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Richer Lab


Contacts:

RC1 North  5th Floor P18-5127
Ph. 303 724-3735 office 303 724-3711 lab
 
Research Summary:  

The Richer lab examines mechanisms of resistance to current endocrine therapies and new endocrine therapy strategies. We study how non-coding RNAs affect differentiation state in the normal mammary gland and breast cancer, dictating cell and tissue specificity and timing of hormone receptor action including control of aspects of tumor metabolism and immune-suppression.

 
Areas of Current Research:

Our preclinical work on the androgen receptor (AR) in breast cancer led to ongoing clinical trials at our institution and others using anti-androgens for metastatic breast cancer. Another focus is on non-coding RNAs that control normal and oncogenic epithelial to mesenchymal transition and facilitate carcinoma metastasis. Recently we reported that restoration of miR-200c, termed the “guardian of the epithelial phenotype,” to TNBC revealed a mechanism whereby TNBC co-opt an immune suppressive program reminiscent of that used by fetal trophoblast to suppress the maternal immune system to ensure fetal tolerance during pregnancy.


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Recent Publications:

D’Amato NC, Rogers TJ, Gordon MA, Greene LI, Cochrane DR, Nemkov TG, Spoelstra NS, Hansen KC, and JK.Richer A TDO2-AhR Signaling axis is upregulated in suspension and regulates metastatic phenotypes in triple-negative breast cancer. CANCER RESEARCH 2015 Nov 1;75(21):4651-64 PMID: 26363006

Spoelstra NS, Cittelly DM, Christenson JL, Gordon MA, Elias A, Jedlicka P, and Richer JK. Evaluation of Dicer Expression in Estrogen Receptor alpha Positive versus Triple-Negative Breast Cancer: An Antibody Comparison. HUMAN PATHOLOGY. 2016. May 31. S0046-8177(16)30095-8

D’Amato NC, Jacobsen BM, Gordon MA, Babbs BL, Spoelstra NS, Carson Butterfield KT, Barton VN, Rogers TJ, Sartorius CA, Elias AD, Gertz, J and JK Richer.  Cooperative Dynamics of AR and ER Activity in Breast Cancer. MOLECULAR CANCER RESEARCH 2016 Nov;14(11):1054-1067. PMID: 27565181

Heinz RE, Rudolph MC, Ramanathan P, Spoelstra NS, Butterfield KT, Webb PG, Babbs BL, Gao H, Chen S, Gordon MA, Anderson SM, Neville MC, Gu H, Richer JK (2016). Constitutive expression of microRNA-150 in mammary epithelium suppresses secretory activation and impairs de novo lipogenesis. DEVELOPMENT 2016 Oct 11. PMID: 27729410

Christenson JL, Butterfield KT, Spoelstra NS, Norris JD, Josan JS, Pollock JA, McDonnell DP, Katzenellenbogen BS, Katzenellenbogen JA, and JK Richer. MMTV-PyMT and Derived Met-1 Mouse Mammary Tumor Cells as Models for Studying the Role of the Androgen Receptor in Triple-Negative Breast Cancer Progression. HORMONES AND CANCER. 2017 Apr;8(2):69-77.PMID: 28194662

Gordon MA, D'Amato NC , Gu H , Babbs B, Wulfkuhle JD , Petricoin EF, Gallagher RI, Dong T, Torkko KC, Liu B , Elias A and JK Richer Synergy between androgen receptor antagonism and inhibition of mTOR and HER2 in breast cancer. MOLECULAR CANCER THERAPEUTICS. 2017 Jul;16(7):1389-1400.  PMID: 28468774

Barton VN., Christenson JL, Rogers TJ, Butterfield K, Babbs B, Spoelstra NS, D’Amato NC, Elias A, and JK Richer. Androgen receptor supports an anchorage independent, cancer stem cell like population in triple negative breast cancer. CANCER RESEARCH. 2017 Jul 1;77(13):3455-3466. PMID: 28512248

Wellberg EA, Checkley LA, Giles ED, Johnson SJ, Oljira R, Wahdan-Alaswad R, Foright RM, Dooley G, Edgerton SM, Jindal S, Johnson GC, Richer JK, Kabos P, Thor AD, Schedin P, MacLean PS, Anderson SM. The Androgen Receptor Supports Tumor Progression After the Loss of Ovarian Function in a Preclinical Model of Obesity and Breast Cancer. HORMONES AND CANCER. 2017 Jul 24. PMID: 28741260.

Gordon MA, Babbs B, Cochrane DR, Bitler BG, JK Richer. The long non-coding RNA MALAT1 promotes ovarian cancer progression by regulating RBFOX2-mediated alternative splicing. MOL  CARCINOG 2018 Oct 8. PMID: 30294913

Rogers TJ, Christenson JL, Greene LI, O'Neill KI, Williams MM, Gordon MA, Nemkov T, D'Alessandro A, Degala GD, Shin J, Tan AC, Cittelly DM, Lambert JR, Richer JK. Reversal of Triple-Negative Breast Cancer EMT by miR-200c Decreases Tryptophan Catabolism and a Program of Immunosuppression. MOL CA RES 2019. Jan 17(1): 30-41. PMID: 30213797

Greene LI, Bruno TC, Christenson JL, D'Alessandro A, Culp-Hill R, Torkko K, Borges VF, Slansky JE, Richer JK.A Role for Tryptophan-2,3-dioxygenase in CD8 T-cell Suppression and Evidence of Tryptophan Catabolism in Breast Cancer Patient Plasma. MOL CA RES 2019 Jan 17(1):131-139. PMID: 30143553