Suzana Savkovic, Ph.D.

Associate Professor

Tulane Cancer Center Member - Cancer Biology Research Program
Phone
504-988-1409
Office Address
School of Medicine Department of Pathology & Laboratory Medicine 1430 Tulane Ave., SL-79 New Orleans, LA 70112
School of Medicine
Department
Pathology Laboratory Medicine
Diabetes Research
Tulane Cancer Center
Suzanna Savkovic, PhD

Education & Affiliations

1988 B.S. Molecular Biology and Physiology, University of Belgrade, Serbia
1992 M.S. Molecular Biology and Genetics Engineering, University of Belgrade, Serbia,
1999 Ph.D. University of Illinois at Chicago/ University of Belgrade Serbia
1999 – 2006: Postdoctoral fellow and Research Assistant professor, Mentor: Gail Hecht, MD, University of Illinois at Chicago

Biography

After graduating from the Molecular Biology program at the University of Belgrade in Yugoslavia, the Institute for Molecular Biology and Genetic Engineering accepted Dr. Savkovic into their graduate program. Soon after finishing her MS thesis, she accepted an invitation to be part of a team working on the Genome Project at the Argonne National Laboratory in the U.S. Although this project was exciting, her desire to continue with academic science transpired after meeting Dr. Gail Hecht at the University of Illinois in Chicago. After finishing her Ph.D., through which she sought to understand the mechanism of intestinal inflammation, and with the support of her mentor, Dr. Savkovic's post-graduate projects received Crohn’s and Colitis Foundation of America Fellowship and Career Development Awards. While her interests have expanded towards understanding how inflammation fosters tumor growth, which is often seen among patients with ulcerative colitis, she was searching for an institution with a strong cancer program. As a result, she landed her first independent position at the Research Institution of Evanston-Northwestern Healthsystem, which was part of Northwestern University and then later became associated with the University of Chicago. Her main research focus at the time was to study the role of the transcription factor FOXO3 in inflammation-mediated tumor growth, with a specific focus on the colonic epithelium and colon cancer. These projects were awarded the Crohn’s and Colitis Foundation of America Senior Investigator Award and an NIH R01 grant. In 2013, Dr. Savkovic joined Tulane University and became a member of the Cancer Center in the hopes of further understanding the regulation of FOXO3-dependent metabolic pathways that provide fuel energy to support inflammation and tumor growth.

Faculty Appointments

2006–2010: Research Assistant Professor, (Evanston-Northwestern-HealthSystem and Northwestern University, Evanston IL)
2010–2013: Assistant Professor (Northshore University HealthSystem, Evanston IL)
2013–Present: Associate Professor, Tulane University School of Medicine

Teaching and Mentoring Activities

1994–2013: Actively participating in training activities of Department of Medicine, Section of Digestive Disease at previous institutions.
2013–present: Lectures for BMS Tulane Graduate Students: Cell Signaling
2017–present: Co-director Molecular and Cellular Biology Principles and Technologies- MS Molecular Medicine
2007–present: Actively participating in mentoring graduate and post-graduate students.

Research

The main focus of my lab has been to study the role of the transcription factor FOXO3 in inflammation-mediated tumor growth, with a specific focus on the colonic epithelium and colon cancer. First, we have demonstrated that proinflammatory stimuli, such as bacterial products and cytokines, cause a loss of FOXO3 activity, leading to sustained inflammation in colonic epithelial cells, while deficiency of FOXO3 in mice increases susceptibility to colonic inflammation. Second, growth factors, known to support tumor progression, also cause loss of FOXO3, thus stimulating colonic tumor cell growth by loss of cell cycle arrest. These in vitro findings were confirmed in vivo, where a deficiency in FOXO3 lead to increased growth and promotion of colonic tumors, while inhibition of FOXO3 loss suppressed the growth of colonic tumor cells. Thus, as FOXO3 has anti-inflammatory and tumor suppressor functions in colonic cells, thus most likely the loss of FOXO3 is one of the contributors to inflammation-promoted tumor growth in the colon. Third, we found that FOXO3-deficient mice have increased accumulation of intracellular lipid droplets (LDs) and demonstrated the presence of cross-talk between FOXO3 and LDs as part of a regulatory network in colonic epithelial cells (non-transformed and transformed). Since inflammation and tumor growth have high metabolic needs, our goal is to determine that loss of FOXO3, which leads to increased LD accumulation, might provide metabolic energy to fuel inflammation and tumor growth and thus open an opportunity to establish new therapeutic approaches suppressing inflammation and tumor growth in the colon. 

Epidemiological studies have found polymorphisms in the FOXO3 promoter in obese individuals. Moreover, increased intracellular accumulation of LDs characterizes obesity, thus potentially linking the regulatory network of FOXO3 and LDs with obesity. Since obesity is associated with inflammation (including intestinal inflammation), the cross-talk between FOXO3 and LDs may contribute to the increased risk of colonic tumors of obese subjects. Therefore, the second major focus of our lab is to determine the role of the LD-FOXO3 network in modulating susceptibility to colon tumor growth in experimental models of obesity-associated tumors.

Contributions

  1. Penrose H, Heller S, Cable C, Biswas D, Nakhoul H, Baddoo M, Flemington E,Crawford SE, Savkovic SD. OncoScience, 2017 Dec 27;4(11-12):189-198. doi: 10.18632/oncoscience.386 PMID: 29344557
  2. Reduced mitochondrial activity in colonocytes facilitates AMPKα2 dependent inflammation. Heller S, Penrose H, Cable C, Biswas D, Nakhoul H, Baddoo M, Flemington E,Crawford SE, Savkovic SD. FASEB Journal, 2017 May;31(5):2013-2025. doi: 10.1096/fj.201600976R PMID: 28183804 *Cover page May 2017
  3. In colonic ρ0 (rho0) cells reduced mitochondrial function mediates transcriptomic alterations associated with cancer.
  4. High-fat diet induced leptin and Wnt expression: RNA-sequencing and pathway analysis of mouse colonic tissue and tumors. Penrose H, Heller S, Cable C, Nakhoul H, Baddoo M, Flemington E, Crawford SE, Savkovic SD. Carcinogenesis; Mar 1;38(3):302- 311. doi: 10.1093/carcin/bgx001. PMID: 28426873
  5. Intestinal inflammation requires FOXO3 and Prostaglandin E2 dependent lipogenesis and elevated lipid droplets. Heller S, Cable C, Penrose H, Makboul R, Biswas D, Cabe M, Crawford SE, Savkovic SD. Am J Physiol Gastrointest Liver Physiol. 2016 Mar 11;ajpgi.00407.2015. PMID: 26968210
  6. Epidermal growth factor receptor mediated proliferation depends on increased lipid droplet density regulated via a negative regulatory loop with FOXO3/Sirtuin6. Penrose H, Heller S, Cable C, Chadalawada G, Chen S, Crawford SE, Savkovic SD. Biochem Biophys Res Commun. 2016 Jan 15;469(3):370-6. PMID: 26657850
  7. Decreased FOXO3 within advanced human colon cancer: implications of tumor suppressor function. Savkovic SD. Br J Cancer. 2013 Jul 23;109(2):297-8. PMID: 23828519
  8. FOXO3 Growth Inhibition of Colonic Cells is Dependent on Intraepithelial Lipid Droplet Density. Qi W, Fitchev P, Cornwell M, Greenberg J, Cabe M, Weber CR, Roy H, Crawford S, Savkovic SD. J Biol Chem. 2013 Jun 7;288(23):16274-81. PMID: 23603907
  9. Topical Polyethylene Glycol as a Novel Chemopreventive Agent for Oral Cancer via Targeting of Epidermal Growth Factor Response. Wali R, Kunte D’ De La Cruz M, Tiwari A, Brasky J, Weber CR, Gibson T, Patel A, Savkovic SD, Brockstein B, Roy HK. PLoS One. 2012;7(6):e38047. PMID: 22675506
  10. Polyethylene glycol (PEG) diminishes pathological effects of Citrobacter rodentium infection by blocking bacterial attachment to the colonic epithelia. Qi W, Joshi S, Weber CR, Wali R, Roy H, Savkovic SD. Gut Microbes. 2011 Sep 1;2(5):267-73. PMID: 22067938
  11. Genistein inhibits proliferation of colon cancer cells by attenuating a negative effect of epidermal growth factor on tumor suppressor FOXO3 activity. Qi W, Weber CR, Wasland K, Savkovic SD. BMC Cancer. 2011 Jun 3;11:219. PMID: 21639915
  12. Tumor suppressor FOXO3 mediates signals from the EGF receptor to regulate proliferation of colonic cells. Qi W, Weber CR, Wasland K, Roy H, Wali R, Savkovic SD. Am J Physiol Gastrointest Liver Physiol. 2011 Feb;300(2):G264-72. PMID: 21109589
  13. Tumor suppressor FOXO3 participates in the regulation of intestinal inflammation. Snoeks L, Weber CR, Wasland K, Turner JR, Vainder C, Qi W, Savkovic SD. Lab Invest. 2009 Sep;89(9):1053-62. PMID: 19636295
  14. Tumor suppressor Foxo3a is involved in the regulation of LPS-induced IL-8 in intestinal HT- 29 cells. Snoeks L, Weber CR, Turner JR, Bhattacharyya M, Wasland K, Savkovic SD. Infect Immun. 2008 Oct;76(10):4677-85. PMID: 18678662
  15. Mouse model of enteropathogenic Escherichia coli infection. Savkovic SD, Villanueva J, Turner JR, Matkowskyj KA, Hecht G. Infect Immun. 2005 Feb;73(2):1161-70. PMID: 15664959
  16. Differing roles of protein kinase C-zeta in disruption of tight junction barrier by enteropathogenic and enterohemorrhagic Escherichia coli. Tomson FL, Koutsouris A, Viswanathan VK, Turner JR, Savkovic SD, Hecht G. Gastroenterology. 2004 Sep;127(3):859- 69. PMID: 15362041
  17. PKC zeta participates in activation of inflammatory response induced by enteropathogenic E. coli. Savkovic SD, Koutsouris A, Hecht G. Am J Physiol Cell Physiol. 2003 Sep;285(3):C512- 21. PMID: 12900386
  18. Intestinal epithelial responses to enteric pathogens: Effects on the tight junction barrier, ion transport, and inflammation. Berkes J, Viswanathan VK, Savkovic SD, Hecht G. Gut. 2003 Mar;52(3):439-51. PMID: 12584232 (Review)
  19. EPEC-activated ERK1/2 participate in inflammatory response but not tight junction barrier disruption. Savkovic SD, Ramaswamy A, Koutsouris A, Hecht G. Am J Physiol Gastrointest Liver Physiol. 2001 Oct;281(4):G890-8. PMID: 11557508
  20. Galanin-1 receptor up-regulation mediates the excess colonic fluid production caused by infection with enteric pathogen. Matdowskyj KA, Danilkovich A, Marrero JA, Savkovic SD, Hecht G, Benya RV. Nat Med. 2000 Sep;6(9):1048-51. PMID: 10973327
  21. Infection of intestinal epithelial cells with bacterial pathogens decreases luciferase activity: Ramifications for reporter gene studies. Savkovic SD, Koutsouris A, Wu G, Hecht G. Biotechniques. 2000 Sep;29(3):514-6, 518-20, 522. PMID: 10997265
  22. Pathogenic Escherichia coli increase Cl- secretion from intestinal epithelia by upregulating galanin-1 receptor expression. Hecht G, Marrero JA, Danilkovich A, Matkowskyj KA, Savkovic SD, Koutsouris A, Benya RV. J Clin Invest. 1999 Aug;104(3):253-62. PMID: 10430606
  23. Activation of NF-kappaB in intestinal epithelial cells by enteropathogenic Escherichia coli. Savkovic SD, Koutsouris A, Hecht G. Am J Physiol. 1997 Oct;273(4 Pt 1):C1160-7. PMID: 9357759
  24. Effector role of epithelia in inflammation - Interaction with bacteria. Hecht G, Savkovic SD. Aliment Pharmacol Ther. 1997 Dec;11 Suppl 3:64-8; discussion 68-9. PMID: 9467980
  25. Enteropathogenic Escherichia coli-induced myosin light chain phosphorylation alters intestinal epithelial permeability. Yuhan R; Koutsouris A, Savkovic SD, Hecht G. Gastroenterology. 1997 Dec;113(6):1873-82. PMID: 9394726
  26. Attachment of a noninvasive enteric pathogen, enteropathogenic Escherichia coli, to cultured human intestinal epithelial monolayers induces transmigration of neutrophils. Savkovic SD, Koutsouris A, Hecht G. Infect Immun. 1996 Nov;64(11):4480-7. PMID: 8890195
  27. Molecular evidence for increased hematopoietic proliferation in the spleen of the b/b laboratory rat. Savkovic S, Pavlovic S, Mitrovic T, Joksimovic M, Marjanovic J, Glisin V, Popovic Z. Experientia. 1996 Aug 15;52(8):807-11. PMID: 8774753
  28. Genome-scale DNA sequence recognition by hybridization to short oligomers. Milosavljevic A, Savkovic S, Crkvenjakov R, Salbego D, Serrato H, Kreuzer H, Gemmell A, Batus S, Grujic D, Carnahan S, Tepavcevic J. Proc Int Conf Intell Syst Mol Biol. 1996;4:176-81. PMID: 8877517
  29. DNA sequence recognition by hybridization to short oligomers: experimental verification of the method on the E. coli genome. Milosavljevic A, Savkovic, S, Crkvenjakov R, Salbego D,
  30. Serrato H, Kreuzer H, Gemmell A, Batus S, Grujic D, Carnahan S, Paunesku T, Tepavcevic J. Genomics. 1996 Oct 1;37(1):77-86. PMID: 8921373
  31. The disbalance of alpha and beta globins in anemic Belgrade rat red blood cells. Marjanovic J, Savkovic,S, Nikcevic G, Glisin V, Ivanovic Z. Milenkovic N, Popovic Z. Biochem Biophys Res Commun. 1994 May 30;201(1):115-22. PMID: 8198563
  32. The "b" mutated gene in heterozygous Belgrade anemic rat. Popovic ZB, Rajic NV, Savkovic SD, Glisin VR. Exp Hematol. 1993 Jan;21(1):21-4. PMID: 8417956

Presentations

Over 50 Abstracts presented as a first or senior author at national and international meetings

American Gastroenterological Association (AGA):

  • San Francisco, CA, 1996
  • Washington, DC, 1997
  • Orlando, FL, 1999
  • San Diego, CA, 2000
  • Atlanta, GA, 2001
  • San Francisco, CA, 2002
  • Orlando, FL, 2003
  • New Orleans, LA, 2004
  • Los Angeles, CA, 2006
  • Washington DC, 2007
  • San Diego, CA, 2008
  • Chicago, IL, 2009
  • New Orleans, LA, 2010
  • Chicago, IL, 2011
  • San Diego, CA, 2012
  • Orlando, FL, 2013
  • Washington, DC, 2015
  • Chicago, IL, 2017

Experimental Biology (EB):

  • San Diego, CA, 2014

Federation of American Societies of Experimental Biology (FASEB):

  • Colorado, 1996
  • Montana, 2001
  • Colorado, 2005
  • Colorado, 2007
  • Vermont, 2014
  • Colorado, 2015

Invited Speaker

  • Northwestern University - IBD Retreat, Chicago, 2002
  • John Hopkins University - IBD Retreat, Baltimore, 2005
  • University of Chicago - Chicago, 2006
  • University of New Mexico - Albuquerque, 2006
  • University of Chicago - Chicago, 2009
  • University of Illinois – Chicago, 2010
  • Midwestern University – Downers Grow, 2012
  • University of Connecticut - Farmington, 2012
  • University of Illinois – Chicago, 2012
  • University of Missouri – Columbus, 2012
  • Tulane University – New Orleans, 2013
  • Department of Structural & Cellular Biology, Tulane University, 2014
  • Department of Biochemistry & Molecular Biology, Tulane University, 2013
  • Department of Physiology, Tulane University, 2014
  • Metabolic Center, Tulane University, 2015
  • Hayward Genetics Center; Tulane University Medical Center, 2015
  • Metabolic Center, Tulane University, 2017
  • Department of Pathology, Tulane University, 2017