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Isabel R Schlaepfer

TitleAsst Professor
InstitutionUniversity of Colorado Denver - Anschutz Medical Campus
DepartmentSOM-OB/GYN RS GENERAL OPS
Email

    Collapse Overview 
    Collapse overview
    The goal of my research is to elucidate how cancer cells use lipid to their benefit, leading to the design of more effective therapies. As a background, I worked as a lab tech in molecular and lipid metabolism for more than a decade while caring for my young family. In 2005 I started my doctoral studies in physiology and genetics at CU Boulder, under a NIDA pre-doctoral training grant. At the completion of my PhD, I returned to CU medical campus and obtained a 3-year ACS fellowship to initiate my training in cancer and lipid metabolism. This cancer training led me to secure a 5- year K01 award from NCI to continue my cancer research studies and to obtain a tenure-track faculty position in the Division of Medical Oncology. I am currently funded by an independent ACS research scholar grant to investigate the pharmacological inhibition of beta-oxidation and androgen receptor (AR) signaling. The research in my lab focuses on the molecular understanding of cancer lipid catabolism via CPT1A, a mitochondrial rate-limiting enzyme for beta-oxidation that I have found to be very abundant in prostate cancer. Specifically, I have developed effective measures of lipid catabolism in prostate cancer cells and tied these metabolic findings to hormonal (AR), biochemical and signaling pathways, using human and mouse models. This research has led to identification of novel non-toxic combinatorial therapies for advanced prostate cancer. Furthermore, the implications of my research go beyond prostate cancer, as breast, ovarian, colon and pancreatic cancers are very lipid-dependent as well, expanding the significance of my work.

    Collapse Research 
    Collapse research activities and funding
    K01CA168934     (SCHLAEPFER, ISABEL RUBIO)Sep 7, 2012 - Aug 31, 2018
    NIH
    Targeting Lipid Oxidation for Prostate Cancer Imaging and Therapy
    Role: Principal Investigator

    129846-RSG-16-256-01-TBE     (Isabel Schlaepfer)Jan 1, 2017 - Dec 31, 2020
    American Cancer Society
    CPT1A-mediated Fat Oxidation as a Therapeutic Target in Prostate Cancer
    Role Description: Study the therapeutic potential of targeting CPT1A and androgen receptor in prostate cancer
    Role: Principal Investigator

    AWD-193286     (Isabel R Schlaepfer)Jul 1, 2019 - Jun 30, 2020
    Cancer League of Colorado
    Role of fat oxidation via CPT1A in immunological response to prostate cancer
    Role Description: study the role of fat oxidation and T cell response in prostate cancer
    Role: Principal investigator

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Kim KN, Oh KS, Shim J, Schlaepfer IR, Karam SD, Lee JJ. Light-Responsive Polymeric Micellar Nanoparticles with Enhanced Formulation Stability. Polymers (Basel). 2021 Jan 26; 13(3). PMID: 33530388.
      View in: PubMed
    2. Guth A, Monk E, Agarwal R, Bergman BC, Zemski-Berry KA, Minic A, Jordan K, Schlaepfer IR. Targeting Fat Oxidation in Mouse Prostate Cancer Decreases Tumor Growth and Stimulates Anti-Cancer Immunity. Int J Mol Sci. 2020 Dec 18; 21(24). PMID: 33352903.
      View in: PubMed
    3. Joshi M, Kim J, D'Alessandro A, Monk E, Bruce K, Elajaili H, Nozik-Grayck E, Goodspeed A, Costello JC, Schlaepfer IR. CPT1A Over-Expression Increases Reactive Oxygen Species in the Mitochondria and Promotes Antioxidant Defenses in Prostate Cancer. Cancers (Basel). 2020 Nov 18; 12(11). PMID: 33218188.
      View in: PubMed
    4. Sawyer BT, Qamar L, Yamamoto TM, McMellen A, Watson ZL, Richer JK, Behbakht K, Schlaepfer IR, Bitler BG. Targeting Fatty Acid Oxidation to Promote Anoikis and Inhibit Ovarian Cancer Progression. Mol Cancer Res. 2020 07; 18(7):1088-1098. PMID: 32198139.
      View in: PubMed
    5. Schlaepfer IR, Joshi M. CPT1A-mediated Fat Oxidation, Mechanisms, and Therapeutic Potential. Endocrinology. 2020 02 01; 161(2). PMID: 31900483.
      View in: PubMed
    6. Paton EL, Turner JA, Schlaepfer IR. Overcoming Resistance to Therapies Targeting the MAPK Pathway in BRAF-Mutated Tumours. J Oncol. 2020; 2020:1079827. PMID: 32411231.
      View in: PubMed
    7. Joshi M, Stoykova GE, Salzmann-Sullivan M, Dzieciatkowska M, Liebman LN, Deep G, Schlaepfer IR. CPT1A Supports Castration-Resistant Prostate Cancer in Androgen-Deprived Conditions. Cells. 2019 09 20; 8(10). PMID: 31547059.
      View in: PubMed
    8. Stoykova GE, Schlaepfer IR. Lipid Metabolism and Endocrine Resistance in Prostate Cancer, and New Opportunities for Therapy. Int J Mol Sci. 2019 May 28; 20(11). PMID: 31142021.
      View in: PubMed
    9. Dheeraj A, Agarwal C, Schlaepfer IR, Raben D, Singh R, Agarwal R, Deep G. A novel approach to target hypoxic cancer cells via combining ß-oxidation inhibitor etomoxir with radiation. Hypoxia (Auckl). 2018; 6:23-33. PMID: 30175155.
      View in: PubMed
    10. Pathak GP, Shah R, Kennedy BE, Murphy JP, Clements D, Konda P, Giacomantonio M, Xu Z, Schlaepfer IR, Gujar S. RTN4 Knockdown Dysregulates the AKT Pathway, Destabilizes the Cytoskeleton, and Enhances Paclitaxel-Induced Cytotoxicity in Cancers. Mol Ther. 2018 08 01; 26(8):2019-2033. PMID: 30078441.
      View in: PubMed
    11. Peak TC, Praharaj PP, Panigrahi GK, Doyle M, Su Y, Schlaepfer IR, Singh R, Vander Griend DJ, Alickson J, Hemal A, Atala A, Deep G. Exosomes secreted by placental stem cells selectively inhibit growth of aggressive prostate cancer cells. Biochem Biophys Res Commun. 2018 05 23; 499(4):1004-1010. PMID: 29627574.
      View in: PubMed
    12. Yang X, Su LJ, La Rosa FG, Smith EE, Schlaepfer IR, Cho SK, Kavanagh B, Park W, Flaig TW. The Antineoplastic Activity of Photothermal Ablative Therapy with Targeted Gold Nanorods in an Orthotopic Urinary Bladder Cancer Model. Bladder Cancer. 2017 Jul 27; 3(3):201-210. PMID: 28824948.
      View in: PubMed
    13. Futia GL, Schlaepfer IR, Qamar L, Behbakht K, Gibson EA. Statistical performance of image cytometry for DNA, lipids, cytokeratin, & CD45 in a model system for circulation tumor cell detection. Cytometry A. 2017 07; 91(7):662-674. PMID: 28608985.
      View in: PubMed
    14. Flaig TW, Salzmann-Sullivan M, Su LJ, Zhang Z, Joshi M, Gijón MA, Kim J, Arcaroli JJ, Van Bokhoven A, Lucia MS, La Rosa FG, Schlaepfer IR. Lipid catabolism inhibition sensitizes prostate cancer cells to antiandrogen blockade. Oncotarget. 2017 Aug 22; 8(34):56051-56065. PMID: 28915573.
      View in: PubMed
    15. Mukhopadhyay S, Schlaepfer IR, Bergman BC, Panda PK, Praharaj PP, Naik PP, Agarwal R, Bhutia SK. ATG14 facilitated lipophagy in cancer cells induce ER stress mediated mitoptosis through a ROS dependent pathway. Free Radic Biol Med. 2017 03; 104:199-213. PMID: 28069524.
      View in: PubMed
    16. Deep G, Schlaepfer IR. Aberrant Lipid Metabolism Promotes Prostate Cancer: Role in Cell Survival under Hypoxia and Extracellular Vesicles Biogenesis. Int J Mol Sci. 2016 Jul 02; 17(7). PMID: 27384557.
      View in: PubMed
    17. Schlaepfer IR, Nambiar DK, Ramteke A, Kumar R, Dhar D, Agarwal C, Bergman B, Graner M, Maroni P, Singh RP, Agarwal R, Deep G. Hypoxia induces triglycerides accumulation in prostate cancer cells and extracellular vesicles supporting growth and invasiveness following reoxygenation. Oncotarget. 2015 Sep 08; 6(26):22836-56. PMID: 26087400.
      View in: PubMed
    18. Schlaepfer IR, Glodé LM, Hitz CA, Pac CT, Boyle KE, Maroni P, Deep G, Agarwal R, Lucia SM, Cramer SD, Serkova NJ, Eckel RH. Inhibition of Lipid Oxidation Increases Glucose Metabolism and Enhances 2-Deoxy-2-[(18)F]Fluoro-D-Glucose Uptake in Prostate Cancer Mouse Xenografts. Mol Imaging Biol. 2015 Aug; 17(4):529-38. PMID: 25561013.
      View in: PubMed
    19. Schlaepfer IR, Rider L, Rodrigues LU, Gijón MA, Pac CT, Romero L, Cimic A, Sirintrapun SJ, Glodé LM, Eckel RH, Cramer SD. Lipid catabolism via CPT1 as a therapeutic target for prostate cancer. . 2014 Oct; 13(10):2361-71. PMID: 25122071.
      View in: PubMed
    20. Potcoava MC, Futia GL, Aughenbaugh J, Schlaepfer IR, Gibson EA. Raman and coherent anti-Stokes Raman scattering microscopy studies of changes in lipid content and composition in hormone-treated breast and prostate cancer cells. J Biomed Opt. 2014; 19(11):111605. PMID: 24933682.
      View in: PubMed
    21. Schlaepfer IR, Hitz CA, Gijón MA, Bergman BC, Eckel RH, Jacobsen BM. Progestin modulates the lipid profile and sensitivity of breast cancer cells to docetaxel. Mol Cell Endocrinol. 2012 Nov 05; 363(1-2):111-21. PMID: 22922095.
      View in: PubMed
    22. Stephens SH, Hoft NR, Schlaepfer IR, Young SE, Corley RC, McQueen MB, Hopfer C, Crowley T, Stallings M, Hewitt J, Ehringer MA. Externalizing behaviors are associated with SNPs in the CHRNA5/CHRNA3/CHRNB4 gene cluster. Behav Genet. 2012 May; 42(3):402-14. PMID: 22042234.
      View in: PubMed
    23. Capell WH, Schlaepfer IR, Wolfe P, Watson PA, Bessesen DH, Pagliassotti MJ, Eckel RH. Fatty acids increase glucose uptake and metabolism in C2C12 myoblasts stably transfected with human lipoprotein lipase. Am J Physiol Endocrinol Metab. 2010 Oct; 299(4):E576-83. PMID: 20628023.
      View in: PubMed
    24. Hoft NR, Corley RP, McQueen MB, Schlaepfer IR, Huizinga D, Ehringer MA. Genetic association of the CHRNA6 and CHRNB3 genes with tobacco dependence in a nationally representative sample. Neuropsychopharmacology. 2009 Feb; 34(3):698-706. PMID: 18704094.
      View in: PubMed
    25. Schlaepfer IR, Hoft NR, Ehringer MA. The genetic components of alcohol and nicotine co-addiction: from genes to behavior. Curr Drug Abuse Rev. 2008 Jun; 1(2):124-34. PMID: 19492010.
      View in: PubMed
    26. Schlaepfer IR, Hoft NR, Collins AC, Corley RP, Hewitt JK, Hopfer CJ, Lessem JM, McQueen MB, Rhee SH, Ehringer MA. The CHRNA5/A3/B4 gene cluster variability as an important determinant of early alcohol and tobacco initiation in young adults. Biol Psychiatry. 2008 Jun 01; 63(11):1039-46. PMID: 18163978.
      View in: PubMed
    27. Zeiger JS, Haberstick BC, Schlaepfer I, Collins AC, Corley RP, Crowley TJ, Hewitt JK, Hopfer CJ, Lessem J, McQueen MB, Rhee SH, Ehringer MA. The neuronal nicotinic receptor subunit genes (CHRNA6 and CHRNB3) are associated with subjective responses to tobacco. Hum Mol Genet. 2008 Mar 01; 17(5):724-34. PMID: 18055561.
      View in: PubMed
    28. Ehringer MA, Clegg HV, Collins AC, Corley RP, Crowley T, Hewitt JK, Hopfer CJ, Krauter K, Lessem J, Rhee SH, Schlaepfer I, Smolen A, Stallings MC, Young SE, Zeiger JS. Association of the neuronal nicotinic receptor beta2 subunit gene (CHRNB2) with subjective responses to alcohol and nicotine. . 2007 Jul 05; 144B(5):596-604. PMID: 17226798.
      View in: PubMed
    29. Schlaepfer IR, Clegg HV, Corley RP, Crowley TJ, Hewitt JK, Hopfer CJ, Krauter K, Lessem J, Rhee SH, Stallings MC, Wehner JM, Young SE, Ehringer MA. The human protein kinase C gamma gene (PRKCG) as a susceptibility locus for behavioral disinhibition. Addict Biol. 2007 Jun; 12(2):200-9. PMID: 17508994.
      View in: PubMed
    30. Schlaepfer IR, Pulawa LK, Eckel RH. Cloning and characterization of Munc18c(L), a novel murine Munc18c gene paralog. Biochem Biophys Res Commun. 2005 Sep 02; 334(3):911-6. PMID: 16036223.
      View in: PubMed
    31. Schlaepfer IR, Pulawa LK, Ferreira LD, James DE, Capell WH, Eckel RH. Increased expression of the SNARE accessory protein Munc18c in lipid-mediated insulin resistance. J Lipid Res. 2003 Jun; 44(6):1174-81. PMID: 12700337.
      View in: PubMed
    32. Poirier P, Marcell T, Huey PU, Schlaepfer IR, Owens GC, Jensen DR, Eckel RH. Increased intracellular triglyceride in C(2)C(12) muscle cells transfected with human lipoprotein lipase. Biochem Biophys Res Commun. 2000 Apr 21; 270(3):997-1001. PMID: 10772940.
      View in: PubMed
    33. Schlaepfer IR, Eckel RH. Plasma triglyceride reduction in mice after direct injections of muscle-specific lipoprotein lipase DNA. Diabetes. 1999 Jan; 48(1):223-7. PMID: 9892249.
      View in: PubMed
    34. Jensen DR, Schlaepfer IR, Morin CL, Pennington DS, Marcell T, Ammon SM, Gutierrez-Hartmann A, Eckel RH. Prevention of diet-induced obesity in transgenic mice overexpressing skeletal muscle lipoprotein lipase. Am J Physiol. 1997 Aug; 273(2 Pt 2):R683-9. PMID: 9277555.
      View in: PubMed
    35. Eckel RH, Jensen DR, Schlaepfer IR, Yost TJ. Tissue-specific regulation of lipoprotein lipase by isoproterenol in normal-weight humans. Am J Physiol. 1996 Nov; 271(5 Pt 2):R1280-6. PMID: 8945965.
      View in: PubMed
    36. Morin CL, Schlaepfer IR, Eckel RH. Tumor necrosis factor-alpha eliminates binding of NF-Y and an octamer-binding protein to the lipoprotein lipase promoter in 3T3-L1 adipocytes. J Clin Invest. 1995 Apr; 95(4):1684-9. PMID: 7706477.
      View in: PubMed
    37. Schlaepfer IR, Mattoon JR, Bajszár G. The sequence and potential regulatory elements of the HEM2 promoter of Saccharomyces cerevisiae. Yeast. 1994 Feb; 10(2):227-9. PMID: 8203163.
      View in: PubMed
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