BIOGRAPHICAL SKETCH NAME Natalie J. Serkova, Ph.D. POSITION TITLE Associate Professor of Anesthesiology, Pharmacology and Radiology DEGREE YEAR(s) FIELD OF STUDY INSTITUTION AND LOCATION Joseph Fourier University, Grenoble, France B.S. Shevchenko University, Kiev, Ukraine M.S. University of Bremen, Germany Ph.D. University of California, San Francisco, CA Post-doc eRA Commons User Name: HSC.SERKOVA.NATALIE 1991 1992 1996 1997-1999 Physics Biophysics Biochemistry/ RadiologSci Clinical Pharmacokinetics A. Personal Statement As Director of the University Colorado Cancer Center (UCCC) and Colorado Clinical Translational Institute (CCTSI) Imaging and Metabolomics Core, I have been actively involved in basic and translational research, as well as clinical trials utilizing imaging and metabolomics end-points for inflammation, drug toxicity, cancer detection, staging and therapy response. My own research interests and expertise are in the area of NMRbased metabolomics and functional imaging (including MRI, MRS and PET/CT) to predict cancer response to novel signal transduction inhibitors. My facility, in collaboration with various laboratories from CU Boulder and Colorado School of Mines, is also active in development novel molecular imaging probes/ nanoparticles for MRI and CT imaging. We apply fast T1- and T2-MRI maps for quantitative assessment of superparamagnetic iron oxide and gadolinium nanoparticles in animal models as well as in research human studies. Most recently, together with the Radiochemistry Facility (Radiology Department) we are involved in developing and imaging new PET tracers. In this project, my team and I will provide all imaging-related technical expertise including protocol development, image acquisition and help with imaging analysis. B. Positions and Employment 1998-1999 Supervisor of Animal MRI/MRS Laboratory, Departments of Pharmaceutical Chemistry and Biopharmaceutical Sciences, University of California, San Francisco. 1999-2000 Visiting Assistant Professor, Department of Biopharmaceutical Sciences, University of California, San Francisco. 1999-2002 Assistant Professor, NMR Division, Institute of Chemistry and Biology, University of Bremen, Germany 2002-2006 Assistant Professor, Department of Anesthesiology, University of Colorado at Denver, Colorado. 2003-present Secondary Faculty Appointment, Department of Pharmacology, UCD. 2004-present Director, Cancer Center Metabolomics Core, UCD. 2005-present Secondary Faculty Appointment, Department of Radiology, UCD. 2006-present Associate Professor, Department of Anesthesiology, Pharmacology and Radiology, UCD. 2008-present Director, Colorado Clinical Translational Science Institute Imaging Core Honors 1993-1996 1997-1999 1998 1999-2002 2004 2005 2006 Postgraduate Scholarship, Deutsche Forschungsgemeinschaft, Bonn, Germany Post-doctoral Scholarship, Alexander-von-Humboldt Foundation, Bonn, Germany Young Investigator and Travel Award of the International Society of Magnetic Resonance in Biological Systems Noether Award (Career Development Award for Outstanding Young Faculty) of the Deutsche Forschungsgemeinschaft, Bonn, Germany New Strategic Research Initiative Award for establishing animal MRI Core by the Academic Enrichment Fund (AEF) of the School of Medicine, UCHSC University of Colorado Cancer Center Start-Up Grant to establish the Biomedical MRI/MRS Core. Generations Cancer Center Fund Award, Denver, CO 2007 New Strategic Research Initiative Award for establishing animal microCT-PET Core by the Academic Enrichment Fund (AEF) of the School of Medicine, UCHSC C. Selected peer-reviewed publications (total 103): Books and Book Chapters Serkova, N.: Effects of immunosuppressive drugs on cell metabolism of neuronal and glial cell lines by multinuclear magnetic resonance spectroscopy (German). ISBN 3-8265-2124-2, Shaker Verlag, Aachen, 1997. Serkova NJ and Glunde K: “Metabolomics in cancer” in Tumor Biomarker Discovery (series Methods in Molecular Biology, ISBN 978-1-60327-810-2, Springer, 2009. Serkova NJ, Hasebroock KM, Kraft SL: “Magnetic resonance spectroscopy of living tissues” in Tumor Biomarker Discovery (series Methods in Molecular Biology, ISBN 978-1-60327-810-2, Springer, 2009. Boyes SG, Rowe MD, Chang CC, Thamm DH, Kraft SL, Harmon JF, Serkova NJ, Vogt AP, Sumerlin BS: “Surface modification of positive contrast nanoparticle agents with RAFT polymers towards the targeted imaging and treatment of cancer” in Polymeric Delivery of Therapeutics (by S. Morgan and R. Lochhead), ISBN13: 978-084-122-5831, Oxford University Press, 2011. 1. Flögel U, Niendorf T, Serkowa N, Brand A, Henke J, Leibfritz D: Change in organic solutes, volume, energy state, and metabolism associated with osmotic stress in glial cell line: A multinuclear NMR study. Neurochem Res 20: 793-802, 1995 [PMID 7477672] 2. Serkova N, Brand A, Christians U, Leibfritz D: Evaluation of the effects of immunosuppressants on neuronal and glial cells in vitro by multinuclear magnetic resonance spectroscopy. Biochim Biophys Acta 1314: 93-104, 1996 [PMID 8972722]. 3. Serkova N, Christians U, Flögel U, Pfeuffer J, Leibfritz D: Assessment of the mechanism of astrocyte swelling induced by the macrolide immunosuppressant sirolimus using multinuclear magnetic resonance (NMR) spectroscopy. Chem Res Toxicol 10: 1359-1363, 1997 [PMID 9437526]. 4. Serkova N, Litt L, James TL, Sadee W, Leibfritz D, Benet LZ, Christians U: Evaluation of individual and combined neurotoxicity of the immunosuppressants cyclosporine and sirolimus by in vitro multinuclear NMR spectroscopy. J Pharmacol Exp Ther 289: 800-806, 1999 [PMID 10215655]. 5. Hausen B, Ikonen T, Briffa N, Berry GJ, Christians U, Robbins RC, Hook L, Serkova N, Benet LZ, Schuler W, Morris RE: Combined immunosuppression with cyclosporine (NeoralR) and SDZ RAD in non-human primate lung transplantation: systematic pharmacokinetic-based trials to improve efficacy and tolerability. Transplantation 69: 76-86, 2000 [PMID 10653384]. 6. Hausen B, Gummert J, Berry GJ, Christians U, Serkova N, Ikonen T, Hook L, Legay F, Schuler W, Schreier MH, Morris RE: Prevention of acute allograft rejection in nonhuman primate lung transplant recipients: Induction with chimeric anti-IL-2 receptor monoclonal antibody improves the tolerability and potencies the immunosuppressive activity of a regimen using low doses of both microemulsion cyclosporine and 40-O-(2-hydroxyethyl)-rapamycin. Transplantation 69: 488-496, 2000 [PMID 10708100]. 7. Serkova N, Litt L, Leibfritz D, Hausen B, Morris RE, James TL, Benet LZ, Christians U: The novel immunosuppressant SDZ-RAD protects rat brain slices from cyclosporine-induced reduction of high-energy phosphates. Br J Pharmacol 129: 485-492, 2000 [PMID 10711346]. 8. Serkova N, Hausen B, Jacobsen W, Berry GJ, Morris RE, Benet LZ, Christians U: Tissue distribution and clinical monitoring of the novel macrolide immunosuppressant SDZ-RAD in primate lung transplant recipients: Interaction with cyclosporine. J Pharmacol Exp Ther 294: 323-332, 2000 [PMID 10871329]. 9. Christians U, Jacobsen W, Serkova N, Benet LZ, Vidal C, Sewing KF, Manns MP, Kirchner GI: Automated, fast and sensitive quantification of drugs in blood by liquid chromatography-mass spectrometry: Immunosuppressants. J Chromatogr B Biomed Sci Appl 748: 41-53, 2000 [PMID 11092585]. 10. Ikonen TS, Gummert JF, Serkova N, Hayase M, Honda Y, Kobayase Y, Hauser B, Yock PG, Christians U, Morris RE: Efficacies of sirolimus (rapamycin) and cyclosporine in allograft vascular disease in non-human primates: trough levels of sirolimus correlate with inhibition of progression of arterial intimal thickening. Transpl Int 13: 314-320, 2000 [PMID 11112022]. 11. Jacobsen W, Serkova N, Hausen B, Morris RE, Benet LZ, Christians U: Comparison of the in vitro metabolism of the macrolide immunosuppressants sirolimus and RAD. Transplant Proc 33: 514-515, 2001 [PMID 11266932]. 12. Serkova N, Jacobsen W, Niemann CU, Benet LZ, Leibfritz D, Christians U: Sirolimus, but not structurally related RAD (everolimus), enhances the negative effects of cyclosporine on mitochondrial metabolism in the rat brain. Br J Pharmacol 133: 875-885, 2001 [PMID 11454661]. 13. Serkova N, Donohoe P, Gottschalk S, Hainz C, Niemann CU, Bickler PE, Litt L, Benet LZ, Leibfritz D, Christians U: Comparison of the effects of cyclosporine A on the metabolism of perfused rat brain slices during normoxia and hypoxia. J Cereb Blood Flow Metab 22: 342-352, 2002 [PMID 11891440]. 14. Niemann CU, Saeed M, Akbari H, Jacobsen W, Benet LZ, Christians U, Serkova N: Close association between the reduction in myocardial energy metabolism and infarct size: dose response assessment of cyclosporine. J Pharmacol Exp Ther 302: 1123-1128, 2002 [PMID 12183671]. 15. Niemann CU, Stabernack D, Serkova N, Jacobsen W, Christians U, Eger EI: Cyclosporine can increase isoflurane MAC. Anesth Analg 95: 930-934, 2002 [PMID 12351270]. 16. Serkova N, Bendrick-Peart J, Alexander B, Tissot van Patot MC: Metabolite concentrations in human term placentae and their changes due to delayed collection after delivery. Placenta 24: 227-235, 2003 [PMID 12566250]. 17. Serkova N, Klawitter J, Niemann CU: Organ-specific metabolic response to cyclosporine treatment in rat liver, kidney and heart. Transplant Int 16: 748-755, 2003 [PMID 12827232]. 18. Wischmeyer PE, Jayakar D, Williams U, Singleton KD, Riehm J, Bacha EA, Jeevanandam V, Christians U, Serkova N: Single dose of glutamine preserves myocardial tissue metabolism, glutathione content, and enhances myocardial function following ischemia-reperfusion injury. J Parenter Enternal Nutr 27: 396-403, 2003 [PMID 14621120]. 19. Fuller TF, Freise CE, Serkova N, Niemann CU, Olson JL, Feng S: Sirolimus delays recovery of rat kidney transplants after ischemia/ reperfusion injury. Transplantation 76: 1594-1599, 2003 [PMID 14702530]. 20. Serkova N and Christians U: Transplantation: Toxicokinetics and mechanisms of toxicity of cyclosporine and macrolides. A review. Curr Opinion Invest Drugs 4: 1287-1296, 2003 [PMID 14758767]. 21. Fuller TF, Serkova N, Niemann CU, Freise CE: Influence of donor pretreatment with N-acetylcysteine on ischemia/reperfusion injury in rat kidney grafts. J Urol 171: 1296-1300, 2004 [PMID 14767336]. 22. Serkova NJ, Christians U, Benet LZ: Biochemical mechanisms of cyclosporine neurotoxicity. A review. Mol Interv 4: 97-107, 2004 [PMID 15087483]. 23. Tissot van Patot MC, Bendrick-Peart J, Beckey VE, Serkova N, Zwerdlinger L: Greater vascularity, lowered HIF-1/DNA binding, and elevated GSH as markers of adaptation to in vivo chronic hypoxia. Am J Physiol Lung Cell Mol Physiol 287: 525-532, 2004 [PMID 15132953]. 24. Christians U, Gottschalk S, Miljus J, Hainz C, Benet LZ, Leibfritz D, Serkova N: Alterations in glucose metabolism by cyclosporine link to oxidative stress in rat brain slices: interactions with mTOR inhibitors. Br J Pharmacol 143: 388-396, 2004 [PMID 15339861]. 25. Gottschalk S, Anderson N, Hainz C, Eckhardt SG, Serkova NJ: Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL positive cells. Clin Cancer Res 10: 6661-6668, 2004 [PMID 15475456]. 26. Boros LG, Serkova NJ, Cascante MS, Lee WNP: Use of metabolic pathway flux information in targeted cancer drug design: A review. Drug Discov Today 1: 435-443, 2004. 27. Serkova N, Fuller TF, Klawitter J, Freise CE, Niemann CU: 1H-NMR-based metabolic signatures of mild and severe ischemia/ reperfusion injury in rat kidney transplants. Kidney Int 67: 1142-1151, 2005 [PMID 15698456]. 28. Singleton KD, Serkova N, Banerjee A, Meng X, Gamboni-Robertson F, Wischmeyer PE: Glutamine attenuates endotoxin-induced lung metabolic dysfunction: Potential role of enhanced heat shock protein 70. Nutrition 21: 214-223, 2005 [PMID 15723751]. 29. Singleton KD, Serkova N, Beckey VE, Wischmeyer PE: Glutamine attenuates lung injury and improves survival following sepsis: Role of enhanced heat shock protein expression. Crit Care Med 33: 1206-1213, 2005 [PMID 15942332]. 30. Serkova N and Boros LG: Detection of resistance to imatinib by metabolic profiling: Clinical and drug development implication: A review. Am J Pharmacogenomics 5: 293-302, 2005 [PMID 16196499]. 31. Niemann CU, Hirose R, Liu T, Behrends M, Brown JL, Kominsky D, Roberts JP, Serkova N: Ischemic preconditioning improves energy state and transplantation survival in obese Zucker rat livers. Anesth Analg 101: 1577-1583, 2005 [PMID 16301222]. 32. Serkova N and Christians U: Biomarkers for toxicodynamic monitoring of immunosuppressants: NMRbased quantitative metabonomics of the blood. Ther Drug Monit 27: 733-737, 2005 [PMID 16404806]. 33. Serkova NJ, Jackman M, Brown JL, Liu T, Hirose R, Roberts JP, Maher JJ, Niemann CU: Metabolic profiling of livers and blood from obese Zucker rats. J Hepatol 44: 956-962, 2006 [PMID 16223541]. 34. Behrends M, Hirose R, Serkova NJ, Coatney JL, Bedolli M, Yardi J, Park YH, Niemann CU: Mild hypothermia reduces the inflammatory response and hepatic ischemia/ reperfusion injury in rats. Liver Int 26: 734-741, 2006 {PMID 16842331]. 35. Peng ZY, Serkova NJ, Kominsky DJ, Brown JL, Wischmeyer PE: Glutamine-mediated attenuation of cellular metabolic dysfunction and cell death following injury is dependent on heat shock factor-1 expression. J Parenter Enteral Nutr 30: 373-378, 2006 [PMID 16931604]. 36. Niemann CU, Choi S, Behrends M, Hirose R, Noh J, Coatney JL, Roberts JP, Serkova NJ, Maher JJ: Mild hypothermia protects obese rats from fulminant hepatic necrosis induced by ischemia-reperfusion. Surgery 140: 404-412, 2006 [PMID 16934602]. 37. Serkova NJ and Niemann CU: Pattern recognition and biomarker validation using quantitative 1H-NMR based metabolomics: A review. Expert Rev Mol Diagn 6: 717-731, 2006 [PMID 17009906]. 38. Glunde K and Serkova NJ: Therapeutic targets and surrogate markers in choline phospholipid metabolism in cancer: A review. Pharmacogenomics 7: 1109-1123, 2006 [PMID 17054420]. 39. Park Y, Hirose R, Coatney JL, Ferell L, Behrends M, Roberts JP, Serkova NJ, Niemann CU: The effect of aging on warm ischemia reperfusion injury in the rat liver. J Surg Res 137: 96-102, 2007 [PMID 17064732]. 40. Rudolph MC, McManaman JL, Phang TL, Anderson SM, Russell T, Kominsky DJ, Serkova NJ, Neville MC: Metabolic regulation in the lactating mouse: A milk lipid synthesizing machine. Physiol Genomics 28: 323-326, 2007 [PMID 17105756]. 41. Serkova NJ, Zhang Y, Coatney JL, Hunter L, Wachs M, Niemann CU, Mandell SM: Early detection of graft failure using the blood metabolic profile of a liver recipient. Transplantation 83: 517-521, 2007 [PMID 17318087]. 42. Serkova NJ, Rose JC, Epperson LE, Carey HV, Martin SL: Quantitative analysis of liver metabolites in three stages of the circannual hibernation cycle in 13-lined ground squirrels by NMR. Physiol Genomics 31: 15-24, 2007 [PMID 17536023]. 43. Niemann CU and Serkova NJ: Biochemical mechanisms of nephrotoxicity: Application for metabolomics: A review. Exp Opin Drug Metab Toxicol 3: 527-544, 2007 [PMID 17696804]. 44. Troiani T, Serkova NJ, Gustafson DL, Henthorn TK, Lockerbie O, Merz A, Long M, Morrow M, Ciardiello F, Eckhardt SG: Investigation of two dosing schedules of vandetanib (ZD6474), an inhibitor of VEGFR and EGFR signaling, in combination with irinotecan in human colon cancer xenograft model. Clin Cancer Res 13: 6450-6458, 2007 [PMID 17975157]. 45. Khan SR, Herman J, Krank J, Serkova NJ, Churchill MEA, Suga H, Farrand SK: PhzR, the quorumsensing regulator of phenazine gene expression in Pseudomonas chlororaphis strain 30-84 responds to N(3-hydroxy-hexanoyl)-L-homoserine lactone and N-hexanoyl)-L-homoserine lactone with equal sensitivity. Appl Environ Micribiol 73: 7443-7455, 2007 [PMID 17921283]. 46. Serkova NJ, Spratlin JL, Eckhardt SG: NMR-based metabolomics: Translational application and treatment of cancer: A review. Curr Opin Mol Ther 9: 572-585, 2007 [PMID 18041668]. 47. Serkova NJ, Reisdorph NA, Tissot van Patot MC: Metabolic markers of hypoxia: Systems biology application in biomedicine. Toxicol Mech Methods 18: 81-95, 2008 [20020894]. 48. Serkova NJ, Gamito EJ, Jones RH, O’Donnell C, Brown JL, Green S, Sullivan H, Hedlund T, Crawford ED: The metabolites citrate, myo-inositol, and spermine are potential age-dependent markers of prostate cancer in human expressed prostatic secretions. Prostate 68: 620-628, 2008 [PMID 18213632]. 49. Serkova NJ, Van Rheen Z, Tobias M, Pitzer J, Wilkinson JE, Stringer KA: Utility of magnetic resonance imaging and nuclear magnetic resonance-based metabolomics for the quantification of inflammatory lung injury. Am J Physiol Lung Cell Mol Physiol 295: L152-L161, 2008 [PMID 18441091]. 50. Larsen BA, Haag MA, Serkova NJ, Shroyer KR, Stoldt CR: Controlled aggregation of superparamagnetic iron oxide nanoparticles for the development of molecular magnetic resonance imaging probes. Nanotechnology 19: 265-271, 2008 [PMID 21828671]. 51. Young CD, Nolte E, Lewis A, Serkova NJ, Anderson SM: Activated Akt1 accelerates MMTV-c-ErbB2 mammary tumorigenesis inc mice without activation of ErbB3. Breast Cancer Res 10: R70, 2008 [PMID 18700973]. 52. Lam ET, O’Bryant CL, Basche M, Gustafson DL, Serkova N, Baron A, Holden S, Dancey J, Eckhardt SG, Gore L: A phase I study of gefitinib, capecitabine, and celexocib in patients with advanced solid tumors. Mol Cancer Ther 7: 3685-3694, 2008 [PMID 19074845]. 53. Serkova NJ, Freud AS, Brown JL, Kominsky DJ: Use of the 1-mm TXI micro-probe for metabolic analysis on small volume biological samples. J Cell Mol Med 13: 1933-1941, 2009 [PMID 19267884]. 54. Frey LC, Hellier J, Unkart C, Lepkin A, Hasebroock K, Serkova N, Liang LP, Patel M, Soltesz I, Staley K: A novel apparatus for lateral fluid percussion injury in the rat. J Neurosci Methods 177: 267-272, 2009 [PMID 19022291]. 55. Spratlin JL, Serkova NJ, Eckhardt SG: Clinical application of metabolomics in oncology: a review. Clin Cancer Res 15: 431-440, 2009 [PMID 19147747]. 56. Serkova NJ, Garg K, Bradshaw-Pierce EL: Oncologic imaging endpoints for the assessment of therapy response. Recent Pat Anticancer Drug Discov 4: 36-53, 2009 [PMID 19149687]. 57. Klawitter J, Anderson N, Klawitter J, Christians U, Leibfritz D, Eckhardt SG, Serkova NJ: Time-dependent effects of imatinib in human leukaemia: A kinetic NMR-profiling study. Br J Cancer 100: 923-931, 2009 [PMID 19259085]. 58. Tissot van Patot MC, Serkova NJ, Haschke M, Kominsky DJ, Roach RC, Sheen P, Christians U, Henthorn TK, Honigman B: Enhanced leukocyte HIF-1alpha and HIF-1 DNA-binding in humans following rapid ascent to 4300 m. Free Radic Biol Med 46: 1551-1557, 2009 [PMID 19303436]. 59. Raina K, Serkova NJ, Agarwal R: Silibinin feeding alters the metabolic profile in TRAMP prostatic tumors: 1 H-NMRS-based metabolomics study (Priority Report). Cancer Res 69: 3731-3735, 2009 [PMID 19366793]. 60. Hasebroock KM, Serkova NJ: Toxicity of MRI and CT contrast agents. Expert Opin Drug Metab Toxicol 5: 403-416, 2009 [PMID 19368492]. 61. Serkova NJ, Glunde K: Metabolomics in cancer. Methods Mol Biol 520: 273-295, 2009 [PMID 19381962]. 62. Serkova NJ, Hasebroock KM, Kraft SL: Magnetic resonance spectroscopy of living tissues. Methods Mol Biol 520: 315-327, 2009 [PMID 19381964]. 63. Kominsky DJ, Klawitter J, Brown JL, Boros LG, Melo JV, Eckhardt SG, Serkova NJ: Abnormalities in glucose uptake and metabolism in imatinib-resistant human BCR-ABL positive cells. Clin Cancer Res 15: 3442-3450, 2009 [PMID 19401345]. 64. Klawitter J, Zhang YL, Klawitter J, Anderson N, Serkova NJ, Christians U: Development and validation of a sensitive assay for the quantification of imatinib using LC/LC-MS/MS in human whole blood and cell culture. Biomed Chromatogr 23: 1251-1258, 2009 [PMID 19517424]. 65. Klawitter J, Kominsky DJ, Brown JL, Klawitter J, Christians U, Leibfritz D, Melo JV, Eckhardt SG, Serkova NJ: Metabolic characteristics of imatinib resistance in chronic myeloid leukaemia cells. Br J Pharmacol 158: 588-600, 2009 [PMID 19663881]. 66. Tissot van Patot MC, Murray AJ, Beckey V, Cindrova-Davies T, Johns J, Zwerdlinger L, Jauniaux ER, Burton GJ, Serkova NJ: Human placental adaptation to chronic hypoxia, high altitude: Hypoxic preconditioning. Am J Physiol Regul Integr Comp Physiol 298: R166-172, 2010 [PMID 19864339]. 67. Serkova NJ: Imaging biochemistry non-invasively: Magnetic resonance spectroscopy in liver disease. Editorial. J Parenter Enteral Nutr 33: 826-728, 2009 [PMID 19892909]. 68. Merz AL and Serkova NJ: Use of NMR-based metabolomics in detecting drug resistance in cancer. Biomark Med 3: 289-306, 2009 [PMID 20160999]. 69. Spratlin JL, Cohen RB, Eadens M, Gore L, Camidge DR, Diab S, Leong S, O’Bryant C, Chow LQ, Serkova NJ, Meropol NJ, Lewis NL, Chiorean EG, Fox F, Youssoufian H, Rowinsky EK, Eckhardt SG: Phase I pharmacologic and biologic study of Ramucirumab (IMC-1121B), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J Clin Oncol 28: 780-787, 2010 [PMID 20048182]. 70. Klawitter J, Gottschalk S, Hainz C, Leibfritz D, Christians U, Serkova NJ: Immunosuppressant neurotoxicity in rat brain models: Oxidative stress and cellular metabolism. Chem Res Tox 23: 608-619, 2010 [PMID 20148532]. 71. Serkova NJ, Renner B, Larsen BA, Stoldt CR, Hasebroock KM, Bradshaw-Pierce EL, Holers VM, Thurman JM: Renal inflammation: Targeted iron oxide nanoparticles for molecular MR imaging in mice. Radiology 255: 517-526, 2010 [PMID 20332377]. Editorial: Mahmood U: Science to practice: can a targeted nanoparticle be used to image autoimmune nephritis? Radiology 255: 309-310, 2010 [PMID 20413745]. 72. Doctor RB, Serkova NJ, Hasebroock KM, Zafar I, Edelstein CL: Distinct patterns of kidney and liver cyst growth in pkd2(WS25-/-) mice. Nephrol Dial Transplant 25: 3496-3504, 2010 [PMID 20388629]. 73. Tentler JJ, Bradshaw-Pierce EL, Serkova NJ, Hasebroock KM, Pitts TM, Diamond JR, Fletcher GC, Bray MR, Eckhardt SG: Assessment of the in vivo antitumor effects of ENMD-2076, a novel multitargeted kinase inhibitor, against primary and cell line-derived human colorectal cancer xenograft models. Clin Cancer Res 16: 2989-2998, 2010 [PMID 20406842]. 74. Vincenti M, Behrends M, Dang K, Park YH, Hirose R, Blasi-Ibanez S, Liu T, Serkova NJ, Niemann CU: Induction of intestinal ischemia reperfusion injury by portal vein outflow occlusion in rats. J Gastroenterol 45: 1103-1110, 2010 [PMID 20549254]. 75. Cohen MJ, Serkova NJ, Wiener-Kronish J, Pittet JF, Niemann CU: 1H-NMR-based metabolic signatures of clinical outcomes in trauma patients – beyond lactate and base deficit. J Trauma 69: 31-40, 2010 [PMID 20622576]. 76. Boyes SG, Rowe MD, Serkova NJ, Kim FJ, Lambert JR, Werahera PN: Polymer-modified gadolinium nanoparticles for targeted magnetic resonance imaging and therapy. NanoLife 1: 263-275, 2010. 77. Stringer KA, Serkova NJ, Karnovsky A, Guire K, Paine R III, Standiford TJ: Metabolic consequences of sepsis-induced acute lung injury revealed by plasma 1H-nuclear magnetic resonance quantitative metabolomics and computational analysis. Am J Physiol Lung Cell Mol Physiol 300: L4-L11, 2011 [PMID 20889676]. 78. Martinez-Palli G, Hirose R, Liu T, Xu F, Dang K, Serkova NJ, Niemann CU: Donor-pretreatment with everolimus or cyclosporine does not reduce ischaemia-reperfusion injury in a rat kidney transplant model. Nephrol Dial Transplant 26: 1813-1820, 2011 [PMID 21068143]. 79. Gottschalk S, Cummins CL, Leibfritz D, Christians U, Benet LZ, Serkova NJ: Age and sex differences in the effects of the immunosuppressants cyclosporine, sirolimus and everolimus on rat brain metabolism. Neurotoxicology 32: 50-57, 2011 [PMID 21075140]. 80. Ramasamy K, Nield L, Serkova NJ, Hasebroock KM, Tyagi A, Raina K, Singh RP, Malkinson AM, Agarwal R: Silibinin prevents lung tumorigenesis in wild-type but not in iNOS-/- mice: Potential of real-time microCT in lung cancer chemoprevention studies. Clin Cancer Res 17: 753-761, 2011 [PMID 21148748]. 81. Hatakeyama WM, Sanchez TJ, Rowe MD, Serkova NJ, Liberatore MW, Boyes SG: Synthesis of gadolinium nanoscale metal-organic framework with hydrotropes: Manipulation of particle size and magnetic resonance imaging capability. ACS Appl Mater Interfaces 3: 1502-1510, 2011 [PMID 21456529]. 82. Spratlin JL, Pitts TM, Kulikowski GN, Morelli MP, Tentler JJ, Serkova NJ, Eckhardt SG: Synergistic results of histone deacetylase and proteasome inhibition against pancreatic and hepatocellular cancer cell lines. Anticancer Res 31: 1093-1103, 2011 [PMID 21508352]. 83. Serkova NJ: Translational imaging endpoints to predict treatment response to novel targeted anticancer agents. Drug Resist Updat 14: 224-235, 2011 [PMID 21640633]. 84. Serkova NJ, Standiford TJ, Stringer KA: The emerging field of quantitative blood metabolomics for biomarker discovery in critical illnesses. Am J Respir Crit Care Med 184: 647-655, 2011 [PMID 21680948]. 85. Sargsyan SA, Serkova NJ, Renner B, Hasebroock KM, Larsen B, Stoldt C, McFann K, Pickering MC, Thurman JM: Detection of glomerular complement C3 fragments by magnetic resonance imaging in murine lupus nephritis. Kidney Int 81: 152-159, 2012 [PMID 21956190]. 86. Morelli MP, Tentler JT, Kulikowski GN, Tan AC, Bradshaw-Pierce EL, Pitts TM, Brown AM, Nallapareddy S, Acaroli JJ, Serkova NJ, Hidalgo M, Ciardiello F, Eckhardt SG: Preclinical activity of the rational combination of selumetinib (AZD6244) in combination with vorinostat in KRAS mutant colorectal cancer models. Clin Cancer Res 18: 1051-1062, 2012 [PMID 22173548]. 87. Serkova NJ, Brown MS: Quantitative analysis in magnetic resonance spectroscopy: from metabolic profiling to in vivo biomarkers. Bioanalysis 4: 321-341, 2012 [PMID 22303835]. 88. Beresford TP, Fay T, Serkova N, Wu PH: Immunophyllin ligands show differential effects on alcohol selfadministration in C57BL mice. J Pharmacol Exp Ther 341: 611-6, 2012 [PMID 22375069]. 89. Larsen BA, Hurst KM, Ashurst WR, Serkova NJ, Stoldt CR: Mono and dialkoxysilane surface modification of superparamagnetic iron oxide nanoparticles for application as magnetic resonance imaging contrast agents. J Material Res 27: 1846-1852, 2012. 90. Raina K, Rajamanickam S, Ravichandran K, Huber KM, Serkova NJ, Agarwal R: Inositol hexaphosphate inhibits tumor growth, vascularity, and metabolism in TRAMP mice: A multiparametric magnetic resonance study. Cancer Res Prev 6: 40-50, 2013 [PMID 23213071]. - January 2013 Cancer Prev Res Journal Cover Page Coverage. 91. Yap TA, Arkenau HT, Camidge DR, George S, Serkova NJ, Gwyther SJ, Spratlin JL, Lal R, Spicer J, Desouza N, Leach M, Chick J, Poondru S, Boinpally R, Gedrich R, Brock K, Stephens A, Eckhardt SG, Kaye S, Demetri G, Scurr M: First-in-human Phase I trial of two schedules of OSI-930, a novel multikinase inhibitor, incorporating translational proof-of-mechanism studies. Clin Cancer Res 19: 909-919, 2013 [PMID 23403628]. 92. Raina K, Agarwal C, Wadhwa R, Serkova NJ, Agarwal R: Energy deprivation by silibinin in colorectalcancer cells: A double edged sword targeting both apoptotic and autophagic machinery. Autophagy 9: 697713, 2013 [PMID 23445752]. 93. Bradshaw-Pierce EL, Pitts TM, Kulikowski G, Selby H, Merz AL, Gustafson DL, Serkova NJ, Eckhardt SG, Weekes CD: Utilization of quantitative pharmacology approach to assess the combination effects of everolimus and irinotecan in murine xenograft models of colorectal cancer. PLoS One 8(3): e58089, 2013 [PMID 23520486]. 94. Weitzel L, Ambardekar AV, Brieke A, Cleveland JC, Serkova NJ, Wischmeyer PE, Lowes BD: Left ventricular assist device effects on metabolic substrates in the failing heart. PLoS One 8(4): e60292, 2013 [PMID 23560088]. 95. Derry M, Raina K, Balaiya V, Jain AK, Shrotriya S, Huber KM, Serkova NJ, Agarwal R, Agarwal C: Grape seed extract efficacy against azoxymethane-induced colon tomorigenesis in A/J mice: Interlinking miRNA with cytokine signaling and inflammation. Cancer Res Prev 6(7): 625-633, 2013 [PMID 23639480]. 96. Wilson J, Higgins D, Hutting H, Serkova N, Baird C, Khailova L, Queensland K, Weitzel L, Tran ZV, Wischmeyer PE: Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis. Crit Care 2013 Sep 10; 17(5): R195. [Epub ahead of print] [PMID 24020447]. 97. Epple LM, Dodd RD, Merz AL, Dechkovskaia AM, Herring M, Winston BA, Lencioni AM, Russell RL, Madsen H, Nega M, Dusto NL, White J, Bigner DD, Nicchitta CV, Serkova NJ, Graner MW: Induction of the unfolded protein response drives enhanced metabolism and chemoresistance in glioma cells. PLoS One 8(8): e73267, 2013 [PMID 24039668]. 98. Yang X, La Rosa FG, Genova EE, Huber K, Schaack J, Degregori J, Serkova NJ, Li Y, Su LJ, Kessler E, Flaig TW: Simultaneous activation of Kras and inactivation of p53 induces soft tissue sarcoma and bladder urothelial hyperplasia. PLoS One 8(9): e74809, 2013 [PMID 24058630]. 99. Frey L, Lepkin A, Schickedanz A. Huber K, Brown MS, Serkova N: ADC mapping and T1-weighted signal changes on post-injury MRI predict seizure susceptibility after experimental traumatic brain injury. Neurol Res 36(1): 26-37, 2014 [PMID 24107461]. 100. Thurman JM, Serkova NJ: Nanosized contrast agents to non-invasively detect kidney inflammation by magnetic resonance imaging. Adv Chronic Kideny Dis 20(6): 488-499, 2013 [PMID 24206601]. 101. Corser-Jensen CE, Goodell DJ, Freund RK, Serbedzija P, Murphy RC, Farias SE, Dell’Acqua ML, Frey LC, Serkova N, Heidenreich KA: Blocking leukotriene synthesis attenuates the pathophysiology of traumatic brain injury and associated cognitive deficits. Exp Neurol 256: 7-16, 2014 [PMID 24681156]. 102. Rudolph MC, Wellberg EA, Lewis AS, Terrel KL, Merz AL, Maluf NK, Serkova NJ, Anderson SM: Thyroid hormone responsive protein Spot14 enhances catalysis of fatty acid synthesis in lactating mammary epithelium. J Lipid Res 55(6): 1052-1065, 2014 [PMID 24771867]. 103. Serkova NJ: New advances and state-of-the-art MR spectroscopy in oncology. Current Molecular Imaging [in press]. D. Research Support Ongoing Research Support 1. NCI P30 CA046934 (Theodorescu) 06/03/2012-01/31/2017 “University of Colorado Comprehensive Cancer Center Core Grant” This is the institutional Cancer Center (UCCC) grant which also provides a significant portion of support for maintaining Cancer Center Shared Resources facilities. The Animal Imaging and Metabolomics Shared Resources (AISR) will be intensively used for this grant. Role: Director of Colorado Animal Imaging and Metabolomics Shared Resources 2. NIH/NCATS UL1TR001082 (Sokol) 09/26/2008 – 04/30/2018 “Colorado Clinical Translational Sciences Institute, CCTSI” The Clinical and Translational Sciences Award (3 grants) to the University of Colorado Denver will support the institutional academic home for research and training in clinical and translational sciences which provides an additional support for maintaining and expanding Shared Resources facilities. The Animal Imaging and Metabolomics Shared Resources (AISR) will be intensively used for this grant. Role: Director of Translational Metabolic and Imaging Core 3. NICHD 1R01HD065534 (PI: Raol) 07/01/2011 – 06/30/2015 “Efficacy of flupirtine for treatment of neonatal hypoxic-ischemic encephalopathy” We will investigate MRI-based changes in developing brain in mouse models for hypoxia-induced encephalopathy and protective role of flupirtine. Role: MRI co-investigator 4. NIDCR R01 DE021788 (PI: Lu) 02/01/2012 – 01/31/2016 “The Role of PI3K Pathway in Head and Neck Cancer Invasion and Metastasis” This project is to evaluate PI3K signal transduction pathways in orthotopic mouse models for human head and neck cancers as well as to assess the effectiveness of PI3K targeted therapeutic intervention. Gadolinium-enhanced MRI as well as 18FDG- and 18fluorine-PET/CT will be employed for early detection and characterization of primary tumors, lung, brain and bone metastasis. Role: Co-investigator 5. NIGM R25 GM103798 (PI: Barnes/ UAB) 08/01/2012 – 07/31/2014 “University of Alabama Metabolomics Workshop: from Design to Decision” This project is in support of the annual Metabolomics Workshop at the University of Alabama at Birmingham. Basic principles of NMR spectroscopy as well as sample handling and extraction, NMR data acquisition and analysis will be taught by Dr. Serkova Role: Co-investigator 6. NIH R01 NS080851-01A1 (Bayer/ Herson) 07/01/2013-06/30/2018 “CaMKII in Global Cerebral Ischemia” The project will evaluate the role of calcineurin in mouse models of cerebral ischemia by applying modern molecular and imaging approaches. Role: Co-investigator for MRI and 18F-tracer PET/MRI studies 7. NIH R01 II066485 (Anchordoquy/ Graner) 07/01/2013-06/30/2018 “Tumor Homing Exosomes for Drug Delivery” This is project is to develop novel 18F-exosome and liposome tracer for molecular PET imaging in mouse cancer models. Metabolic profiling and especially lipidomics of cell-derived exosomes will be established. Role: Co-investigator for NMR Metabolomics and 18F-tracer PET/CT studies. 8. CTSA Novel Method Development Award (Serkova) 05/01/2014-04/30/2015 “Small Animal microCT Colonogrpahy and FDG-PET for Non-Invasive Imaging of Colitis” This project will be focused on developing and validating a high-resolution 3D-virtual colonography (for anatomical measurements) and metabolic FDG-PET (for inflammatory assessment) in inflamed bowel mouse models and colorectal cancer mouse models. Role: Principal Investigator Completed Research Support (last 5 years): NCI 1 R21 CA108624-01 (PI: N. Serkova) 4/01/2005-3/31/2008 “Metabolic signature of imatinib resistance” MRS signature of imatinib resistant human BCR-ABL positive cell lines, the project is focused on glucose and phospholipids metabolism. No overlap with the present project. Role: PI (30%) AEF Award from UCHSC Medical School (PI: N. Serkova) 04/03/2007 – 04/02/2008 “Animal microPET/CT Core at the University of Colorado Cancer Center” This is an instrumentation grant to establish the first in the Region positron emission and computed tomography facility for small rodents. Role: PI and Director (total award amount $900,000) Eli Lilly and Company (PI: N. Serkova) 10/01/2007 - 9/30/200 “Magnetic Resonance Evaluations on Enzastaurin Treatment in Colon Cancer Animal Models” This grant will evaluate metabolic and angiogenic response in human cancer cells in vitro and in mouse xenograft models to the treatment with a novel targeted drug enzastaurin. Role: PI Facet Biotech Corporation (PI: N. Serkova) 08/31/2009 – 09/31/2011 “Pre-Clinical Positron Emission Tomography Evaluations on the Efficacy of PDL192, a Humanized IgG1 monoclonal antibody”. The role of this project is to establish translational PET endpoints for glucose uptake inhibition prior to entering clinical Phase I studies. Role: PI NIH R21 AA016294 (Beresford) 09/30/2008 – 02/29/2012 “Neuro-Immunophyllin Ligand Mechanism of Action in Reducing Alcohol” The major goals of this project are to define role of immunophilins and their inhibition in the brain during alcohol dependency and withdrawal. Role: Co-investigator The AMC Cancer Fund Pilot Grant (Graner/ Serkova/ Waziri) 11/01/2011 – 10/31/2012 “Metabolomics of Glioblastomas and Tumor Tissues in a Novel Organotype Tumor Slice Culture Model: Stress Responses and the Dynamic Tumor Metabolome” In this project, fresh surgical brain tumor specimens will be used for establishing tissue models to investigate changes in primary and recurrent brain tumors. Role: Co-PI CTSA Novel Method Development Award (Serkova) 05/01/2013-04/30/2014 “Iron Oxide Based T2-MRI for Imaging Macrophage Recruitment into Breast Cancer” The project aims to develop a non-invasive magnetic resonance imaging (MRI) technology for real-time detection of TAMs accumulation using superparamagnetic iron oxide (SPIO) nanoparticles. The overall goal of this proposal is to establish and validate quantitative T2/ T2*-MRI maps for assessment of iron accumulation in mouse models of inflamed postpartum breast cancer using FDA-approved SPIO nanoparticles. Role: Principal Investigator