Duska Maria Separovic Ph.D.
EACPHS, Room 3144
Associate Professor (research)
Department of Pharmaceutical Sciences
Degrees and Certifications
1979 B.S. Biology, Faculty of Science, University of Zagreb, Croatia
1979 Certificate in Secondary Education, Faculty of Science, University of Zagreb, Croatia
1985 M.S. Preclinical Pharmacology, School of Medicine, University of Zagreb, Croatia
1992 Ph.D. Neurosciences (Minor in Neurochemistry), Kent State University, Kent, OH
1993 Postdoctoral Fellow in Biochemistry, Case Western Reserve University, Cleveland, OH
Positions and Employment
2010 Associate Professor (Research), Dept. of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy & Health Sciences, Wayne State University, Detroit, MI
2002 Scientific Member, Karmanos Cancer Institute, Detroit, MI
Awards and Honors
2R01 CA077475, National Cancer Institute, NIH, Sphingolipids in Cell Death after Photodamage.Role: Principal Investigator, 08/2009-07/2013.
1R01 CA077475, National Cancer Institute, NIH, Ceramide Production in Photosensitized ApoptoticCells. Role: Principal Investigator, 04/2005-03/2008.
R29 CA077475, National Cancer Institute, NIH, A Role of Ceramide in Mediating PDT-InducedApoptosis. Role: Principal Investigator, 12/1998-11/2003.
2004 American Society for Biochemistry and Molecular Biology
1996 American Society for Pharmacology and Experimental Therapeutics
1997-2007 American Society for Photobiology
1992-1993 American Society for Neurochemistry
Primary Research Interest
Photodynamic therapy (PDT), a type of cancer treatment that bypasses most of the problems associated with resistance to chemotherapy, produces in cells sphingolipids that are important in destroying cancer cells. We are interested in deepening our understanding of the regulation of sphingolipid metabolism after PDT, the role of sphingolipids in promoting cell death post-PDT, and in identifying drugs that are responsible for increasing the amounts of those sphingolipids that help killing cancer cells after PDT to enhance therapeutic value of PDT.
Dolgachev V, Faroqui SM, Nagy B, Kulaeva OI, Tainsky MA, Hanada K. and Separovic D. De novo ceramide accumulation due to inhibition of its conversion to complex sphingolipids in apoptotic photosensitized cells. Journal of Biological Chemistry, 279:23238-23249, 2004.
Dolgachev V, Oberley LW, Huang T-T, Kraniak JM, Tainsky AM, Hanada K, Separovic D. A role for manganese superoxide dismutase in apoptosis after photosensitization. Biochemical and Biophysical Research Communications, 332:411-417, 2005.
Separovic D, Wang S, Maitah MYA, Hanada K, Kessel D. Ceramide response post-photodamage is absent after treatment with HA14-1. Biochemical and Biophysical Research Communications, 345: 803-808, 2006.
Separovic D, Hanada K, Maitah, MYA, Nagy B, Hang I, Tainsky MA, Kraniak JM, Bielawski J. Sphingomyelin synthase 1 suppresses ceramide production and apoptosis post-photodamage. Biochemical and Biophysical Research Communications, 358:196-202, 2007.
Separovic D, Semaan L, Tarca AL, Maitah MYA, Hanada K, Bielawski J, Villani M, Luberto C. Suppression of sphingomyelin synthase 1 by small interference RNA is associated with enhanced ceramide production and apoptosis after photodamage. Experimental Cell Research, 314:1860-1868, 2008.
Separovic D, Bielawski J, Pierce JS, Merchant S, Tarca AL, Ogretmen B, Korbelik M. Increased tumour dihydroceramide production after Photofrin-PDT alone and improved tumour response after the combination with exogenous ceramide analog LCL29. Evidence from mouse squamous cell carcinomas. British Journal of Cancer, 100: 626-632, 2009.
Separovic D, Kelekar A, Nayak AK, Tarca AL, Hanada K, Pierce JS, Bielawski J. Increased ceramide accumulation correlates with downregulation of the autophagy protein ATG-7 in MCF-7 cells sensitized to photodamage. Archives of Biochemistry and Biophysics, 494:101-105, 2010.
Separovic D, Bielawski J, Pierce JS, Merchant S, Tarca AL, Bhatti G, Ogretmen B, Korbelik M. Enhanced tumor cures after Foscan photodynamic therapy combined with the ceramide analog LCL29. Evidence from mouse squamous cell carcinomas for sphingolipids as biomarkers of treatment response. International Journal of Oncology. In press.
Separovic D, Saad ZH, Edwin EA, Bielawski J, Pierce JS, Bielawska A. Enhanced total ceramide levels correlate with augmented overall cell killing after C16-ceramide analog combined with Pc 4 photodynamic therapy. Evidence for promotion of DEVDase activation in the absence of apoptosis. Journal of Lipids. In press.