nowis, D., Chlebowska, J., Gaj, P., Lazniewski, M., Firczuk, M., Furs, K., Sadowski, R., Leszczynski, P., Stawinski, P., Klossowski, S. and Ostaszewski, R.
(2015): 5347-5347.
MEK1 Inhibitor Selumetinib Sensitizes Precursor B-Cell Acute Lymphoblastic Leukemia Cells (B-ALL) to Dexamethasone through Modulation of mTOR Activity and Stimulation of Autophagy.
Polak, A., Kiliszek, P., Sewastianik, T., Szydłowski, M., Jablońska, E., Białopiotrowicz, E., Górniak, P., Markowicz, S., Nowak, E., Grygorowicz, M. and Nowis, D., 2015.
Hematological Oncology, 33, p.316.
Dimeric peroxiredoxins are druggable targets in human Burkitt lymphoma.
Trzeciecka, A., Klossowski, S., Bajor, M., Zagozdzon, R., Gaj, P., Muchowicz, A., Malinowska, A., Czerwoniec, A., Barankiewicz, J., Domagala, A. and Chlebowska, J., 2016.
Oncotarget, 7(2), p.1717.