Professor Marija Krstic-Demonacos

Professor of Molecular Medicine, Director of Biomedical Research Centre

Office Times

Tuesday and Wednesday 9:00am - 10:00am

Biography

I took up my Chair in Molecular Medicine in the School of Environment & Life Sciences in April 2013 and a post of Director of Biomedical Centre in 2014. Prior to this I was a Wellcome Trust Fellow and Lecturer at the University of Manchester from 2003.  I completed my PhD in molecular endocrinology at the University of California San Francisco and postdoctoral studies in cancer biology at the University of Glasgow. 

I have published more than 50 papers in reputed journals and am serving as an editorial board member of several international journals. In addition, commercialisation potential of my research is evidenced by the three patents I own. I have presented at numerous conferences and served as reviewer for many international funding bodies and journals.

Teaching

Since starting in the University of Salford, I have developed MSc Biomedical Science taught course with five 30 credit modules. I have shaped the course from the start and I am the programme leader as well as module leader for the Cellular basis of disease module. Other teaching activities include delivery of lectures as part of the Cell Biology and Genomics and Proteomics courses. I have also taught tutorial groups across all levels. In addition, I have been supervising summer, placement, final year project and PGR students.

In the University of Manchester, I have delivered lectures for the Genome regulation course. In addition, I have taught tutorial groups from various degrees including Molecular Biology, Biochemistry and Biology. In addition, I have also been a problem based learning tutor for medical students, (12 students), including personal tutoring and pastoral care. I have been invited lecturer for the University of Belgrade that was part of a brain gain programme funded by Austrian government (2007-9).

Research Interests

My research focuses on the investigation of how cells respond to stress. In particular, my research group investigates molecular basis of cellular response to hormonal and stress signals, important for inflammation, cancer, stem cell biology and development.  We analyse of the function of steroid receptors focusing on glucocorticoid hormones (GCs) which are essential for life and among the most extensively prescribed drugs in clinical practice for wide range of conditions including asthma, eczema, arthritis, allergies, in transplantation and for childhood leukaemia treatment.

Glucocorticoids regulate the metabolism of carbohydrates, proteins and lipids, the inflammatory and immune responses, and the hypothalamic-pituitary-adrenal axis. We aim to understand the molecular mechanisms by which these hormones regulate cellular metabolism and exert their effects. My long term interests are in investigating the mechanisms by which these clinically relevant drugs mediate their therapeutic effects in order to improve available treatments and to develop novel pharmacologically beneficial approaches.

We also study effects of DNA damage on tumour suppressor p53 that is a gene mutated in over half of human cancers. The deregulation of DNA damage inducible signalling pathways plays a major role in the development of cancer and analysis of components of these pathways is vital for the diagnosis, prognosis and therapy of malignant tumours. Finally, my group focuses on pathway modelling and genome wide studies as a tool to understand the mechanisms of cellular signalling and to discover new therapeutic targets. These logical models are increasingly predictive and have potential use in personalized medicine.

Overall my observations provide detailed insight in the molecular networks governing cellular survival in numerous physiological and pathological processes. This knowledge can find application in the pharmaceutical industry, has been highly cited and internationally recognized. Several collaborative projects with clinical partners are ongoing in order to translate this knowledge to clinic and to pursue goals of personalized medicine to generate an efficient roadmap that will lead rapidly and safely to effective individual treatment.

Qualifications and Memberships

Qualifications:

1995: PhD in Endocrinology, Department of Biochemistry, University of California San Francisco, San Francisco, California, USA

1987: MSc in Molecular Biology and Biochemistry, Faculty of Natural Sciences, University of Belgrade, Belgrade. Serbia

1984: BSc in Molecular Biology and Physiology, Faculty of Natural Sciences, University of Belgrade, Belgrade, Serbia

Membership:

Endocrine Society (USA), full member since 2011

Society of Biology, full member since 2010

British Association for Cancer Research, full member since 2009

British Endocrine Society, full member since 2008

Biochemical Society, full member since 2007

Publications

1. Qattan, MY, Bakker, EY, Rajendran, R, Wei-Chen Chen, D, Saha, V, Liu, J, Schwartz, J, Mutti, L, Demonacos, C and Krstic- Demonacos, M 2017, Differential regulation of cell death pathways by the microenvironment correlates with chemoresistance and survival in leukaemia , PLoS ONE . (In Press)

2. Guazzelli A, Bakker E, Krstic-Demonacos M, Lisanti MP, Sotgia F, Mutti L., Anti-CTLA-4 therapy for malignant mesothelioma, Immunotherapy. 2017 Mar;9(3):273-280.

3. Kuroda K, Fukuda T, Krstic-Demonacos M, Demonacos C, Okumura K, Isogai H, Hayashi M, Saito K, Isogai E., miR-663a regulates growth of colon cancer cells, after administration of antimicrobial peptides, by targeting CXCR4-p21 pathway., BMC Cancer. 2017 Jan 7;17(1):33.

4. Paolicchi E, Gemignani F, Krstic-Demonacos M, Dedhar S, Mutti L, Landi S., Targeting hypoxic response for cancer therapy, Oncotarget. 2016 Mar 22;7(12):13464-78. doi: 10.18632/oncotarget.7229.

5. Fiorillo M, Lamb R, Tanowitz H, Mutti L, Krstic-Demonacos M, Cappello AR,  Martinez-Outschoorn U, Lisanti M, Repurposing Atovaquone: Targeting mitochondrial complex III and OXPHOS to eradicate cancer stem cells, Oncotarget. 2016 Jun 7;7(23):34084-99.

6. Al-Sudani, B, Krstic- Demonacos, M and Ragazzon, PA 2015, Novel therapies for cancer treatment: Designing high affinity and selectivity ligands against SIRT1 , in: EuroMedLab Paris 2015, 21-25 June 2015, Paris, France.

7. Guazzelli A, Hussain M, Krstic-Demonacos M, Mutti L, Tremelimumab for the treatment of malignant mesothelioma,  Expert Opin Biol Ther. 2015 Dec;15(12):1819-29.

8. Bakker E, Qattan M, Mutti L, Demonacos C, Krstic-Demonacos M, The role of microenvironment and immunity in drug response in leukemia, Biochim Biophys Acta. 2016 Mar;1863(3):414-26.

9. Hussain M, Tian K,  Mutti L, Krstic-Demonacos M,  Schwartz JM,  The Expanded p53 Interactome as a Predictive Model for Cancer Therapy, GCB, Vol. 1, No. 1 (2015): e20

10. Kuroda K, Fukuda T, Isogai H, Okumura K, Krstic-Demonacos M, Isogai E, Antimicrobial peptide FF/CAP18 induces apoptotic cell death in HCT116 colon cancer cells via changes in the metabolic profile, Int J Oncol. 2015 Apr;46(4):1516-26

11. Hussain, M, Stutchbury, B & Tian, K, Atalay, R, Schwartz, JM, Demonacos, MK 2014, Applications of p53 Interactome Analysis to Personalised Drug Discovery, in: 'Proceedings IWBBIO 2014', Universidad de Granada, Granada, Spain, pp.192-203. Conference details: Granada 7-9 April, 2014.

12. Leung T, Rajendran R, Singh S, Garva R, Krstic-Demonacos M, Demonacos C. Cytochrome P450 2E1 (CYP2E1) regulates the response to oxidative stress and migration of breast cancer cells, Breast Cancer Res. 2013 Nov 8;15(6):R107. [Epub ahead of print]

13.Tian K, Demonacos C and Krstic-Demonacos M, Personalizing Breast Cancer Therapy,  Global Journal of Breast Cancer Research, vol 1, 8-14, 2013, http://dx.doi.org/10.14205/2309-4419.2013.01.01.2

14. Chen DW, Saha V, Liu JZ, Schwartz JM, Krstic-Demonacos M, Erg and AP-1 as determinants of glucocorticoid response in acute lymphoblastic leukemia, Oncogene. 2013 Jun 20;32(25):3039-48. doi: 10.1038/onc.2012.321. Epub 2012 Aug 6.

15.  Simic I, Adzic M, Maric N, Savic D, Djordjevic J, Mihaljevic M, Mitic M, Pavlovic Z, Soldatovic I, Krstic-Demonacos M, Jasovic-Gasic M, Radojcic M. A preliminary evaluation of leukocyte phospho-glucocorticoid receptor as a potential biomarker of depressogenic vulnerability in healthy adults, Psychiatry Res. 2013 Mar 7. pii: S0165-1781(13)00057-7.

16.  Rajendran R, Garva R, Ashour H, Leung T, Stratford I, Krstic-Demonacos M, Demonacos C. Acetylation mediated by the p300/CBP-associated factor determines cellular energy metabolic pathways in cancer, Int J Oncol. 2013 Jun;42(6):1961-72. doi: 10.3892/ijo.2013.1907. Epub 2013 Apr 17.

17. Adzic M, Lukic I, Mitic M, Djordjevic J, Elakovic I, Djordjevic A, Krstic-Demonacos M, Matic G, Radojcic M.,Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism. Psychoneuroendocrinology. 2013 Aug 7. pii: S0306-4530(13)00269-2.

18. Tian K, Rajendran R, Doddananjaiah M, Krstic-Demonacos M, Schwartz JM, Dynamics of DNA damage induced pathways to cancer. PLoS One. 2013 Sep 4;8(9):e72303. doi: 10.1371/journal.pone.0072303.

19.  Ilhem Berrou, Marija Krstic-Demonacos and Constantinos Demonacos. (2012). Molecular mechanisms conferring resistance/sensitivity to glucocorticoid-induced apoptosis. In Xiaoxiao Qian (Ed.), Glucocorticoids. (pp. 151-174). ISBN 980-953-307-128-7, InTech. 2012

20. Qattan M, Demonacos C and Krstic-Demonacos M, Roadmap to personalised medicine, Croat Med J. Aug 15;53(4):294-297, 2012

21.  Andreou K, Rajendran R, Krstic-Demonacos M, and Demonacos C, Regulation of CXCR4 gene expression in breast cancer cells under diverse stress conditions, Int J Oncol. 2012 Dec;41(6):2253-9. doi: 10.3892/ijo.2012.1643. Epub 2012 Sep 27.

22. Chen DW, Krstic-Demonacos M, Schwartz JM, Modeling the Mechanism of GR/c-Jun/Erg Crosstalk in Apoptosis of Acute Lymphoblastic Leukemia, Front Physiol. 2012;3:410. doi: 10.3389/fphys.2012.00410. Epub 2012 Nov 19.

23.Chakraborty A, Bodipati N, Demonacos MK, Peddinti R, Ghosh K, Roy P, Long term induction by pterostilbene results in autophagy and cellular differentiation in MCF-7 cells via ROS dependent pathway, Mol Cell Endo, 355(1):25-40,2012

24. Radojcic M, Adzic M, Niciforovic A, Djordjevic J, Djordjevic A, Demonacos C and Krstic-Demonacos M, Effects of Chronic Psychosocial Isolation on Limbic Brain Structures of Wistar Rats, Glucocorticoids: Effects, Action Mechanisms, and Therapeutic Uses,  Ed: Andres Costa and Eugenio Villalba, Horizons NeurosciRes.Series, Vol 5,Ch4, 97-126, 2012

25. Rajendran R, Garva R, Krstic-Demonacos M and Demonacos C, Sirtuins: molecular traffic lights in the crossroad of oxidative stress, chromatin remodelling and transcription, J Biomed Biotech, 368276, 2011

26. Davies L, Paraskevopoulou E, Sadeq M, Symeou C, Pantelidou C, Demonacos C and Krstic-Demonacos M, Regulation of glucocorticoid receptor function by the stress responsive cofactor, Mol Endocrinology,25, 58-71, 2011

27. Chen D, Lynch JT, Demonacos C, Krstic-Demonacos Mand Schwartz JM, Quantitative analysis and modeling of glucocorticoid controlled gene expression, Pharmacogenomics,11(11), 1545–1560, 2010

28. Lynch JT, Rajendran R, Xenaki G, Demonacos C and Krstic-Demonacos M, The role of glucocorticoid receptor phosphorylation in Mcl-1 and NOXA gene expression, Mol Cancer, Feb 15, 9:38, 2010

29. Popovic N, Ruzdijic S, Kanazir DT, Niciforovic A, Radojcic M, Demonacos C, and Krstic-Demonacos M, Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation, Steroids, 75, 457-465, 2010

30. Adzic M, Djordjevic A, Krstic-Demonacos M, Radojcic MB, Stress-induced phosphorylation of c-jun-n-terminal kinases and nuclear translocation of hsp70 in the Wistar rat hippocampus, Arch BiolSci,  61, 1-8, 2009

31. Adzic M, Djordjevic A, Demonacos C, Krstic-Demonacos M, Radojcic M, The role of pGR in mitochondrial functions and apoptotic signalling in brain tissue of stressed Wistar rats. Int.J.Biochem.Cell Biol., 41, 2181-2188, 2009

32. Adzic M, Djordjevic J, Djordjevic A, Niciforovic A, Demonacos C, Radojcic M, and Krstic-Demonacos M, Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain, J.Endocrinology 202, 1-14, 2009

33. Popovic N, Niciforovic A, Adzic M, Radojcic MB, Demonacos C, and Krstic-Demonacos M, Western blot analysis of glucocorticoid receptor phosphoisoforms by one- and two dimensional electrophoretic assays, J Ser Chem Soc, 74, 237–244, 2009

34. Xenaki G, Onikatze T, Stratford IJ, Dive C, Krstic-Demonacos M, Demonacos, C, PCAF is a HIF-1α cofactor that regulates p53 transcriptional activity in hypoxia, Oncogene, 27, 5785-5796, 2008

35. Davies L, Karthikeyan K, Lynch JT, Sial EA,  Gkourtsa A, Demonacos C and Krstic-Demonacos M, Crosstalk of Signalling Pathways in the Regulation of the Glucocorticoid Receptor Function, Mol Endocrinol, 22, 1331-1344, 2008

36. Demonacos C, Krstic-Demonacos M, Smith L, Xu D,  O'Connor DP, Jansson M, La Thangue NB,  A new effector pathway links ATM kinase with the DNA damage response, Nat Cell Biol, 6, 968-976, 2004

37. Terzic N, Vujcic M, Ristic-Fira A, Krstic-Demonacos M, Milanovic D, Kanazir DT, Ruzdijic S,Effects of Age and Dexamethasone Treatment on GRE and AP-1 Binding Activity in Rat Brain,, J Gerontol A Biol Sci Med Sci, 58, 297-303, 2003

38. Ruzdijic S, Terzic N, Kanazir S, Krstic-Demonacos M, Kanazir DT, Ageing of the brain and glucocorticoids, In: Molecular Mechanisms of Action of Steroid Hormone Receptors, Ed: Krstic-Demonacos M, and Demonacos C, Research Signpost, 25-38, 2002

39. Demonacos C Krstic-Demonacos M and La Thangue NB,  A TPR motif cofactor contributes to p300 activity in the p53 response, Mol Cell, 8, 71-84, 2001

40. Chan HM, Krstic-Demonacos M, Smith L, Demonacos C, and La Thangue NB, Acetylation control of the retinoblastoma tumor suppressor protein, Nat Cell Biol, 3, 667-674, 2001

41. Krstic-Demonacos M, and Demonacos C, Post-translational modifications of steroid receptors, In: Recent Research Developments in Molecular and Cellular Biology, Ed: Pandalai,S.G. Research Signpost, 2, 57-80, 2001

42. Ruzdijic S, Milosevic J, Popovic N, Pesic M, Stojiljkovic M, Kanazir S, Todorovic D, Ristic-Fira A, Krstic-Demonacos M, Kanazir D and RakicLj, Downregulation of c-fos and c-myc expression and apoptosis induction by tiazofurin and 8-Cl-cAMP in human melanoma cells. Yugoslav Med Biochem, 20, 9-18, 2001

43. Shikama N, Chan HM, Krstic-Demonacos M, Smith L, Lee CW, Cairns W and La Thangue, NB, Functional interaction between nucleosome assembly proteins and p300/CREB binding protein family coactivators, Mol Cell Biol, 20, 8933-8943, 2000

44. Djordjevic-Markovic R, Radic O, Jelic V, Radojcic M, Rapic-Otrin V, Ruzdijic S, Krstic-Demonacos M, Kanazir S and Kanazir D, Glucocorticoid receptors in ageing rats, Experimental Gerontology, 34, 971-982, 1999

45. Ristic-Fira A, Vujcic M, Krstic-Demonacos M, and Kanazir D, Identification and characterization of glucocorticoid receptors in B16 mouse melanoma cells, Endocrine Regulations, 33, 109-115, 1999

46. Shikama N, Lee C-W, France S, Delavaine L, Lyon J, Krstic-Demonacos M, and La Thangue NB, A novel cofactor for p300 that regulates the p53 response, Mol Cell, 4, 365–376, 1999

47. GarabedianMJ, Rogatsky I, Hittelman A, Knoblauch R, Trowbridge JM, and Krstic, MD  Regulation of glucocorticoid and estrogen receptor activity by phosphorylation Molecular Biology of Steroid and Nuclear Hormone Receptors, Birkhauser Boston, Ed: Freedman, L., 237-260, 1998

48. Pocuca N, Ruzdijic S, Demonacos C, Kanazir D and Krstic-Demonacos M, Using yeast to study glucocorticoid receptor phosphorylation, J Steroid BiochemMolBiol, 66, 303-318, 1998

49. Krstic M, Steroid receptors and their changes in malignant cells,  In: Molecular mechanisms of cell function, Serbian Academy of Sciences and Arts, Vinca Institute of Nuclear Sciences, Faculty of Biology, University of Belgrade, eds: RakicLJ, Ribarac-Stepic N, Simic D, 157-164, 1997

50. Krstic MD, Rogatsky I, Yamamoto KR, GarabedianMJ, Mitogen-activated and cyclin-dependent protein kinases selectively and differentially modulate transcriptional enhancement by the glucocorticoid receptor, Mol Cell Biol, 17, 3947-3954, 1997

51. Djordjevic-Markovic R, Kanazir DT, Krstic M, Dimitrijevic M and Susa S, Altered structure of steroid receptors in kidney malignancy, Radiation Protection, Ed: O. F. Nygaard, Plenum Publishing Corp, New York, 383-389, 1991

52. Djordjevic-Markovic R, Krstic M, Ribarac-Stepic N, Susa S, Kanazir DT, Steroid receptors in nonmalignant and malignant kidney tissue of patients with endemic Balkan nephropathy, Endocrine Regulations, 25, 199-205, 1991

53. Krstic M, Djordjevic-Markovic R, Susa S, Kanazir D, Steroid receptor analysis in human kidney adenocarcinoma, Bulletin de l AcademieSerbe des Sciences et des Arts, SciNaturelles, 32, 67-77, 1990

54. Radojcic M and Krstic M, Steroid receptors: triggering elements of the transcriptional machinery, Genetika, 21, 1-19, 1989