Resume

• 2017

  Faculty Representative

  College Diabetes Network

• 2011

  Poster Presentation at 2 Conferences/Meetings:\nCancer Research Symposium Poster

  University of Michigan Comprehensive Cancer Center

  Ann Arbor

  MI. Dec 17

  2010\nAACR Annual Meeting April 2-6

  Therapeutic targeting of the Notch pathway in breast cancer stem cells.

  Abstract\nThis study identified CD63

  a member of the tetraspanin family

  as a TIMP-1 interacting protein by yeast two-hybrid screening. Immunoprecipitation and confocal microscopic analysis confirmed CD63 interactions with TIMP-1

  integrin beta1

  and their co-localizations on the cell surface of human breast epithelial MCF10A cells. TIMP-1 expression correlated with the level of active integrin beta1 on the cell surface independent of cell adhesion. While MCF10A cells within a three-dimensional (3D) matrigel matrix form polarized acinar-like structures

  TIMP-1 overexpression disrupted breast epithelial cell polarization and inhibited caspase-mediated apoptosis in centrally located cells

  necessary for the formation and maintenance of the hollow acinar-like structures. Small hairpin RNA (shRNA)-mediated CD63 downregulation effectively reduced TIMP-1 binding to the cell surface

  TIMP-1 co-localization with integrin beta1

  and consequently reversed TIMP-1-mediated integrin beta1 activation

  cell survival signaling and apoptosis inhibition. CD63 downregulation also restored polarization and apoptosis of TIMP-1 overexpressing MCF10A cells within a 3D-matrigel matrix. Taken together

  the present study identified CD63 as a cell surface binding partner for TIMP-1

  regulating cell survival and polarization via TIMP-1 modulation of tetraspanin/integrin signaling complex.

  Identification of CD63 as a tissue inhibitor of metalloproteinase-1 interacting cell surface protein.

  Rosemarie

  Wayne State University School of Medicine

  Karmanos Cancer Institute

  University of Michigan - Research and Sponsored Projects

  National Science Foundation (NSF)

  Macomb Community College

  Marygrove College

  Oakland University

  PRECISIONscientia

  National Science Foundation Faculty Institutes for Reforming Science Teaching (FIRST IV) Fellowship

  •\tChosen to participate in a professional development program for postdoctoral fellows interested in learning the evidence-based research behind the science of teaching and learning and STEM education reform\n•\tAttended two

  all expenses paid summer workshops

  designed and taught a student-centered biology course in a cooperative group and received feedback on teaching experience

  Science of Teaching and Learning

  University of Michigan

• 2009

  Postdoctoral Fellow at Comprehensive Cancer Center

  Internal Medicine (Hematology/Oncology)

  University of Michigan

• 2007

  Member of Women in Cancer Group

  Associate Member

  American Association of Cancer Research

  Spanish

  Lilly Conference Travel Grant for Presentation of Oral Presentation

  Center for Teaching and Learning at Oakland University

  The DOD Era of Hope Meeting

  Poster Presentation

  Baltimore

  MD

  Department of Defense

  WSU School of Medicine Outstanding Graduate Student Award

  $500

  Wayne State University School of Medicine

  National Cancer Institute (NCI)

  Ruth L. Kirschstein National Research Service Award Institutional Research Training (T32) Fellowship

  $42

  000/year

  National Cancer Institute

  U.S. Army Medical Research and Materiel Command (USAMRMC)

  Department of Defense (DOD) Breast Cancer Research Program (BCRP) Predoctoral Traineeship Award

  $30

  000/year

  Department of Defense

  The Edward A. Smuckler Memorial Workshop: Pathobiology of Cancer (AACR) Workshop in Cancer Research

  Snowmass Village

  CO

  An intensive one-week course with gross and microscopic diagnostic training devoted to normal histology and cancer of the major organ systems including: (1) hematopoietic tissues (2) gastrointestinal tract; (3) childhood tumors and brain; (4) breast

  uterus

  cervix

  and ovary; (5) male genitourinary tract; and (6) lung and skin.

  American Association for Cancer Research

• 2006

  Student Representative for my program

  Student Member of Cancer Biology Curriculum Committee

  American Association for the Advancement of Science (AAAS)

• 2005

  Student Representative for Cancer Biology Program at Wayne State

• 2003

  Doctor of Philosophy - PhD

  Cancer Biology

  Wayne State University School of Medicine

  GPA 3.9

• 2001

  Master of Science - MS

  \n

  Basic Medical Sciences

  Wayne State University School of Medicine

  GPA 3.7

• 1996

  Bachelor of Science - BS

  Human Biology

  Michigan State University

  GPA 3.4

  Community Engaged Research Training

  Law

  Values

  and Healthcare (Bioethics)

  Human Genetics

  Introduction to Organic and Biochemistry

  Health in Personal and Occupational Enviornments

  Human Pathology

  Nutrient Metabolism

  Anatomy and Physiology

  LinkedIn

  Betty Liu on Career Success

  Jodi Glickman on Pitching Yourself

  LinkedIn

  Association of Clinical Research Professionals: Introduction to Clinical Research Webinar Training

  Giving Your Elevator Pitch

  LinkedIn

  NIDA Training in Good Clinical Practice Guidelines

  Negotiating Your Job Offer

  LinkedIn

  The Edward A. Smuckler Memorial Workshop: Pathobiology of Cancer (AACR) Workshop in Cancer Research

  Snowmass Village

  CO

• 500.

  Detroit

  MI

  Essay Advisors: Richard Everson

  M.D.

  M.P.H & James Eliason

  Ph.D.\nEssay Project: Using the Comet Assay to Observe DNA Damage of Breast Cancer Cells after Treatment with Chemotherapeutic Drugs\n\n•\tHigh collaboration skills working with the biotech company Asterand to separate out tumor cells from frozen bone marrow of patients that underwent chemotherapy to study resistance resulting in awarding of the WSU Graduate Student Fellowship

  $2

  Graduate Research Assistant M.S. in Basic Medical Sciences Program

  Karmanos Cancer Institute

  Kellogg Biological Research Station (Hickory Corners

  MI)

  NSF FIRST IV Fellowship

  Co-Principle Investigators of the NSF grant: Diane Ebert-May

  Ph.D. (Michigan State University

  East Lansing

  MI) &Terry Derting

  Ph.D. (Murray State University

  Murray

  KY \n•\tStrong development of professional skills after being chosen to participate in a competitive program for postdoctoral fellows interested in STEM education reform.\n•\tAttended two

  all expenses paid summer workshops

  designed and taught Human Genetics for the Molecular Cellular and Developmental Biology Department

  University of Michigan

  Ann Arbor

  MI (Summer 2011)

  and received feedback on teaching experience.

  Postdoctoral Teaching Fellow and Intermittent Lecturer

  National Science Foundation (NSF)

  Warren

  Michigan

  Arts and Sciences Department\nMacomb Community College South Campus\n\n•\tKnowledgeable curriculum designer and developer using backward design and learning outcomes for assessments and activities in an Introductory lecture and laboratory Biology course.\n•\tStrong leadership and technological skills resulting in being chosen as the first adjunct to teach Anatomy and Physiology using the Willey-Plus publisher web-based learning platform.

  Adjunct Professor

  Macomb Community College

  Precision Medicine Group Inc. acquired ETHOS Health Communications

  a Pennsylvania-based agency that specializes in the interpretation and communication of innovative medical science in 2018. ETHOS Health Communications is now known as PRECISIONscientia.

  PRECISIONscientia

  Wayne State University School of Medicine

  Detroit

  MI

  Graduate Research Assistant Cancer Biology Program\nDissertation Mentor: Hyeong-Reh Choi Kim

  Ph.D. \nDissertation Project: The Novel Functions of the Tissue Inhibitor of Metalloproteinase (TIMP-1): Inhibition of Apoptosis and Induction of an Epithelial-Mesenchymal Transition\n\n•\tExcellent science writer and collaborator contributing to NIH RO1 grants (1.9 million) and 2 first author and 2 contributing publications including an individual U.S. Army Department of Defense Breast Cancer Research Program Predoctoral Traineeship Award

  $30

  000/year.\n•\tExpertise in technical

  market-knowledge

  and problem-solving skills in molecular genetics and cellular biology techniques contributing to the design of established protocols in the laboratory.\n•\tHigh-level project management and leadership skills demonstrated by the training of students working in the laboratory resulting in summer fellowships and acceptance into medical school.\n•\tStrong communication skills resulting in winning of graduate student and Scholar in Training awards leading to invitations to present research at international (AACR) and local meetings.\n•\tStrong relationship builder with health care practitioners and KOLs while doing clinical rotations of oncologists at Karmanos Cancer Institute resulting in interest in translational cancer research.

  Project Manager and Medical Writer Experience

  Ann Arbor

  MI

  Postdoctoral Fellow\nUniversity of Michigan Comprehensive Cancer Center\nPrinciple Investigator: Max Wicha

  M.D.\nProjects: Activation and Tumorigenesis of Notch Stem Cell Pathway in Breast Cancer Cells and Identification of Cancer Stem Cell Biomarkers in Normal Mammary Tissue\n\n•\tExcellent teamwork and project management skills working on several multifaceted research projects resulting in two first author journal publications

  3 contributing author publications

  and \nNational Cancer Institute (NCI) Research Training (T32) Fellowship

  $42

  000/year.\no\tMember of the Stand Up to Cancer Dream Team resulting in the sharing of $73 million dollars towards new treatments from lab to cancer patient.\n•\tRelationship builder with Merck to conduct preclinical tumor imaging studies using cell lines and NOD/SCID mice for drug development of a Gamma Secretase Inhibitor (GSI) against the Notch pathway leading to establishment of new therapeutic combinations against breast cancer.\n•\tHigh-level technical and problem-solving skills demonstrated in the process of generating cells from reduction mammoplasties resulting in the development of complex multi-color flow cytometry biomarker protocols.\n•\tStrong leadership skills demonstrated in the teaching of daily research activities

  project development

  and writing of fellowship applications leading to specialized training of undergraduate students

  visiting medical fellows

  researchers

  and pathologists.\n•\tKnowledge of current industry trends and experience communicating complex topics to diverse audiences resulting in presentations at international meetings like AACR.

  Project Manager and Medical Writer Experience

  University of Michigan - Research and Sponsored Projects

  Detroit

  MI

  Science and Math Department\nMarygrove College\n\n•\tStrong team player and communicator working with other adjunct and full-time faculty leading to uniformity among assessments in 2 sections of an Introductory Biology course.\n•\tExcellent resource and time management skills responsible for the development and organization of all sections of Introductory Biology laboratories resulting in newer inquiry-based lab exercises.\n•\tStrong leadership skills resulting in being chosen as first adjunct to co-teach Introduction to Organic and Biochemistry

  focusing on the Biochemistry portion of the course.\n•\tCompetent technological skills utilizing online materials from McGraw Hill Connect websites for Biology and Biochemistry resulting in decreased assessment development and grading time.

  Adjunct Professor

  Marygrove College

  Rochester

  MI

  Interdisciplinary Health\nOakland University School of Health Sciences\n\n•\tHigh level educator with diverse teaching and curriculum development on the prevention

  management

  and treatment of diseases resulting in the training of Health Science students.\n•\tExcellent interdisciplinary collaboration skills demonstrated working in cross functional teams to design assessments and train 6 undergraduate student graders to maximize grading efficiency.\n•\tExpanded professional awareness and development in evidence-based learning in STEM fields including: flipping the classroom

  adult learning theory

  active and problem-based learning resulting in a learner-centered approach to teaching.\n•\tStrong project management skills in community research demonstrated by planning 5 individual and one large community class project for the Parks and Recreation Department of Pontiac

  MI.\n•\tPassionate presentation and communication skills demonstrated at oral sessions at local and national conferences including awarding of a travel grant to a Lilly teaching conference ($1

  200).

  Visiting Assistant Professor

  Oakland University

• 500

  WSU School of Medicine Graduate Student Research Fellowship

  $2

  Wayne State University School of Medicine

  NCI (T32) Fellowship

  declined due to overlap with DOD Traineeship

  National Cancer Institute

  WSU School of Medicine Research Award for Best Oral Presentation

  $800

  Wayne State University School of Medicine

• 000

  WSU Graduate Student External Support Award

  $2

  Wayne State University School of Medicine

  NSF FIRST IV Fellowship

  1/2011-6/2012\t

  National Science Foundation

  AACR-Aflac

  Scholar-in-Training Award for Associate Members

  $1000

  American Association for Cancer Research

  NIH Graduate Student Research Festival Poster Presentation

  Bethesda

  MD

  National Institute of Health

• Karmanos Cancer Institute

  Sexual Health Counselor

  Assist and shadow the doctor with pap smear testing and education and counseling on sexually transmitted infections and methods of contraception for college students and uninsured patients at Michigan State University.

  Gateway Community Health Clinic East Lansing

  MI

  First Response Counselor

  Education and counseling for victims of rape and violence.

  Turning Point

  Medical education and communications

  Molecular Biology

  Medicine

  Clinical Research

  Biotechnology

  Higher Education

  Pre-Clinical/Translational Research

  Immunology

  U.S. Health Insurance Portability and Accountability Act (HIPAA)

  Western Blotting

  Oncology

  Grant Writing

  Project Management

  Biochemistry

  Good Clinical Practice (GCP)

  Cell Culture

  Life Sciences

  Cell Biology

  Strategic Planning

  Pharmaceutical Industry

  Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts.

  Abstract\nPrevious studies have suggested that breast cancer stem cells (BCSCs) mediate metastasis

  are resistant to radiation and chemotherapy

  and contribute to relapse. Although several BCSC markers have been described

  it is unclear whether these markers identify the same or independent BCSCs. Here

  we show that BCSCs exist in distinct mesenchymal-like (epithelial-mesenchymal transition [EMT]) and epithelial-like (mesenchymal-epithelial transition [MET]) states. Mesenchymal-like BCSCs characterized as CD24(-)CD44(+) are primarily quiescent and localized at the tumor invasive front

  whereas epithelial-like BCSCs express aldehyde dehydrogenase (ALDH)

  are proliferative

  and are located more centrally. The gene-expression profiles of mesenchymal-like and epithelial-like BCSCs are remarkably similar across different molecular subtypes of breast cancer

  and resemble those of distinct basal and luminal stem cells found in the normal breast. We propose that the plasticity of BCSCs that allows them to transition between EMT- and MET-like states endows these cells with the capacity for tissue invasion

  dissemination

  and growth at metastatic sites.

  Breast cancer stem cells transition between epithelial and mesenchymal states reflective of their normal counterparts.

  Abstract\nMatrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) regulate epithelial-mesenchymal transition (EMT) critical for the development of epithelial organs as well as cancer cell invasion. TIMP-1 is frequently overexpressed in several types of human cancers and serves as a prognostic marker. The present study investigates the roles of TIMP-1 on the EMT process and formation of the lumen-like structure in a 3D Matrigel culture of MDCK cells. We show that TIMP-1 overexpression effectively prevents cell polarization and acinar-like structure formation. TIMP-1 induces expression of the developmental EMT transcription factors such as SLUG

  TWIST

  ZEB1 and ZEB2

  leading to downregulation of epithelial marker and upregulation of mesenchymal markers. Importantly

  TIMP-1's ability to induce the EMT-like process is independent of its MMP-inhibitory domain. To our surprise

  TIMP-1 induces migratory and invasive properties in MDCK cells. Here

  we present a novel finding that TIMP-1 signaling upregulates MT1-MMP and MMP-2 expression

  and potentiates MT1-MMP activation of pro-MMP-2

  contributing to tumor cell invasion. In spite of the fact that TIMP-1

  as opposed to TIMP-2

  does not interact with and inhibit MT1-MMP

  TIMP-1 may act as a key regulator of MT1-MMP/MMP-2 axis. Collectively

  our findings suggest a model in which TIMP-1 functions as a signaling molecule and also as an endogenous inhibitor of MMPs. This concept represents a paradigm shift in the current view of TIMP-1/MT1-MMP interactions and functions during cancer development/progression.

  TIMP-1 induces an EMT-like phenotypic conversion in MDCK cells independent of its MMP-inhibitory domain.

  Abstract\nCertain farnesyl diphosphate (FPP) analogs are potent inhibitors of the potential anticancer drug target protein farnesyltransferase (FTase)

  but these compounds are not suitable as drug candidates. Thus

  phosphoramidate prodrug derivatives of the monophosphate precursors of FPP-based FTase inhibitors have been synthesized. The monophosphates themselves were significantly more potent inhibitors of FTase than the corresponding FPP analogs. The effects of the prodrug 5b (a derivative of 3-allylfarnesyl monophosphate) have been evaluated on prenylation of RhoB and on the cell cycle in a human malignant schwannoma cell line (STS-26T). In combination treatments

  1-3 microM 5b plus 1 microM lovastatin induced a significant inhibition of RhoB prenylation

  and a combination of these drugs at 1 microM each also resulted in significant cell cycle arrest in G1. Indeed

  combinations as low as 50 nM lovastatin + 1 microM 5c or 250 nM lovastatin + 50 nM 5c were highly cytostatic in STS-26T cell culture.

  Synthesis

  biochemical

  and cellular evaluation of farnesyl monophosphate prodrugs as farnesyltransferase inhibitors.

  Abstract\nSomatic mutations or deletions of TP53 and PTEN in ductal carcinoma in situ lesions have been implicated in progression to invasive ductal carcinomas. A recent molecular and mutational analysis of breast cancers revealed that inactivation of tumor suppressors

  p53 and PTEN

  are strongly associated with triple negative breast cancer. In addition

  these tumor suppressors have important roles in regulating self-renewal in normal and malignant stem cells. To investigate their role in breast carcinogenesis

  we knocked down these genes in human mammary cells and in non-transformed MCF10A cells. p53 and PTEN knockdown synergized to activate pro-inflammatory interleukin-6 (IL6)/Stat3/nuclear factor κB signaling. This resulted in generation of highly metastatic epithelial-to-mesenchymal transition-like cancer stem cells resulting in tumors whose gene expression profile mimicked that found in basal/claudin-low molecular subtype within the triple negative breast tumors. Constitutive activation of this loop in transformed cells was dependent on proteolytic degradation of suppressor of cytokine signaling 3 (SOCS3) resulting in low levels of this protein in basal/claudin-low cell lines and primary tumors. In non-transformed cells

  transient activation of the IL6 inflammatory loop induced SOCS3 expression leading to pathway inactivation. In transformed cells

  enforced expression of SOCS3 or interfering with IL6 pathway via IL6R blockade inhibited tumor growth and metastasis in mouse xenograft models. Furthermore

  circulating tumor cells were significantly reduced in tumor-bearing animals when treated with anti-IL6R antibodies. These studies uncover important connections between inflammation and carcinogenesis and suggest that blocking pro-inflammatory cytokines may be utilized as an attractive strategy to target triple negative breast tumors

  which currently lacks molecularly targeted therapies.

  SOCS3-mediated regulation of inflammatory cytokines in PTEN and p53 inactivated triple negative breast cancer model.

  Development of Community-Engaged Research Training Course: Connecting Students

  Faculty

  and Community

  Abstract\nTissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of matrix metalloproteinases (MMPs) and the balance between MMPs/TIMPs regulates the extracellular matrix (ECM) turnover and remodeling during normal development and pathogenesis. Increasing evidence indicates a much more complex role for TIMPs during tumor progression and angiogenesis

  in addition to their regulation of MMP-mediated ECM degradation. In this article

  we review both the MMP-dependent and -independent actions of TIMPs for the regulation of cell death

  cell proliferation

  and angiogenesis

  with a particular emphasis on TIMP-1 in the regulation of tetraspanin/integrin-mediated cell survival signal transduction pathways.\n\nPMID: 16680576 DOI: 10.1007/s10555-006-7893-x

  Novel functions of TIMPs in cell signaling.

  Abstract\nAlthough inactivation of the PTEN gene has been implicated in the development of resistance to the HER2 targeting antibody trastuzumab

  the mechanisms mediating this resistance remain elusive. We generated trastuzumab resistant cells by knocking down PTEN expression in HER2 overexpressing breast cancer cell lines and demonstrate that development of trastuzumab resistance in these cells is mediated by activation of an IL6 inflammatory feedback loop leading to expansion of the cancer stem cell (CSC) population. Long term trastuzumab treatment generates highly enriched CSCs which display an EMT phenotype secreting over 100-fold more IL6 than parental cells. An IL6 receptor antibody interrupted this inflammatory feedback loop reducing the cancer stem cell population resulting in decreased tumor growth and metastasis in mouse xenographs. These studies demonstrate that trastuzumab resistance may be mediated by an IL6 inflammatory loop and suggest that blocking this loop may provide alternative strategy to overcome trastuzumab resistance.\n\n

  Activation of an IL6 inflammatory loop mediates trastuzumab resistance in HER2+ breast cancer by expanding the cancer stem cell population.

  Poster presentation and demonstration of concept mapping for Nutrient Metabolism

  Mapping Out Cellular Respiration

  TIMP-1 induces an epithelial mesenchymal transition via upregulation of the transcription factor Twist in human breast epithelial cells.

  Poster Presentation

  Gordon Research Conference on Basement Membranes

  Barga

  Italy

  June 18-23

  2006\n\n

  TIMP-1 regulation of tetraspanin/integrin survival signaling pathways affecting apoptosis

  cell-cell adhesion

  morphology and polarity of breast epithelial cells.

  Stem cells in normal development and cancer.

  Abstract\nIn this chapter we provide an overview of stem cells in normal tissues as well as in many different types of cancers. All tissues in the body are derived from organ-specific stem cells that retain the ability to self-renew and differentiate into specific cell types. The cancer stem cell hypothesis suggests that tumors arise from cell populations with dysregulated self-renewal. This may be tissue stem cells or more differentiated cells that acquire self-renewal capabilities. In addition

  we outline some useful assays for purification and isolation of cancer stem cells including the dye exclusion side population assay

  flow cytometry sorting techniques for identification of putative cancer stem cell markers

  tumorspheres assay

  aldehyde dehydrogenase activity assay

  PKH

  and other membrane staining used to label the cancer stem cells

  as well as in vivo xenograft transplantation assays. We also examine some of the cell signaling pathways that regulate stem cell self-renewal including the Notch

  Hedgehog

  HER2/PI3K/Akt/PTEN

  and p53 pathways. We also review information demonstrating the involvement of the microenvironment or stem cell niche and its effects on the growth and maintenance of cancer stem cells. Finally

  we highlight the therapeutic implications of targeting stem cells by inhibiting these pathways for the treatment and prevention of cancer.

  Stem cells in normal development and cancer.

  Abstract\nTissue inhibitor of metalloproteinase-1 (TIMP-1) regulates intracellular signaling networks for inhibition of apoptosis. Tetraspanin (CD63)

  a cell surface binding partner for TIMP-1

  was previously shown to regulate integrin-mediated survival pathways in the human breast epithelial cell line MCF10A. In the current study

  we show that TIMP-1 expression induces phenotypic changes in cell morphology

  cell adhesion

  cytoskeletal remodeling

  and motility

  indicative of an epithelial-mesenchymal transition (EMT). This is evidenced by loss of the epithelial cell adhesion molecule E-cadherin with an increase in the mesenchymal markers vimentin

  N-cadherin

  and fibronectin. Signaling through TIMP-1

  but not TIMP-2

  induces the expression of TWIST1

  an important EMT transcription factor known to suppress E-cadherin transcription

  in a CD63-dependent manner. RNAi-mediated knockdown of TWIST1 rescued E-cadherin expression in TIMP-1-overexpressing cells

  demonstrating a functional significance of TWIST1 in TIMP-1-mediated EMT. Furthermore

  analysis of TIMP-1 structural mutants reveals that TIMP-1 interactions with CD63 that activate cell survival signaling and EMT do not require the matrix metalloproteinase (MMP)-inhibitory domain of TIMP-1. Taken together

  these data demonstrate that TIMP-1 binding to CD63 activates intracellular signal transduction pathways

  resulting in EMT-like changes in breast epithelial cells

  independent of its MMP-inhibitory function.\n\nIMPLICATIONS:\nTIMP-1's function as an endogenous inhibitor of MMP or as a \"cytokine-like\" signaling molecule may be a critical determinant for tumor cell behavior.

  TIMP-1 via TWIST1 Induces EMT Phenotypes in Human Breast Epithelial Cells

  Developmental pathways such as notch play a pivotal role in tissue-specific stem cell self-renewal as well as in tumor development. however

  the role of notch signaling in breast cancer stem cells (csc) remains to be determined. we utilized a lentiviral notch reporter system to identify a subset of cells with a higher notch activity (notch(+)) or reduced activity (notch(-)) in multiple breast cancer cell lines. using in vitro and mouse xenotransplantation assays

  we investigated the role of the notch pathway in breast csc regulation. breast cancer cells with increased notch activity displayed increased sphere formation as well as expression of breast csc markers. interestingly notch(+) cells displayed higher notch4 expression in both basal and luminal breast cancer cell lines. moreover

  notch(+) cells demonstrated tumor initiation capacity at serial dilutions in mouse xenografts

  whereas notch(-) cells failed to generate tumors. γ-secretase inhibitor (gsi)

  a notch blocker but not a chemotherapeutic agent

  effectively targets these notch(+) cells in vitro and in mouse xenografts. furthermore

  elevated notch4 and hey1 expression in primary patient samples correlated with poor patient survival. our study revealed a molecular mechanism for the role of notch-mediated regulation of breast cscs and provided a compelling rationale for csc-targeted therapeutics. mol cancer ther; 14(3); 779-87. ©2015 aacr.

  Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity.