Carol Lange, PhD
Cancer and Cardiovascular Research Building
2231 6th Street SE
1st Floor Mailroom CCRB 2812A (Campus Delivery Code)
Minneapolis, MN 55455
United States
Dr. Lange is a Professor in the Departments of Medicine and Pharmacology at the University of Minnesota. She holds the Tickle Family Land Grant Endowed Chair of Breast Cancer Research. She received her PhD from the University of Colorado School of Pharmacy in 1991. She holds memberships in the American Association for Cancer Research (AACR), The Endocrine Society (ES) and Women in Endocrinology (WE). Dr. Lange serves as teaching faculty in the U of MN Department of Pharmacology Graduate Program, the Microbiology, Immunology, and Cancer Biology (MICAB) Graduate Program, the Genetics, Cell Biology, and Development (GCD) Graduate Program, and the MSTP (MD/PhD Combined) Program. She has served on several NIH Study Sections including Biochemical Endocrinology, Metabolic Physiology, Tumor Cell Biology, and Molecular Oncogenesis. She is on the Board of Scientific Advisors to the NIEHS. Dr. Lange is the Editor-in-Chief of the journal Hormones and Cancer (Springer/Nature publishers).
Professional Associations
- Member, American Association for Cancer Research (AACR); The Endocrine Society (ES)
- Director, Molecular, Genetics, and Cellular Targets of Cancer Training Program (T32), Masonic Cancer Center, University of Minnesota (2010-present)
- Co-Leader, Cellular Mechanisms Program, Masonic Cancer Center, University of Minnesota
- Tickle Family Land Grant Endowed Chair of Breast Cancer Research (2009-present)
- Editor in Chief, Hormones and Cancer
- Associate Editor, Breast Cancer Research; British Journal of Cancer
- Board of Scientific Advisors, NIEHS
- Scientific Advisory Board, Context Therapeutics, Inc.
Education
Professor of Medicine, Division of Hematology, Oncology and Transplantation
Tickle Family Land Grant Endowed Chair of Breast Cancer Research
Program co-Leader, Cellular Mechanisms,, Masonic Cancer Center (MCC)
Faculty, Microbiology, Immunology and Cancer Biology (MICaB) Ph.D. Graduate Program
Faculty, MS and PhD Programs in Pharmacology
Faculty, Molecular and Cellular Therapeutics
Preceptor, Medical Scientist Training Program (Combined MD/PhD Training Program)
PhD, University of Colorado School of Pharmacy, Boulder, CO
Research
Research Summary/Interests
The Lange Lab is focused on the role of steroid hormone receptors (SRs) in breast and ovarian cancers. Estrogen receptor (ER) and progesterone receptors (PRs) are ligand-activated and context-dependent transcription factors that are essential for development of the breast and reproductive tract. Altered sex hormone levels contribute to cancer risk in these tissues and drive metabolic and cell fate transitions associated with rapid tumor progression. The presence of abnormally activated ERs and imbalanced/activated PR and GR isoforms in hormone-driven tumors can dramatically influence response to endocrine or other therapies. Our overarching research goal is to better understand how SR+ breast cancers and other hormone-influenced cancers of reproductive tissues escape endocrine (i.e. SR-blocking) or other molecular targeted therapies that primarily target signaling pathways that are active in proliferating cancer cells.
Ongoing projects encompass the following research themes and their molecular mechanisms:
• ER and PR isoform signaling cross talk in luminal breast cancer progression
• Ligand-independent actions of p-SRs and p-SR-containing complexes in breast cancer
• Altered SR actions in the context of ESR1 mutations or BRCA1/2 loss or mutation
• Cellular “stress” sensing by phospho-GR in triple negative breast cancer progression
• Fallopian tube transformation and early SR+ serous ovarian cancer progression
• Cell fate plasticity (cell cycle exit/entry into G0) and breast cancer stem cell biology
• Mechanisms of and biological role of cancer cell dormancy/quiescence and senescence
• SR and signaling pathway regulation of breast cancer stem cell populations and biology
• Breast cancer metastatic cell dissemination as circulating tumor cell/stem cell clusters
Publications
Insulin Receptor Substrate-1 (IRS-1) Mediates Progesterone Receptor-Driven Stemness and Endocrine Resistance in Estrogen Receptor+ Breast Cancer. Dwyer AR, Truong TH, Perez Kerkvliet C, Paul KV, Kabos P, Sartorius CA, Lange CA. British Journal of Cancer, in press (July 2020).
Glucocorticoid receptors are required effectors of TGF?1-induced p38 MAPK signaling to advanced cancer phenotypes in triple-negative breast cancer. Perez Kerkvliet C, Dwyer AR, Diep CH, Oakley RH, Liddle C, Cidlowski JA, Lange CA. Breast Cancer Res. 2020 May 1;22(1):39.
Phosphorylated Progesterone Receptor Isoforms Mediate Opposing Stem Cell and Proliferative Breast Cancer Cell Fates. Truong TH, Dwyer AR, Diep CH, Hu H, Hagen KM, Lange CA. Endocrinology. 2019 Feb 1;160(2):430-446.
Taxol Induces Brk-dependent Prosurvival Phenotypes in TNBC Cells through an AhR/GR/HIF-driven Signaling Axis. Regan Anderson TM, Ma S, Perez Kerkvliet C, Peng Y, Helle TM, Krutilina RI, Raj GV, Cidlowski JA, Ostrander JH, Schwertfeger KL, Seagroves TN, Lange CA. Mol Cancer Res. 2018 Nov;16(11):1761-1772.
Cancer Stem Cell Phenotypes in ER+ Breast Cancer Models Are Promoted by PELP1/AIB1 Complexes. Truong TH, Hu H, Temiz NA, Hagen KM, Girard BJ, Brady NJ, Schwertfeger KL, Lange CA, Ostrander JH. Mol Cancer Res. 2018 Apr;16(4):707-719.
Posttranslationally modified progesterone receptors direct ligand-specific expression of breast cancer stem cell-associated gene programs. Knutson TP, Truong TH, Ma S, Brady NJ, Sullivan ME, Raj G, Schwertfeger KL, Lange CA. J Hematol Oncol. 2017 Apr 17;10(1):89.
Breast Tumor Kinase (Brk/PTK6) Is Induced by HIF, Glucocorticoid Receptor, and PELP1-Mediated Stress Signaling in Triple-Negative Breast Cancer. Regan Anderson TM, Ma SH, Raj GV, Cidlowski JA, Helle TM, Knutson TP, Krutilina RI, Seagroves TN, Lange CA. Cancer Res. 2016 Mar 15;76(6):1653-63.
Active FOXO1 Is a Key Determinant of Isoform-Specific Progesterone Receptor Transactivation and Senescence Programming. Diep CH, Knutson TP, Lange CA. Mol Cancer Res. 2016 Feb;14(2):141-62.