AddressKarmanos Cancer Institute, 4100 John R, Detroit, MI 48201
Karmanos Cancer Institute
4100 John R, Room 640
Detroit, MI 48201
DepartmentDepartment of Pathology & Department of Oncology
• Prostate cancer, lung cancer, breast cancer, and esophageal-gastrointestinal junction carcinoma
• The molecular mechanisms underlying tumor cell phenotypic plasticity in tumor progression, metastasis and tumor response to host immune surveillance or drug treatment.
• Proteomic control by endogenous histone deacetylase inhibition
• Experimental cancer models with 3D culture, tumor xenografts in vivo and genetically modified mice
• Molecular diagnosis, prognosis and racial disparities in cancer
Dr. Sheng was one of the co-discovers of the tumor suppressor gene maspin, and she continues to be a leader in the maspin field. Dr. Sheng’s team approaches its research aspiration with innovative methodologies of biochemistry, molecular biology, cell biology, and animal models. The research in the Sheng Laboratory has been supported by a multidisciplinary ream of collaborators to explore the potential clinical translation in the areas of cancer diagnosis and prognosis, cancer clinical trials, as well as novel methods of drug delivery. The noteworthy breakthrough discoveries made by Dr. Sheng’s include: (i) maspin is an epithelial-specific protein and is essential for the maintenance of terminally differentiated epithelial phenotype, as maspin deficiency in mice leads to abnormal development and cancer in an epithelial-specific manner. Global maspin gene knockout leads to embryonic lethality; (ii) maspin acts as a serine protease inhibitor-like protein to inhibit the enzymatic activities of serine protease-like molecules including histone deacetylase 1 (HDAC1) and the zymogen of urokinase-type plasminogen activator (pro-uPA). By controlling the gene expression profile and stress response of epithelial cells, maspin averts the stemness of carcinoma cells and blocks tumor invasion and metastasis; (iii) maspin is differentially expressed in the progression of breast cancer, prostate cancer, lung cancer, oral squamous cell carcinoma and esophageal-gastrointestinal/esophageal junction adenocarcinoma. Dysregulation of both maspin expression and maspin subcellular localization contributes to cancer malignancy. Cytoplasmic retention of maspin in low grade tumors increases tumor cell immunogenicity, and can elicit tumor-eliminating immune response.
Dzinic SH, Mahdi Z, Bernardo MM, Vranic S, Beydoun H, Nahra N, Alijagic A, Harajli D, Pang A, Saligana DM, Rahman AM, Skenderi F, Hasanbegovic B, Dyson G, Beydoun R, and Sheng S. Maspin differential expression patterns as a marker for targeted screening of esophageal adenocarcinoma/gastroesophageal junction adenocarcinoma. PloS One 2019;14:e0215080.
Sheng S, Bernardo MM, Dzinic SH, Chen K, Heath EI and Sakr WA. Tackling tumor heterogeneity and phenotypic plasticity in cancer precision medicine: our experience and a literature review. Cancer Metastasis Rev 2018;37:655-63.
Dzinic SH, Bernardo MM, Li X, Fernandez-Valdivia R, Ho Y-S, Mi Q-S, Bandyopadhyay S, Lonardo F, Vranic S, Oliveira DSM, Bonfil DR, Dyson G, Chen K, Omerovic A, Sheng X, Han X, Wu D, Bi X, Cabaravdic D, Jakupovic U, Wahba M, Pang A, Harajli D, Sakr WA, and Sheng S. An Essential Role of Maspin in Embryogenesis and Tumor Suppression. Cancer Res. 2017;77:1–11.
Bernardo MM, Kaplun A, Dzinic SH, Li X, Irish J, Mujagic A, Jakupovic B, Back JB, Van Buren E, Han X, Dean I, Chen YQ, Heath E, Sakr W, and Sheng S. Maspin Expression in Prostate Tumor Cells Averts Stemness and Stratify Drug Sensitivity. Cancer Res 2015;75 3970-9.
Dzinic SH, Chen K, Thakur A, Kaplun A, Bonfil, RD, Li X, Liu J, Bernardo MM, Saliganan A, Back JB, Yano H, Schalk DL, Tomaszewski, EN, Beydoun AS, Dyson G, Mujagic A, Krass D, Dean I, Mi Q-S, Heath E, Sakr W, Lum LG, and Sheng S. Maspin Expression in Prostate Tumor Elicits Host Anti-tumor Immunity. Oncotarget 2014; 5:11225-36.
BS (1986): Beijing University, Beijing, China
PhD (1993): University of Florida College of Medicine, Gainesville, Florida
Post-Doc (1997): Dana-Farber Cancer Institute of Harvard Medical School, Boston, Massachusetts
CB7220 Molecular Biology of Cancer Development
CB7240 Cancer Therapy
CB7460 Cancer Signaling
CB7700 Cancer Biology Program Graduate Student Journal Club