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Bitler Lab


Left to to right (top row): Levi Watson, Jaidev Bapat, Ben Bitler, Peggy Neville, Kian Behbakht, Christina Looby (bottom row): Patricia Webb, Tomomi Yamamoto, Lubna Qamar, Marisa Moroney, Allie McMellen

Drug resistant ovarian cancer is a major clinical challenge.  In the Bitler lab our goal is to better understand resistance mechanisms to both traditional and emerging ovarian cancer therapies.  Our group has two primary areas of research devoted to this goal.  In the context of drug resistant ovarian cancer we aim to: 1) examine the role of the Wnt/non-homologous end-joining signaling axis and 2) assess the impact of aberrant epigenetic regulation.  Our ultimate research objectives are to aid in the discovery and optimization of novel anti-ovarian cancer therapeutics.​​

 

 Bitler Lab

 
Bitler Lab:

​Benjamin Bitler, PhD: Principal Investigator
Levi Watson, PhD: Research Instructor
Allie McMellen: Cancer Biology Graduate Student
Jaidev Bapat: Cancer Biology Graduate Student
Tomomi Yamamoto, PhD: Research Associate
Elizabeth Woodruff: Professional Research Assistant
Marisa Moroney, MD: Gynecologic Oncology Fellow

Neville Lab:

Peggy Neville, PhD: Professor Emeritus
Patti Webb: Professional Research Assistant

1.     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 Mar 20. pii: molcanres.1057.2019. doi: 10.1158/1541-7786.MCR-19-1057. [Epub ahead of print]. PMID: 32198139


2.     Watson ZL, Yamamoto TM, McMellen A, Kim H, Hughes CJ, Wheeler LJ, Post MD, Behbakht K, Bitler BG. Histone methyltransferases EHMT1 and EHMT2 (GLP/G9A) maintain PARP inhibitor resistance in high-grade serous ovarian carcinoma. Clin Epigenetics. 2019 Nov 27;11(1):165. doi: 10.1186/s13148-019-0758-2. PMID: 31775874

3.     Rao DM, Shackleford MT, Bordeaux EK, Sottnik JL, Ferguson RL, Yamamoto TM, Wellberg EA, Bitler BG, Sikora MJ. Wnt family member 4 (WNT4) and WNT3A activate cell-autonomous Wnt signaling independent of porcupine O-acyltransferase or Wnt secretion. J Biol Chem. 2019 Dec 27;294(52):19950-19966. doi: 10.1074/jbc.RA119.009615. Epub 2019 Nov 18. PMID: 31740580

4.     Smith LP, Bitler BG, Richer JK, Christenson JL. Tryptophan catabolism in epithelial ovarian carcinoma. Trends Cancer Res. 2019;14:1-9. PMID: 31736606

5.     Park PH, Yamamoto TM, Li H, Alcivar AL, Xia B, Wang Y, Bernhardy AJ, Turner KM, Kossenkov AV, Watson ZL, Behbakht K, Casadei S, Swisher EM, Mischel PS, Johnson N, Bitler BG. Amplification of the Mutation-Carrying BRCA2 Allele Promotes RAD51 Loading and PARP Inhibitor Resistance in the Absence of Reversion Mutations. Mol Cancer Ther. 2020 Feb;19(2):602-613. doi: 10.1158/1535-7163.MCT-17-0256. Epub 2019 Oct 1. PMID: 31575654

6.     Wheeler LJ, Watson ZL, Qamar L, Yamamoto TM, Sawyer BT, Sullivan KD, Khanal S, Joshi M, Ferchaud-Roucher V, Smith H, Vanderlinden LA, Brubaker SW, Caino CM, Kim H, Espinosa JM, Richer JK, Bitler BG. Multi-Omic Approaches Identify Metabolic and Autophagy Regulators Important in Ovarian Cancer Dissemination. iScience. 2019 Sep 27;19:474-491. doi: 10.1016/j.isci.2019.07.049. Epub 2019 Aug 6. PMID: 31437751

7.     Ramzan AA, Bitler BG, Hicks D, Barner K, Qamar L, Behbakht K, Powell T, Jansson T, Wilson H. Adiponectin receptor agonist AdipoRon induces apoptotic cell death and suppresses proliferation in human ovarian cancer cells. Mol Cell Biochem. 2019 Nov;461(1-2):37-46. doi: 10.1007/s11010-019-03586-9. Epub 2019 Jul 10. PMID: 31292831

8.     Yamamoto TM, McMellen A, Watson ZL, Aguilera J, Ferguson R, Nurmemmedov E, Thakar T, Moldovan GL, Kim H, Cittelly DM, Joglar AM, Brennecke EP, Wilson H, Behbakht K, Sikora MJ, Bitler BG. Activation of Wnt signaling promotes olaparib resistant ovarian cancer. Mol Carcinog. 2019 Jun 10. doi: 10.1002/mc.23064. [Epub ahead of print] PubMed PMID: 31219654.

9.     Dahl ES, Buj R, Leon KE, Newell JM, Imamura Y, Bitler BG, Snyder NW, Aird KM. Targeting IDH1 as a Prosenescent Therapy in High-grade Serous Ovarian Cancer. Mol Cancer Res. 2019 May 20. doi: 10.1158/1541-7786.MCR-18-1233. [Epub ahead of print] PubMed PMID: 31110157.

10.  Breed C, Hicks DA, Webb PG, Galimanis CE, Bitler BG, Behbakht K, Baumgartner HK. Ovarian Tumor Cell Expression of Claudin-4 Reduces Apoptotic Response to Paclitaxel. Mol Cancer Res. 2019 Mar;17(3):741-750. doi: 10.1158/1541-7786.MCR-18-0451. Epub 2019 Jan 3. PubMed PMID: 30606772.

11.  Watson ZL, Bitler BG. Type I Protein Arginine Methyltransferases Overexpression Promotes Transformation and Potentiates Her2/Neu-Driven Tumorigenesis. Cancer Res. 2019 Jan 1;79(1):3-4. doi: 10.1158/0008-5472.CAN-18-3552. PubMed PMID: 30602621.

12.  Fukumoto T, Zhang R, Bitler BG. Epigenetic inhibitors for the precision treatment of ARID1A-mutant ovarian cancers: what are the next steps? Expert Rev Precis Med Drug Dev. 2018;3(4):233-236. doi: 10.1080/23808993.2018.1503050. Epub 2018 Jul 25. PubMed PMID: 30525111; PubMed Central PMCID: PMC6277026.

13.  Wheeler LJ, Watson ZL, Qamar L, Yamamoto TM, Post MD, Berning AA, Spillman MA, Behbakht K, Bitler BG. CBX2 identified as driver of anoikis escape and dissemination in high grade serous ovarian cancer. Oncogenesis. 2018 Nov26;7(11):92. doi: 10.1038/s41389-018-0103-1. PubMed PMID: 30478317; PubMed Central PMCID: PMC6255906.

14.  Fukumoto T, Park PH, Wu S, Fatkhutdinov N, Karakashev S, Nacarelli T, Kossenkov AV, Speicher DW, Jean S, Zhang L, Wang TL, Shih IM, Conejo-Garcia JR, Bitler BG, Zhang R. Repurposing Pan-HDAC Inhibitors for ARID1A-Mutated Ovarian Cancer. Cell Rep. 2018 Mar 27;22(13):3393-3400. doi: 10.1016/j.celrep.2018.03.019. PMID: 29590609 

15.  Karakashev S, Zhu H, Wu S, Yokoyama Y, Bitler BG, Park PH, Lee JH, Kossenkov AV, Gaonkar KS, Yan H, Drapkin R, Conejo-Garcia JR, Speicher DW, Ordog T, Zhang R. CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity. Nat Commun. 2018 Feb 12;9(1):631. doi: 10.1038/s41467-018-03031-3. PMID: 29434212 

16.  Karakashev S, Zhu H, Yokoyama Y, Zhao B, Fatkhutdinov N, Kossenkov AV, Wilson AJ, Simpkins F, Speicher D, Khabele D, Bitler BG, Zhang R. BET Bromodomain Inhibition Synergizes with PARP Inhibitor in Epithelial Ovarian Cancer. Cell Rep. 2017 Dec 19;21(12):3398-3405. doi: 10.1016/j.celrep.2017.11.095. PMID: 29262321

17.  Bitler BG, Watson ZL, Wheeler LJ, Behbakht K. PARP inhibitors: Clinical utility and possibilities of overcoming resistance. Gynecol Oncol. 2017 Dec;147(3):695-704. doi: 10.1016/j.ygyno.2017.10.003. Epub 2017 Oct 14. Review. PMID: 29037806

18.  Bitler BG, Wu S, et al. (2017). ARID1A-mutated ovarian cancers depend on HDAC6 activity. Nature Cell Biology. Aug;19(8):962-973. PMID: 28737768


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Agency: Department of Defense (OCRP-Pilot Award)

Title: Targeting Claudin-4 in PARP inhibitor resistant ovarian cancer

Project Period: 07/01/2018 - 06/30/2020

PIs: Benjamin Bitler and Tomomi Yamamoto

Agency: Cancer League Colorado (Research Grant)

Title: Investigating Histone Acetylation in PARP Inhibitor Resistant Ovarian Cancer 

Project Period: 07/01/2019 - 06/30/2020

PIs: Levi Watson

 

Agency: American Cancer Society Research Scholar Award

Title: Elucidating the role of Chromobox 2 in ovarian cancer progression

Project Period: 01/01/2020 – 12/31/2023

PI: Benjamin Bitler

 

Agency: University of Colorado Chancellor Fund                                                      

Title: Development of a CBX2 inhibitory peptide

PI: Benjamin Bitler and Lindsay Wheeler

Project Period: 02/01/2020-1/31/2021                                          

 

Agency: University of Colorado Cancer Center Developmental Therapeutics

Title: Collaborative Award: Modeling ovarian cancer in the presence of an immune system

Project period: 01/01/2020-12/31/2020

PI: Benjamin Bitler and Kian Behbakht


Agency: University of Colorado Cancer Center Developmental Therapeutics

Title: Mentored Member Pilot- Wnt/beta-catenin promotes immune evasion of chemoresistant ovarian cancer

Project period: 01/01/2020-12/31/2020

PI: Benjamin Bitler​

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