William P. Schiemann is the Goodman-Blum Professor in Cancer Research in the Case Comprehensive Cancer Center. Dr. Schiemann received his BS in Premedicine from the University of Nevada-Reno in 1990. After receiving his PhD in Pharmacology from the University of Washington in 1996, Dr. Schiemann joined the laboratory of Dr. Harvey F. Lodish at the Whitehead Institute for Biomedical Research and MIT, where he initiated studies of the “TGFβ- Paradox” and its role in driving breast cancer metastasis and disease recurrence. In 2001, Dr. Schiemann expanded these analyses as an independent investigator, initially as an Assistant Professor at National Jewish Health (Denver, CO) and subsequently as an Associate Professor at the University of Colorado School of Medicine (Aurora, CO). In 2010, Dr. Schiemann moved his research program to Case Western Reserve University and its Comprehensive Cancer Center, wherein he continues to elucidate the molecular mechanisms that underlie breast cancer development, metastasis, and disease recurrence.
- TGFβ & Cell Signaling
- Breast Cancer Metastasis & Recurrence
- Metastatic Dormancy
- Breast Cancer Stem Cells
- Epithelial-mesenchymal Transition
- Tumor Heterogeneity
- Noncoding RNAs
Metastatic breast cancer remains the second leading cause of cancer-related death in women in the US, annually accounting for more than 40,000 deaths and 250,000 new cases of invasive breast cancer. Metastatic breast cancer is incurable and results in a median survival of only 1.5 to 3 years. Moreover, ~30% of breast cancer patients diagnosed with early-stage disease will ultimately progress to metastatic disease, an event that (i) severely limits treatment options, (ii) typically results in chemoresistance and low response rates, and (iii) greatly contributes to aggressive relapses and dismal survival rates. This therapeutic barrier reflects the ability of disseminated tumor cells to acquire dormancy-associated phenotypes and escape clinical detection for many years by remaining in a state of “suspended animation,” only to recur as incurable secondary tumors. Thus, a major barrier to eradicating metastatic breast cancer reflects the paucity of knowledge related to how metastatic dormancy is initiated, maintained and overcome, and to how these metastatic “time bombs” can be defused in breast cancer patients. A major goal of the Schiemann Lab is to identify the cellular and molecular defects that enable breast cancers to establish and eventually emerge from metastatic dormancy. Accordingly, we seek to: (i) identify the initiating genetic and epigenetic defects that underlie the transformation of normal mammary stem cells, as well as determine the clinical utility of these events to mark and predict for metastatic progression in breast cancer patients; (ii) discover the molecular and cellular features that underlie the heterogeneity and diversity of human breast cancers, as well as determine the impact of these events on breast cancer metastasis, disease recurrence and chemoresistance; and (iii) identify the cellular and molecular deficiencies that give rise to the establishment and eventual emergence from metastatic dormancy.
Current Research Projects
- Role of the lncRNA BORG and Other Noncoding RNAs in Breast Cancer Metastasis and Recurrence
- Role of MYC-MIZ1 Signaling and the Inflammatory Immune Microenvironment in TNBC Racial Disparities
- Role of SLX4IP in Directing Breast Cancer Telomere Homeostasis, Metastatic Progression, and Recurrence
- Elucidating the Interplay Between Pfkfb3 and Autophagy in Regulating Breast Cancer Cell Acquisition of and Eventual Emergence From Metastatic Dormancy
- Determine the Epigenetic Events Coupled to Mammary Stem Cell Transformation and Metastatic Progression
- Gooding, AJ, Zhang, B, Gunawardane, L, Beard, A, Valadkhan, S and Schiemann, WP. (2018) The lncRNA BORG facilitates the survival and chemoresistance of triple-negative breast cancers. Oncogene. DOI: 10.1038/s41388-018-0586-4.
- Covarrubias, G, Cha, A, Rahmy, A, Lorkowski, M, Perera, V, Erokwu, BO, Flask, C, Peiris, PM, Schiemann, WP and Karathanasis, E. (2018) Imaging breast cancer using a dual-ligand nanochain particle. PLoS ONE. 13:e0204296. DOI: 10.1371/journal.pone.0204296.
- Peiris, PM, He, F, Covarrubias, G, Raghunathan, S, Turan, O, Lorkowski, M, Gnanasambandam, B, Wu, C, Schiemann, WP and Karathanasis, E. (2018) Precise targeting of cancer metastasis using multi-ligand nanoparticles incorporating four different ligands. Nanoscale. DOI: 10.1039/c8nr02513d.
- Sossey-Alaoui, K, Pluskota, E, Szpak, D, Schiemann, WP and Plow, EF. (2018) The Kindlin-2 regulation of epithelial-to-mesenchymal transition in breast cancer metastasis is mediated through miR-200b. Sci Rep. 8:7360. DOI: 10.1038/s41598-018-25373-0
- Gooding, AJ, Zhang, B, Jahanbani, FK, Gilmore, HL, Chang, JC, Valadkhan, S and Schiemann, WP. (2017) The lncRNA BORG drives breast cancer metastasis and disease recurrence. Sci Rep. 7:12698. DOI: 10.1038/s41598-017-12716-6* *Featured in “Mammary Cell News” volume 9.39, October 5, 2017. *“Top 100 in Oncology 2017,” Scientific Reports (12th out of >2000 published Oncology-related papers).
- Tian, M and Schiemann, WP. (2017) TGF-beta stimulation of EMT programs elicits non-genomic ER-alpha activity and anti-estrogen resistance in breast cancer cells. J Cancer Metastasis Treat. 3:150-161. DOI: 10.20517/2394-4722.2017.38
- Han, Z, Wu, X, Roelle, S, Chen, C, Schiemann, WP and Lu, ZR. (2017) Targeted gadofullerene for sensitive magnetic resonance molecular imaging and risk-stratification of breast cancer. Nat Commun. 8:692. DOI: 10.1038/s41467-017-00741-y.
- Sossey-Alaoui, K, Pluskota, E, Bialkowska, K, Szpak, D, Parker, Y, Morrison, CM, Lindner, D, Schiemann, WP and Plow, E. (2017) Kindlin-2 regulates the growth of breast cancer tumors by activating CSF-1-mediated macrophage infiltration. Cancer Res. 77:5129-5141.
- Morrison, CD, Chang, JC, Keri, RA and Schiemann, WP. (2017) Mutant p53 dictates the oncogenic activity of c-Abl in triple-negative breast cancers. Cell Death Dis. 8:e2899.* *Top Story in “Mammary Cell News” volume 9.25, June 29, 2017.
- Morrison, CD, Allington, TM, Thompson, CL, Gilmore, HL, Chang, JD, Keri, RA and Schiemann, WP. (2016) Abl kinase inhibits breast cancer tumorigenesis through reactivation of p53-mediated p21 expression. Oncotarget. 7:72777-72794.