|Huiping Liu, M.D., Ph.D.
Department of Pathology
Case Comprehensive Cancer Center
Case Western Reserve University
2103 Cornell Rd.
Cleveland, OH 44106-7288
Dr. Huiping Liu received a medical degree and M.S. in Biochemistry & Molecular Biology from China. She obtained a Ph.D. in Biomedical Sciences (Molecular Pathogenesis & Molecular Medicine) at the University of Chicago in 2006. Her PhD thesis research with Dr. Kay Macleod focused on the role of the RB tumor suppressor in chemotherapy resistance. In 2007, Dr. Liu started her postdoctoral training with Dr. Michael Clarke at Stanford University and later received a DOD Breast Cancer Research Program Postdoctoral Fellowship (transferred to the University of Chicago in 2009). Her work demonstrated that breast cancer stem cells play an important role in spontaneous metastases in human-in-mouse breast cancer models (PNAS, 2010). In collaboration with Drs. Sanjiv Sam Gambhir, Christopher Contag, and John Condeelis, Dr. Liu also developed an improved optical imaging approach to monitor the activities of primary human tumor cells in mice.
As one of only three first-generation University of Chicago Fellows in 2009, Dr. Liu continued her advanced training with Dr. Geoffrey Greene at the University of Chicago with Dr. Michael Clarke as her co-mentor. This prestigious award was designed to promote the Postdoctoral Scholar-to-Faculty transition. Dr. Liu subsequently received two career development awards, the NCI-funded Paul Calabresi K12 Scholar of Clinical Oncology Award in 2011 and the NCI-funded K99 award, the Pathway to Independence Award, in 2012. Dr. Liu has recently focused on dissecting the role of microRNAs in breast cancer stem cells, metastasis, and therapy resistance.
Dr. Liu joined the Department of Pathology at Case Western Reserve University on November 1, 2013. She has a secondary appointment in the Case Comprehensive Cancer Center. Dr. Liu has been actively bridging basic science, engineering, and clinical medicine, through collaborating with physicians and researchers across many institutions, including oncologists Drs. Lyndsay Harris (CWRU), Hannah Gilmore (CWRU), Funmi Olopade (UChicago), and Patrick Ma (CCF), bioengineers Dr. Matthew Tirrell (UChicago) and Seungpyo Hong (UIC), geneticist Dr. Anthony Wynshaw-Boris (CWRU), bioinformaticist Charles Perou (UNC), and biostatisticians Drs. Robert Elson (CWRU) and Omar De la Cruz C. (CWRU).
Metastasis causes 90% of the mortality associated with solid tumors, such as breast cancer. Cancer metastasis is a multi-step process of cancer cell migration from the primary tumor sites to the distant secondary tumor sites. However, the molecular mechanisms underlying metastasis remain poorly understood and no effective approaches are available to cure metastasis. The goals of the Liu laboratory are to control metastasis and eliminate the mortality associated with breast cancer and other types of cancer.
The identification of cancer stem cells (CSCs), a subpopulation of cancer cells with stem cell properties, has brought us a new perspective on cancer, including leukemia and solid tumors. CSCs are proposed to mediate cancer relapse and metastasis due to their resistance to conventional therapies. Dr. Liu’s previous work has demonstrated that breast cancer stem cells (BCSCs) are able to mediate spontaneous lung metastases in human-in-mouse xenograft models. Her work has identified that miR-30c is a direct target of GATA3 in regulating both invasion and chemo-resistance, through targeting TWF1 and VIM (Nat Commu 2013, BRCT 2013) (Figure 1). Nevertheless, complete understanding, efficient imaging, effective targeting, and strategic differentiation of CSCs are among the most challenging tasks in cancer treatment.
We have four ongoing interactive basic and translational research directions (Figure 2): (1) to understand cancer stem cells (CSCs) using cutting-edge single cell sequencing technology and functional studies; (2) to image CSCs (their dynamic behavior and interactions with immune cells and non-CSCs) during metastasis using bioluminescence imaging and intravital imaging systems; (3) to target CSCs with novel therapeutics delivered by nanoparticles; (4) to re-differentiate CSCs.
Publications (8 of 29)
- MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11. Nature Communications. Bockhorn J, Dalton R, Nwachukwu C, Huang S, Prat A, Yee K, Chang YF, Huo D, Wen Y, Swanson KE, Qiu T, Lu J, Park SY, Dolan ME, Perou CM, Olopade OI, Clarke MF, Greene GL, Liu H. Nature Communications. 2013;4:1393. doi: 10.1038/ncomms2393. PMID: 23340433 Free PMC Article
- MicroRNA-30c targets cytoskeleton genes involved in breast cancer cell invasion. Bockhorn J, Yee K, Chang YF, Prat A, Huo D, Nwachukwu C, Dalton R, Huang S, Swanson KE, Perou CM, Olopade OI, Clarke MF, Greene GL, Liu H. Breast Cancer Res Treat. 2013 Jan;137(2):373-82. doi: 10.1007/s10549-012-2346-4. Epub 2012 Dec 7. PMID: 23224145
- MicroRNAs in breast cancer initiation and progression. Liu H. Cell Mol Life Sci. 2012 Nov;69(21):3587-99.
- Removal of lactate dehydrogenase-elevating virus from human-in-mouse breast tumor xenografts by cell-sorting. Liu H, Bockhorn J, Dalton R, Chang YF, Qian D, Zitzow LA, Clarke MF, Greene GL.J Virol Methods. 2011 May;173(2):266-70. doi: 10.1016/j.jviromet.2011.02.015. Epub 2011 Feb 24. PMID: 21354210 Free PMC Article
- Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models. Liu H, Patel MR, Prescher JA, Patsialou A, Qian D, Lin J, Wen S, Chang YF, Bachmann MH, Shimono Y, Dalerba P, Adorno M, Lobo N, Bueno J, Dirbas FM, Goswami S, Somlo G, Condeelis J, Contag CH, Gambhir SS, Clarke MF. Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18115-20. doi: 10.1073/pnas.1006732107. Epub 2010 Oct 4. PMID: 20921380 Free PMC Article
- Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E, Dirbas FM, Somlo G, Pera RA, Lao K, Clarke MF. Cell. 2009 Aug 7;138(3):592-603.
- Elevated poly-(ADP-ribose)-polymerase activity sensitizes retinoblastoma-deficient cells to DNA damage-induced necrosis. Liu H, Knabb JR, Spike BT, Macleod KF.Mol Cancer Res. 2009 Jul;7(7):1099-109. doi: 10.1158/1541-7786.MCR-08-0439. Epub 2009 Jul 7. PMID: 19584263 Free PMC Article
- New roles for the RB tumor suppressor protein. Liu H, Dibling B, Spike B, Dirlam A, Macleod K. Curr Opin Genet Dev. 2004 Feb;14(1):55-64. PMID: 15108806