Honors & Awards


  • Early Investigator Award, Department of Defense, CDMRP, Prostate Cancer Research Program (Aug 2018-July 2020)
  • Helena Anna Henzl-Gabor Young Women in Science Fund Travel Award for Postdoctoral Scholars, Stanford University (April 2017)
  • Research Mentor, Summer Research Academy, University of Central Florida (2010)
  • Summer Research Fellowship, American Cancer Society (2010)
  • Student Travel Award, Dr. Sidney A. McNair, Jr. Student Symposium, Clark Atlanta University, 10th Annual Prostate Cancer Symposium (2014)
  • Predoctoral Fellowship, Department of Defense (2014-2015)

Boards, Advisory Committees, Professional Organizations


  • Member, Society of Basic Urologic Research (2015 - Present)

Professional Education


  • Bachelor of Science, University of Central Florida (2009)
  • Doctor of Philosophy, University of Miami (2016)

Stanford Advisors


Community and International Work


  • Skype a Scientist

    Topic

    Outreach to students

    Populations Served

    Underserved youth in STEM

    Location

    International

    Ongoing Project

    Yes

    Opportunities for Student Involvement

    Yes

Lab Affiliations


All Publications


  • Second-Generation Antiandrogens: From Discovery to Standard of Care in Castration Resistant Prostate Cancer FRONTIERS IN ONCOLOGY Rice, M. A., Malhotra, S., Stoyanova, T. 2019; 9
  • Loss of Notch1 Activity Inhibits Prostate Cancer Growth and Metastasis and Sensitizes Prostate Cancer Cells to Antiandrogen Therapies MOLECULAR CANCER THERAPEUTICS Rice, M. A., Hsu, E., Aslan, M., Ghoochani, A., Su, A., Stoyanova, T. 2019; 18 (7): 1230–42
  • Arginine vasopressin receptor 1a is a therapeutic target for castration-resistant prostate cancer. Science translational medicine Zhao, N., Peacock, S. O., Lo, C. H., Heidman, L. M., Rice, M. A., Fahrenholtz, C. D., Greene, A. M., Magani, F., Copello, V. A., Martinez, M. J., Zhang, Y., Daaka, Y., Lynch, C. C., Burnstein, K. L. 2019; 11 (498)

    Abstract

    Castration-resistant prostate cancer (CRPC) recurs after androgen deprivation therapy (ADT) and is incurable. Reactivation of androgen receptor (AR) signaling in the low androgen environment of ADT drives CRPC. This AR activity occurs through a variety of mechanisms, including up-regulation of AR coactivators such as VAV3 and expression of constitutively active AR variants such as the clinically relevant AR-V7. AR-V7 lacks a ligand-binding domain and is linked to poor prognosis. We previously showed that VAV3 enhances AR-V7 activity to drive CRPC progression. Gene expression profiling after depletion of either VAV3 or AR-V7 in CRPC cells revealed arginine vasopressin receptor 1a (AVPR1A) as the most commonly down-regulated gene, indicating that this G protein-coupled receptor may be critical for CRPC. Analysis of publicly available human PC datasets showed that AVPR1A has a higher copy number and increased amounts of mRNA in advanced PC. Depletion of AVPR1A in CRPC cells resulted in decreased cell proliferation and reduced cyclin A. In contrast, androgen-dependent PC, AR-negative PC, or nontumorigenic prostate epithelial cells, which have undetectable AVPR1A mRNA, were minimally affected by AVPR1A depletion. Ectopic expression of AVPR1A in androgen-dependent PC cells conferred castration resistance in vitro and in vivo. Furthermore, treatment of CRPC cells with the AVPR1A ligand, arginine vasopressin (AVP), activated ERK and CREB, known promoters of PC progression. A clinically safe and selective AVPR1A antagonist, relcovaptan, prevented CRPC emergence and decreased CRPC orthotopic and bone metastatic growth in mouse models. Based on these preclinical findings, repurposing AVPR1A antagonists is a promising therapeutic approach for CRPC.

    View details for DOI 10.1126/scitranslmed.aaw4636

    View details for PubMedID 31243151

  • Loss of Notch1 activity inhibits prostate cancer growth and metastasis and sensitizes prostate cancer cells to anti-androgen therapies. Molecular cancer therapeutics Rice, M. A., Hsu, E. C., Aslan, M., Ghoochani, A., Su, A., Stoyanova, T. 2019

    Abstract

    Prostate cancer remains among the leading causes of cancer-related deaths in men. Patients with aggressive disease typically undergo hormone-deprivation therapy. While treatment is initially very successful, these men commonly progress to lethal, castration resistant prostate cancer in 2-3 years. Standard therapies for castration resistant prostate cancer include second-generation anti-androgens, which prolong patient lifespan by only several months. It is imperative to advance our understanding of the mechanisms leading to resistance to identify new therapies for aggressive prostate cancer. This study identifies Notch1 as a therapeutic target in prostate cancer. Loss of Notch1 in aggressive prostate cancer cells decreases proliferation, invasion and tumorsphere formation. Therapeutic inhibition of Notch1 activity with gamma secretase inhibitors RO4929097 or DAPT in prostate cancer cells further results in decreased proliferative abilities. Loss of Notch1 and treatment of immunocompromised mice bearing prostate cancer xenografts with RO4929097 display significantly impaired tumor growth. Loss of Notch1 additionally decreased metastatic potential of prostate cancer cells in invasion assays in vitro as well as in vivo experiments. Moreover, treatment with gamma secretase inhibitors, or Notch1 gene deletion synergized with anti-androgen therapies, Enzalutamide or Abiraterone, to decrease the growth of prostate cancer cells. Combination of gamma secretase inhibitors with Abiraterone significantly inhibited cell migration and invasion, while combination with Enzalutamide reversed Enzalutamide induced migration and invasion. These collective findings suggest loss of Notch1 delays growth of CRPC, inhibits metastasis, and inhibition of Notch1 activation in conjunction with second-generation anti-androgen therapies could delay growth and progression of prostate cancer.

    View details for PubMedID 31028097

  • Quantitative Proteomic Profiling Reveals Key Pathways in the Anticancer Action of Methoxychalcone Derivatives in Triple Negative Breast Cancer. Journal of proteome research Going, C. C., Tailor, D., Kumar, V., Birk, A. M., Pandrala, M., Rice, M. A., Stoyanova, T., Malhotra, S., Pitteri, S. J. 2018

    Abstract

    Triple negative breast cancer is an aggressive, heterogeneous disease with high recurrence and metastasis rates even with modern chemotherapy regimens and thus is in need of new therapeutics. Here, three novel synthetic analogues of chalcones, plant-based molecules that have demonstrated potency against a wide variety of cancers, were investigated as potential therapeutics for triple negative breast cancer. These compounds exhibit IC50 values of 5 muM in triple negative breast cancer cell lines and are more potent against triple negative breast cancer cell lines than against nontumor breast cell lines according to viability experiments. Tandem mass tag-based quantitative proteomics followed by gene set enrichment analysis and validation experiments using flow cytometry, apoptosis, and Western blot assays revealed three different anticancer mechanisms for these compounds. First, the chalcone analogues induce the unfolded protein response followed by apoptosis. Second, increases in the abundances of MHC-I pathway proteins occurs, which would likely result in immune stimulation in an organism. And third, treatment with the chalcone analogues causes disruption of the cell cycle by interfering with microtubule structure and by inducing G1 phase arrest. These data demonstrate the potential of these novel chalcone derivatives as treatments for triple negative breast cancer, though further work evaluating their efficacy in vivo is needed.

    View details for PubMedID 30200768

  • Defining new drivers of castration- resistant prostate cancer Hsu, E., Rice, M., Nolley, R., Bermudez, A., Huang, J., Peehl, D., Kunder, C., Pitteri, S., Brooks, J., Stoyanova, T. AMER ASSOC CANCER RESEARCH. 2018: 90
  • Methionine aminopeptidase II (MetAP2) activated in situ self-assembly of small-molecule probes for imaging prostate cancer. Xie, J., Rice, M., Cheng, Y., Song, G., Kunder, C., Brooks, J. D., Stoyanova, T., Rao, J. AMER ASSOC CANCER RESEARCH. 2018: 115–16
  • Targeting AR Variant-Coactivator Interactions to Exploit Prostate Cancer Vulnerabilities. Molecular cancer research : MCR Magani, F., Peacock, S. O., Rice, M. A., Martinez, M. J., Greene, A. M., Magani, P. S., Lyles, R., Weitz, J. R., Burnstein, K. L. 2017; 15 (11): 1469–80

    Abstract

    Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced prostate cancer. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC. Using mutational and biochemical studies, we demonstrated that the Vav3 Diffuse B-cell lymphoma homology (DH) domain interacted with the N-terminal region of AR-V7 (and full length AR). Expression of the Vav3 DH domain disrupted Vav3 interaction with and enhancement of AR-V7 activity. The Vav3 DH domain also disrupted AR-V7 interaction with other AR coactivators: Src1 and Vav2, which are overexpressed in PC. This Vav3 domain was used in proof-of-concept studies to evaluate the effects of disrupting the interaction between AR-V7 and its coactivators on CRPC cells. This disruption decreased CRPC cell proliferation and anchorage-independent growth, caused increased apoptosis, decreased migration, and resulted in the acquisition of morphological changes associated with a less aggressive phenotype. While disrupting the interaction between FL-AR and its coactivators decreased N-C terminal interaction, disrupting the interaction of AR-V7 with its coactivators decreased AR-V7 nuclear levels.Implications: This study demonstrates the potential therapeutic utility of inhibiting constitutively active AR-V signaling by disrupting coactivator binding. Such an approach is significant, as AR-Vs are emerging as important drivers of CRPC that are particularly recalcitrant to current therapies. Mol Cancer Res; 15(11); 1469-80. ©2017 AACR.

    View details for DOI 10.1158/1541-7786.MCR-17-0280

    View details for PubMedID 28811363

    View details for PubMedCentralID PMC5770277

  • Activation of Notch1 synergizes with multiple pathways in promoting castration-resistant prostate cancer PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Stoyanova, T., Riedinger, M., Lin, S., Faltermeier, C. M., Smith, B. A., Zhang, K. X., Going, C. C., Goldstein, A. S., Lee, J. K., Drake, J. M., Rice, M. A., Hsu, E., Nowroozizadeh, B., Castor, B., Orellana, S. Y., Blum, S. M., Cheng, D., Pienta, K. J., Reiter, R. E., Pitteri, S. J., Huang, J., Witte, O. N. 2016; 113 (42): E6457-E6466

    Abstract

    Metastatic castration-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-specific mortality. Defining new mechanisms that can predict recurrence and drive lethal CRPC is critical. Here, we demonstrate that localized high-risk prostate cancer and metastatic CRPC, but not benign prostate tissues or low/intermediate-risk prostate cancer, express high levels of nuclear Notch homolog 1, translocation-associated (Notch1) receptor intracellular domain. Chronic activation of Notch1 synergizes with multiple oncogenic pathways altered in early disease to promote the development of prostate adenocarcinoma. These tumors display features of epithelial-to-mesenchymal transition, a cellular state associated with increased tumor aggressiveness. Consistent with its activation in clinical CRPC, tumors driven by Notch1 intracellular domain in combination with multiple pathways altered in prostate cancer are metastatic and resistant to androgen deprivation. Our study provides functional evidence that the Notch1 signaling axis synergizes with alternative pathways in promoting metastatic CRPC and may represent a new therapeutic target for advanced prostate cancer.

    View details for DOI 10.1073/pnas.1614529113

    View details for PubMedID 27694579

  • The microRNA-23b/-27b cluster suppresses prostate cancer metastasis via Huntingtin-interacting protein 1-related. Oncogene Rice, M. A., Ishteiwy, R. A., Magani, F., Udayakumar, T., Reiner, T., Yates, T. J., Miller, P., Perez-Stable, C., Rai, P., Verdun, R., Dykxhoorn, D. M., Burnstein, K. L. 2016

    Abstract

    Deregulation of microRNAs (miRs) contributes to progression and metastasis of prostate and other cancers. miR-23b and -27b, encoded in the same miR cluster (miR-23b/-27b), are downregulated in human metastatic prostate cancer compared with primary tumors and benign tissue. Expression of miR-23b/-27b decreases prostate cancer cell migration, invasion and results in anoikis resistance. Conversely, antagomiR-mediated miR-23b and -27b silencing produces the opposite result in a more indolent prostate cancer cell line. However, neither miR-23b/-27b expression or inhibition impacts prostate cancer cell proliferation suggesting that miR-23b/-27b selectively suppresses metastasis. To examine the effects of miR-23b/-27b on prostate cancer metastasis in vivo, orthotopic prostate xenografts were established using aggressive prostate cancer cells transduced with miR-23b/-27b or non-targeting control miRNA. Although primary tumor formation was similar between miR-23b/-27b-transduced cells and controls, miR-23b/-27b expression in prostate cancer cells decreased seminal vesicle invasion and distant metastases. Gene-expression profiling identified the endocytic adaptor, Huntingtin-interacting protein 1-related (HIP1R) as being downregulated by miR-23b/-27b. Increased HIP1R expression in prostate cancer cells inversely phenocopied the effects of miR-23b/-27b overexpression on migration, invasion and anchorage-independent growth. HIP1R rescued miR-23b/-27b-mediated repression of migration in prostate cancer cells. HIP1R mRNA levels were decreased in seminal vesicle tissue from mice bearing miR-23b/-27b-transduced prostate cancer cell xenografts compared with scrambled controls, suggesting HIP1R is a key functional target of miR-23b/-27b. In addition, depletion of HIP1R led to a more rounded, less mesenchymal-like cell morphology, consistent with decreased metastatic properties. Together, these data demonstrate that the miR-23b/-27b cluster functions as a metastasis-suppressor by decreasing HIP1R levels in pre-clinical models of prostate cancer.Oncogene advance online publication, 22 February 2016; doi:10.1038/onc.2016.6.

    View details for DOI 10.1038/onc.2016.6

    View details for PubMedID 26898757

  • NACK Is an Integral Component of the Notch Transcriptional Activation Complex and Is Critical for Development and Tumorigenesis CANCER RESEARCH Weaver, K. L., Alves-Guerra, M., Jin, K., Wang, Z., Han, X., Ranganathan, P., Zhu, X., DaSilva, T., Liu, W., Ratti, F., Dennarest, R. M., Tzinnas, C., Rice, M., Vasquez-Del Carpio, R., Dahmane, N., Robbins, D. J., Capobianco, A. J. 2014; 74 (17): 4741-4751

    Abstract

    The Notch signaling pathway governs many distinct cellular processes by regulating transcriptional programs. The transcriptional response initiated by Notch is highly cell context dependent, indicating that multiple factors influence Notch target gene selection and activity. However, the mechanism by which Notch drives target gene transcription is not well understood. Herein, we identify and characterize a novel Notch-interacting protein, Notch activation complex kinase (NACK), which acts as a Notch transcriptional coactivator. We show that NACK associates with the Notch transcriptional activation complex on DNA, mediates Notch transcriptional activity, and is required for Notch-mediated tumorigenesis. We demonstrate that Notch1 and NACK are coexpressed during mouse development and that homozygous loss of NACK is embryonic lethal. Finally, we show that NACK is also a Notch target gene, establishing a feed-forward loop. Thus, our data indicate that NACK is a key component of the Notch transcriptional complex and is an essential regulator of Notch-mediated tumorigenesis and development.

    View details for DOI 10.1158/0008-5472.CAN-14-1547

    View details for Web of Science ID 000341833300018

    View details for PubMedID 25038227

    View details for PubMedCentralID PMC4154994