Project Description

Gasper Julius Kitange, MD, Ph.D.

Cancer Therapy Resistance and Drug Target Discovery
Associate Professor

gkitange@umn.edu

Bibliography

Dr. Gasper Kitange is an Associate Professor at The Hormel Institute, University of Minnesota. Dr. Kitange joined Mayo Clinic in Rochester, Minnesota, for post-doctoral training soon after he received Ph.D. degree in Japan. While at Mayo Clinic he moved up his career ladder to become Associate Consultant and Associate Professor. Dr. Kitange’s research interest is focused on understanding the epigenetic regulation of therapy resistance in glioblastoma (GBM), identifying novel molecular targets modulating therapy sensitivity, and develop these targets for therapy in GBM. Dr. Kitange has over 15-year experience in brain tumor research with focus on GBM. He uses high throughput genome wide screening as strategy to identify novel molecular targets for therapy as single agents or for sensitizing the current therapy used for treatment of GBM patients, including radiation and temozolomide. These novel molecular drug targets are validated using biochemical and pharmacologic techniques in vitro and in vivo using patient derived GBM xenografts. Overall, Dr. Kitange has strong expertise in multiple areas of brain tumor research and his current focus is on understanding the epigenetic and non-epigenetic mechanisms that influence the evolution of therapy resistance in GBM and leveraging the results to discovery of novel anticancer agents. Dr. Kitange is NIH funded investigator studying how epigenetic regulates DNA repair genes to enhance recovery from DNA double strand breaks induced by temozolomide.

Education

Muhimbili University of Health and Allied Sciences, Tanzania United Republic – Doctor of Medicine (MD) degree 1986 – 1991

Academic Medical Center, Netherlands – Certificate, Experimental Pharmacology 1990

Nagasaki University School of Medicine, Japan – PhD, Neurological sciences 1995 – 2000

Nagasaki University School of Medicine, Japan – Clinical Fellowship, Neurosurgery 1995 – 2000

Professional memberships

Mayo Clinic Comprehensive Cancer Center — 2020 – present

Society for Neuro-Oncology — 2004 – Present

American Association for Cancer Research — 2000 – Present

Japan Society for Brain Tumor Pathology — 1995 – 01/2000

Japan Society for Neurosurgeons — 1995 – 01/2000

Publications

  1. Kitange GJ, Mladek AC, Schroeder MA, Pokorny JC, Carlson BL, Zhang Y, Nair AA, Lee JH, Yan H, Decker PA, Zhang Z, Sarkaria JN. Retinoblastoma Binding Protein 4 Modulates Temozolomide Sensitivity in Glioblastoma by Regulating DNA Repair Proteins. Cell Rep. 2016 Mar 22; 14 (11):2587-98 Epub 2016 Mar 10 PMID: 26972001 PMCID: 4805508   DOI: 10.1016/j.celrep.2016.02.045
  2. Gupta SK, Kizilbash SH, Carlson BL, Mladek AC, Boakye-Agyeman F, Bakken KK, Pokorny JL, Schroeder MA, Decker PA, Cen L, Eckel-Passow JE, Sarkar G, Ballman KV, Reid JM, Jenkins RB, Verhaak RG, Sulman EP, Kitange GJ, Sarkaria JN. Delineation of MGMT Hypermethylation as a Biomarker for Veliparib-Mediated Temozolomide-Sensitizing Therapy of Glioblastoma. J Natl Cancer Inst. 2016 May; 108 (5) Epub 2015 Nov 27 PMID: 26615020 PMCID: 4862419   DOI: 10.1093/jnci/djv369
  3. Nagel ZD, Kitange GJ, Gupta SK, Joughin BA, Chaim IA, Mazzucato P, Lauffenburger DA, Sarkaria JN, Samson LD. DNA Repair Capacity in Multiple Pathways Predicts Chemoresistance in Glioblastoma Multiforme. Cancer Res. 2017 Jan 1; 77 (1):198-206 Epub 2016 Oct 28 PMID: 27793847 PMCID: 6100738   DOI: 10.1158/0008-5472.CAN-16-1151
    32.Ida CM, Butz ML, Jenkins RB, Sarkaria JN, Kitange GJ, Giannini C, Kipp BR.  Real-Time Methylation-Specific Polymerase Chain Reaction for MGMT Promoter Methylation Clinical Testing in Glioblastoma: An Alternative Detection Method for a Heterogeneous Process. Am J Clin Pathol. 2017 Oct 1; 148 (4):296-307 PMID: 28967952   DOI: 10.1093/ajcp/aqx073
  4. Kizilbash SH, Gupta SK, Chang K, Kawashima R, Parrish KE, Carlson BL, Bakken KK, Mladek AC, Schroeder MA, Decker PA, Kitange GJ, Shen Y, Feng Y, Protter AA, Elmquist WF, Sarkaria JN. Restricted Delivery of Talazoparib Across the Blood-Brain Barrier Limits the Sensitizing Effects of PARP Inhibition on Temozolomide Therapy in Glioblastoma. Mol Cancer Ther. 2017 Dec; 16 (12):2735-2746 Epub 2017 Sept 25 PMID: 28947502 PMCID: 5716902   DOI: 10.1158/1535-7163.MCT-17-0365
  5. Gupta SK, Smith EJ, Mladek AC, Tian S, Decker PA, Kizilbash SH, Kitange GJ, Sarkaria JN.  PARP Inhibitors for Sensitization of Alkylation Chemotherapy in Glioblastoma: Impact of Blood-Brain Barrier and Molecular Heterogeneity. Front Oncol. 2018; 8:670 Epub 2019 Jan 22 PMID: 30723695   PMCID: 6349736   DOI: 10.3389/fonc.2018.00670
  6. Chen X, Zhang M, Gan H, Wang H, Lee JH, Fang D, Kitange GJ, He L, Hu Z, Parney IF, Meyer FB, Giannini C, Sarkaria JN, Zhang Z. A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma. Nat Commun. 2018 Jul 27; 9 (1):2949 Epub 2018 July 27 PMID: 30054476 PMCID: 6063898   DOI: 10.1038/s41467-018-05373-4
  7. Kim M, Ma DJ, Calligaris D, Zhang S, Feathers RW, Vaubel RA, Meaux I, Mladek AC, Parrish KE, Jin F, Barriere C, Debussche L, Watters J, Tian S, Decker PA, Eckel-Passow JE, Kitange GJ, Johnson AJ, Parney IF, Anastasiadis PZ, Agar NYR, Elmquist WF, Sarkaria JN. Efficacy of the MDM2 Inhibitor SAR405838 in Glioblastoma Is Limited by Poor Distribution Across the Blood-Brain Barrier. Mol Cancer Ther. 2018 Sep; 17 (9):1893-1901 Epub 2018 July 03 PMID: 29970480 PMCID: 6125211   DOI: 10.1158/1535-7163.MCT-17-0600
  8. Nagel ZD, Beharry AA, Mazzucato P, Kitange GJ, Sarkaria JN, Kool ET, Samson LD. Fluorescent reporter assays provide direct, accurate, quantitative measurements of MGMT status in human cells. PLoS One. 2019; 14 (2):e0208341 Epub 2019 Feb 27 PMID: 30811507 PMCID: 6392231   DOI: 10.1371/journal.pone.0208341
  9. Burgenske DM, Yang J, Decker PA, Kollmeyer TM, Kosel ML, Mladek AC, Caron AA, Vaubel RA, Gupta SK, Kitange GJ, Sicotte H, Youland RS, Remonde D, Voss JS, Fritcher EGB, Kolsky KL, Ida CM, Meyer FB, Lachance DH, Parney IJ, Kipp BR, Giannini C, Sulman EP, Jenkins RB, Eckel-Passow JE, Sarkaria JN. Molecular profiling of long-term IDH-wildtype glioblastoma survivors. Neuro Oncol. 2019 Nov 4; 21 (11):1458-1469 PMID: 31346613 PMCID: 6827834   DOI: 10.1093/neuonc/noz129
  10. Harder BG, Peng S, Sereduk CP, Sodoma AM, Kitange GJ, Loftus JC, Sarkaria JN, Tran NL. Inhibition of phosphatidylinositol 3-kinase by PX-866 suppresses temozolomide-induced autophagy and promotes apoptosis in glioblastoma cells. Mol Med. 2019 Nov 14; 25 (1):49 PMID: 31726966 PMCID: 6854621   DOI: 10.1186/s10020-019-0116-z
  11. Vaubel RA, Tian S, Remonde D, Schroeder MA, Mladek AC, Kitange GJ, Caron A, Kollmeyer TM, Grove R, Peng S, Carlson BL, Ma DJ, Sarkar G, Evers L, Decker PA, Yan H, Dhruv HD, Berens ME, Wang Q, Marin BM, Klee EW, Califano A, LaChance DH, Eckel-Passow JE, Verhaak RG, Sulman EP, Burns TC, Meyer FB, O’Neill BP, Tran NL, Giannini C, Jenkins RB, Parney IF, Sarkaria JN. Genomic and Phenotypic Characterization of a Broad Panel of Patient-Derived Xenografts Reflects the Diversity of Glioblastoma. Clin Cancer Res. 2020 Mar 1; 26 (5):1094-1104 Epub 2019 Dec 18 PMID: 31852831 PMCID: 7056576   DOI: 10.1158/1078-0432.CCR-19-0909
  12. Eckel-Passow JE, Kitange GJ, Decker PA, Kosel ML, Burgenske DM, Oberg AL, Sarkaria JN. Experimental design of preclinical experiments: number of PDX lines vs subsampling within PDX lines. Neuro Oncol. 2021 Dec 1;23(12):2066-2075. doi: 10.1093/neuonc/noab137. PubMed PMID: 34107029; PubMed Central PMCID: PMC8643474.
  13. Marin BM, Porath KA, Jain S, Kim M, Conage-Pough JE, Oh JH, Miller CL, Talele S, Kitange GJ, Tian S, Burgenske DM, Mladek AC, Gupta SK, Decker PA, McMinn MH, Stopka SA, Regan MS, He L, Carlson BL, Bakken K, Burns TC, Parney IF, Giannini C, Agar NYR, Eckel-Passow JE, Cochran JR, Elmquist WF, Vaubel RA, White FM, Sarkaria JN. Heterogeneous delivery across the blood-brain barrier limits the efficacy of an EGFR-targeting antibody drug conjugate in glioblastoma. Neuro Oncol. 2021 Dec 1;23(12):2042-2053. doi: 10.1093/neuonc/noab133. PubMed PMID: 34050676; PubMed Central PMCID: PMC8643472.
  14. Burgenske DM, Talele S, Pokorny JL, Mladek AC, Bakken KK, Carlson BL, Schroeder MA, He L, Hu Z, Gampa G, Kosel ML, Decker PA, Kitange GJ, Schmitt-Hoffmann A, Bachmann F, Vaubel RA, Eckel-Passow JE, Giannini C, McSheehy P, Lane HA, Elmquist WF, Sarkaria JN. Preclinical modeling in GBM PDX xenografts to guide clinical development of lisavanbulin – a novel tumor checkpoint controller targeting microtubules. Neuro Oncol. 2021 Jul 7;. doi: 10.1093/neuonc/noab162. [Epub ahead of print] PubMed PMID: 34232318.

Additional publications: https://www.ncbi.nlm.nih.gov/myncbi/14IaqwoD2LqQu/bibliography/public/

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