Carol Lange, PhD

Professor of Medicine, Division of Hematology, Oncology and Transplantation

Carol Lange

Contact Info

lange047@umn.edu

Office Phone 612-626-0621

Lab Phone 612-624-1971

Mailing Address:
Cancer and Cardiovascular Research Building
2231 6th Street SE
1st Floor Mailroom CCRB
2812A (Campus Delivery Code)
Minneapolis, MN 55455

Administrative Assistant Name
Marilyn Lingard

Administrative Phone
612-625-1405

Administrative Email
linga012@umn.edu

Administrative Fax Number
612-626-3069

PhD, University of Colorado School of Pharmacy, Boulder, CO

Summary

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.

Research

Research Summary/Interests

My research team is focused on the role of steroid hormone receptors (SRs) in breast and ovarian cancers. Estrogen receptor ? (ER) and progesterone receptors (PRs) are 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 isoforms in SR+ 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 proliferating cells. Strategies aimed at targeting metabolically active, but weakly proliferative or non-proliferative (G0) cancer stem or heterogeneous stem-like cell sub-populations as well as highly migratory dormant or quiescent cells (i.e. living as disseminated “active” G0 cells in the circulation or within distant “cancerized” tissue niches) would provide a powerful complement to existing therapeutic strategies. Novel signaling pathway biomarkers may inform new combination therapies.

Signal transduction is an essential role of SRs. Indeed, all SRs can rapidly activate cytoplasmic protein kinases and act as “growth factor sensors”. In this role, SRs are heavily phosphorylated by mitogenic protein kinases (MAPKs, AKT, CDKs) that are frequently elevated and activated in breast and reproductive tract cancers. Phosphorylation of SRs alters their binding partners and promoter selection and influences cancer cell fate/plasticity by regulating genes that specify proliferative, pro-survival, metabolic, and cancer stem cell programs via expression of both autocrine and paracrine factors. Similarly (i.e. via rapid signaling and phosphorylation events), the glucocorticoid receptor (GR) acts as a sensor for both host (i.e. hormonal) and cellular stress, in the form of local cytokines and/or hypoxic conditions within the tumor microenvironment. Identifying the required kinase and co-activator partners of phospho-SRs will enable the targeting of multiple signaling molecules in addition to SRs, which is predicted to halt cancer metastasis, prevent recurrence, and increase patient survival.

My lab has extensive experience developing and using human cancer cell lines and primary cells, genetically modified mouse models, and human tumor specimens. We have routinely developed new reagents and employed classical biochemistry and molecular biology techniques to study SR action and novel mechanisms of gene regulation that impact breast tumor development and progression, cancer stem cell biology, and endocrine therapy resistance. More recently, we have included significant focus on the development of early SR+ fallopian tube lesions that give rise to high grade serous ovarian cancer. We typically complement in vitro studies focused on the mechanisms of signaling inputs to SR-dependent regulation of transcription with the use of genetically modified mice or human patient derived xenograft (PDX) models maintained in mice.

Ongoing projects encompass the following research themes and their molecular mechanisms:

  • ERa 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
  • Cellular “stress” sensing by phospho-GR in triple negative breast cancer progression
  • Novel HIF/GR-induced signaling pathways mediated by Breast Tumor Kinase/PTK6
  • 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
  • As a research advisor and Training Program Director, I am committed to providing high quality training and mentoring in a supportive environment that fosters creativity and embraces diversity. Outside the research lab, I encourage opportunities for my advisees to meet other scientist peers and future colleagues, and fully support their participation in professional development activities. Over the past 20 years as an independent investigator, I have mentored trainees at all levels, including as primary advisor to 12 predoctoral and 12 postdoctoral trainees, and have served as faculty mentor to numerous junior faculty members in my leadership roles within the Clinical and Translational Science Institute (CTSI) Internal Advisory Board and the University of Minnesota Masonic Cancer Center (MCC), where I serve as the co-Director of the Cellular Mechanisms Program. I have a long-standing interest in research career development, and have routinely organized professional (academic and non-academic) career and leadership development events designed for young people pursuing research careers both locally and nationally, and through my career-long affiliation with The Endocrine Society.