• Welcome to the Carpenter Lab

  • Research

    Metastasis, or the spread of tumors to other organs, plays a highly significant role in cancer biology considering that more than 90% of cancer deaths are attributable to metastasis. Metastasis is a complex, step-wise process whereby cells at a primary tumor site, such as the breast, gain the ability to leave the primary tumor and travel in the circulation to colonize in a new host organ, such as the brain.

    In order for cells to gain the ability to leave the primary tumor, the cell is reprogrammed by the resulting signaling pathways and activated transcription factors. Therefore, transcription factors sit at the nexus of cellular signaling pathways and genomic programs that alter the phenotype of the cell. We study the molecular mechanisms in cancer cells that regulate transcription factors and the subsequent genomic programs written by these transcription factors that lead to an altered phenotype. In particular, we are interested in the transcriptional programs that promote tumor progression and metastasis. In our lab, we utilize a wide breadth of techniques ranging from cell signaling analysis using proteins, to protein-DNA interactions, to RNA expression, and bioinformatics approaches to assess genomic programs by transcription factors. We also utilize multiple in vitro and in vivo models to assess cell migration and invasion, tumor angiogenesis, tumor growth, and metastasis.

    Heat Shock Factor 1 (HSF1) in Breast Cancer


    We recently discovered that the transcription factor HSF1, widely known as the master regulator of the heat shock response, plays a key role in the early steps of metastasis in HER2-positive breast cancer. Our findings indicated that the cellular kinase AKT can directly activate HSF1 leading to the expression of the gene for Slug, a transcriptional repressor known to promote epithelial-to-mesenchymal transition (EMT). EMT is a reprogramming of epithelial-like tumor cells to a phenotype more characteristic of mesenchymal cells such that they have a much higher capability for movement throughout the tissue and organism.

    EMT is widely considered to be an early step in the process of metastasis. Our findings indicate that AKT-driven activity of HSF1 can induce EMT via upregulation of Slug. Interestingly, AKT and HSF1 are also activated in other subtypes of breast cancer. This likely stems from the fact that the PI3K-AKT pathway is activated in over 75% of all breast cancers. Our current work is investigating the mechanisms by which HSF1 promotes metastasis via EMT and cancer stem cell phenotypes, whether this pathway can be targeted to suppress metastasis, and identifying the gene signatures that occur when HSF1 is activated.

    Truncated GLI1 (tGLI1)

    GLI1 is the transcription factor that is the terminal effector of the Sonic Hedgehog (Shh) signaling pathway. GLI1 was originally identified as an amplified gene in glioblastoma (GBM) and has a complex role in embryonic development but also has become associated with tumor development and tumor progression. An alternative splice variant of GLI1 was identified in 2009 that is missing 41 amino acids compared to the wild-type GLI1 protein and was thus named truncated GLI1 (or tGLI1). Interestingly, tGLI1 was exclusively expressed in tumor tissues and has not been observed in any healthy tissues to date. Furthermore, tGLI1 expression was found to drive migration and invasion of GBM and breast cancer cells. We have further characterized tGLI1 to have a potent pro-angiogenic effect by direct upregulation of angiogenic genes and tGLI1 has a role in promoting the cancer cell phenotype. Our current work is investigating the mechanisms driving tGLI1 exclusive expression in tumor cells, the mechanisms by which tGLI1 promotes an invasive phenotype, and the gene programs induced by tGLI1 expression.

  • Publications

    1. Carpenter RL, Gokmen-Polar Y. HSF1 as a Cancer Biomarker and Therapeutic Target. Current Cancer Drug Targets. IN PRESS, 2019.
    2. Carpenter RL, Ray H. Safety and Tolerability of Sonic Hedgehog Pathway Inhibitors in Cancer. Drug Safety. IN PRESS, 2019.
    3. Carpenter RL, Paw I, Dewhirst MW, Lo HW. AKT Phosphorylates and Activates HSF-1 Independent of Heat Shock, Leading to Slug Overexpression and Epithelial-Mesenchymal Transition (EMT) of HER2-Overexpressing Breast Cancer Cells. Oncogene. 34(5): 546-557, 2015.
    4. Carpenter RL, Sirkisoon S, Zhu D, Rimkus T, Harrison A, Anderson A, Paw I, Qasem S, Xing F, Liu Y, Chan M, Metheny-Barlow L, Pasche BC, Debinski W, Watabe K, Lo HW. Combined inhibition of AKT and HSF1 suppresses breast cancer stem cells and tumor growth. Oncotarget. 8(43):73947-73963, 2017.
    5. *Carpenter RL, *Zhu H, Han W, Lo HW. The GLI1 Splice Variant TGLI1 Promotes Glioblastoma Angiogenesis and Growth. Cancer Letters. 343(1):51-61, 2014. (*Denotes co-first author)
    6. Carpenter RL, Paw I, Zhu H, Sirkisson S, Xing F, Watabe K, Debinski W, Lo HW. The gain-of-function GLI1 transcription factor TGLI1 enhances expression of VEGF-C and TEM7 to promote glioblastoma angiogenesis. Oncotarget. 6(26):22653-65, 2015.
    7. *Carpenter RL, *Sirkisoon S, Rimkus T, Anderson A, Harrison A, Lange AM, Jin G, Watabe K, Lo HW. Interaction between STAT3 and GLI1/tGLI1 oncogenic transcription factors promotes the aggressiveness of triple-negative and HER2-enriched breast cancers. Oncogene. IN PRESS, 2017. (*Denotes co-first author)
    8. Carpenter RL, Lo HW. Identification, functional characterization, and pathobiological significance of GLI1 isoforms in human cancers. Vitamins and Hormones. Academic Press. Vol 88:115-140, 2012.
    9. Carpenter RL, Lo HW. Hedgehog pathway and GLI1 isoforms in human cancer. Discovery Medicine. 69:105-13, 2012.

    Dr. Carpenter's ORCID & NCBI Bibliography

  • Lab Members

    Assistant Professor

    Dept. of Biochemistry and Molecular Biology

    Medical Sciences Program

    Postdoctoral Fellow, Wake Forest University School of Medicine

    Postdoctoral Associate, Duke University School of Medicine

    Ph.D., Thomas Jefferson University

    B.S., West Virginia University

    Postdoctoral Fellow

    Ph.D., Indiana University School of Medicine

    B.S., Vanderbilt University

    Visiting Scholar

    Ph.D., Shanxi University of Chinese Medicine

    B.S., Xi'an Jiaotong University

    Cell, Molecular and Cancer Biology Ph.D. Student

    B.S., DePauw University

    Genome, Cell and Developmental Biology Ph.D. Student

    B.S., Harris-Stowe State University

    Cell, Molecular and Cancer Biology Ph.D. Student

    B.S., Rollins College

    Lab Manager

    B.S., Indiana University

    Laboratory Technician

    B.S., Indiana University

    Cox Research Scholar

    Class of 2021, Indiana University

    Undergraduate Researcher

    Class of 2021, Indiana University

    Undergraduate Researcher

    Class of 2022, Indiana University

    Undergraduate Researcher

    Class 2023, Indiana University

    High School Researcher

    Class of 2020, Bloomington North High School

  • Join Our Group

    We accept Ph.D. students from our Cell, Molecular and Cancer Biology (CMCB) program and the Genome, Cell, and Developmental Biology program and are actively recruiting students from these programs.

  • Carpenter Lab Alumni

    Wen-Cheng (Norman) Lu, Ph.D.

    Research Scientist, Rgenta Therapeutics

    Haley Temple, B.S.

    Research Assistant, Cincinnati Children's Hospital Medical Center

  • Contact Us

    Richard's email : : richcarp@iu.edu

    Carpenter Lab Twitter: @carpenter_lab

    Richard’s office phone: (812) 855-8214

    Richard’s lab phone: (812) 855-8709

    Jordan Hall Rm 313,

    Indiana University, Bloomington

  • Funding