Karen Liby, Ph.D.
Pharmacology & Toxicology
B430 Life Sciences
1355 Bogue Street
East Lansing, MI 48823
Fields of Interest: Inflammation, cancer and drug development
- 1994 - B.S., Biology, Hillsdale College
- 1997 - M.S., Anatomy, Palmer College
- 2002 - Ph.D., Cell and Molecular Biology, University of Cincinnati College of Medicine
- 2003-2007 - Postdoctoral Fellow, Dartmouth Medical School
- 2007-2012 - Research Assistant Professor, Dartmouth Medical School
- 2012-2015 - Research Associate Professor, Dartmouth Medical School
- 2015-present - Associate Professor, Pharmacology & Toxicology, Michigan State University
Biography & Current Research
The overall goals of my research are to study the role of inflammation in cancer and to develop and test new drugs for the prevention or treatment of cancer and other chronic diseases. Lung cancer, pancreatic cancer, and a subset of breast cancer (estrogen receptor negative or ER-) are three of the leading causes of cancer death, and we use the most relevant mouse models available of these diseases to study the development of these cancers and to test new drugs.
xcessive inflammation contributes to the pathogenesis of many human diseases. During the inflammatory process, immune cells produce the chemical mediator nitric oxide (NO), and NO and other inflammatory cytokines can cause severe tissue damage. We have developed a number of assays to screen for drugs that inhibit inflammation and will use the Drug Repurposing Core Facility to screen available libraries. We are also interested in establishing screens and developing new triterpenoids, bromodomain inhibitors, and rexinoids.
There is a major need to develop new agents for the prevention and treatment of pancreatic cancer as this disease is usually fatal, with an average survival of only 4-6 months and a 5-year survival rate of less than 5%. The disease is not usually symptomatic until late stages and is often resistant to all forms of conventional chemotherapy. Mouse models of pancreatic cancer (KPC or KC mice) have been developed that closely resemble human pancreatic cancer. Chronic pancreatitis, or inflammation of the pancreas, is a well-known risk factor for developing pancreatic cancer, and we have developed a new protocol for studying the effects of inflammation in KC mice. We are studying the effects of a variety of anti-inflammatory drugs on a) cytokine production and immune cell infiltration/activation in the pancreas and b) pancreatic cancer progression.
Lung cancer is the leading cause of cancer deaths in the U.S. and throughout the world, highlighting the need to develop better drugs to prevent or treat this disease. We recently discovered that the synthetic triterpenoids and dimethyl fumarate activate the cytoprotective Nrf2 pathway but have opposite effects in a model of experimental lung cancer. We are interested in studying the effects of Nrf2 activation for both prevention and treatment of this disease.
Breast cancer is the most frequently diagnosed cancer in women and claims more than 40,000 lives each year. Despite significant advances in the treatment of breast cancer, the prognosis for breast cancers which do not express the estrogen receptor (ER- breast cancer) has not changed significantly in more than 30 years. In human breast cancer, the BRCA1 gene is frequently mutated in women with a family history of breast cancer, and carriers of BRCA1 mutations have a 65-85% lifetime risk of developing breast cancer. Currently, “watchful waiting” or prophylactic removal of the breasts is offered to these patients, although these high risk women are ideal candidates for an effective, safe chemoprevention regimen. We have shown that the PARP inhibitor olaparib can significantly delay tumor development in a mouse model of BRCA1-deficiency. Moreover, intermittent treatment with olaparib was just as effective as continuous treatment and was able to kill early lesions in the mammary glands of this model. Although olaparib has recently been approved for treatment of ovarian cancer in women with BRCA mutations, more potent PARP inhibitors are currently in clinical trials. We are collaborating with investigators interested in testing new PARP inhibitors and new formulations of PARP inhibitors (nanoparticles) in our animal model.
Inflammation can contribute to the development of breast cancer. Immune cells known as tumor associated macrophages (TAMs) are a primary cause of inflammation in breast cancer, as these cells produce cytokines that drive angiogenesis and tumor progression. We have recently shown that triterpenoids and other anti-inflammatory drugs can delay tumor development in the PyMT model of ER- breast cancer by targeting macrophages. We are testing drugsfor their ability to reprogram TAMs from an M2 immuno-suppressive phenotype to and M1 immuno-stimulating phenotype both in vitro and in vivo.
Awards & Achievements
- 1999-2002, DOD Breast Cancer Research Predoctoral Fellowship
- 2001-2002, Albert J. Ryan Fellowship
- 2003-2006, Robert E. Gosselin Postdoctoral Fellowship
- 2007, Wilson E. Stone Memorial Award
- 2008-2010, Sidney Kimmel Research Scholar Award
Committees & Activities
- 2010-2013, 2015 - ad hoc reviewer for the NIH Chemo/Dietary Prevention Study Section
- 2011 - Member of the Scientific Program Committee for AACR Frontiers in Cancer Prevention Research meeting
- 2012 - ad hoc reviewer for the NIH Cancer Prevention Research R03 study section
- 2015-present - Member of the Editorial Board of Cancer Prevention Research
- Liby K, Yore MM and Sporn MB. Triterpenoids and rexinoids as multifunctional agents for prevention and treatment of cancer. Nat Rev Cancer 7:357-69, 2007
- Liby KT and Sporn MB. Synthetic oleanane triterpenoids: multifunctional drugs with a broad range of applications for prevention and treatment of chronic disease. Pharm Rev 64:972-1003, 2012.
- Tran K, Risingsong R, Royce D, Williams CR, Sporn MB, Pioli PA, Gediya LK, Njar VC and Liby KT. The combination of the histone deacetylase inhibitor vorinostat and synthetic triterpenoids reduces tumorigenesis in mouse models of cancer. Carcinogenesis 34:199-210, 2013.
- To C, Kim EH, Royce DB, Williams CR, Collins RM, Risingsong R, Sporn MB and Liby KT. The PARP inhibitors, veliparib and olaparib, are effective chemopreventive agents for delaying tumor development in BRCA1-deficient mice. Can Prev Res 7:698-707, 2014.
- To C, Ringelberg C, Royce DB, Williams CR, Risingsong R, Sporn MB and Liby KT. Dimethyl fumarate and the oleanane triterpenoids, CDDO-Imidazolide and CDDO-Methyl Ester, both activate the Nrf2 pathway but have opposite effects in the A/J model of lung carcinogenesis. Carcinogenesis 36:769-81, 2015.
Additional Publications available at PubMed