Shi-Long Lu, MD, PhD

Research Activities

Head and Neck Cancer Laboratory​​

Summary of the Lab's work
Our lab focuses on fundamental and translational aspects on head and neck cancers, including head and neck squamous cell carcinoma (HNSCC) and salivary gland tumors (SGTs). Specifically, our lab works on delineating the roles of PI3K and TGFb signaling pathway, cancer stem cell, and oral microbiome in HNSCC pathogenesis, identifying saliva biomarkers for early detection, recurrence, and surveillance of HNSCC, and developing novel therapeutic approaches for HNSCC. Several key discoveries from our lab are: (1) We were among the firsts to develop multiple genetically engineered mouse models (GEMMs) of HNSCC in both PI3K and TGFβ pathways. In combination with tobacco carcinogenesis protocol, these models develop HNSCC, which mimic human HNSCC etiologically, pathologically and molecularly. (2) We recently developed GEMMs for human SGTs, and are using these models to study the role of PTEN and Smad4 in SGT pathogenesis. (3) We have identified a panel of methylated genomic loci encoding microRNAs, which can be detected in patient saliva, to serve as biomarkers for early diagnosis, recurrence, and surveillance of HNSCC patients. (4). In collaboration with our colleague, we are among the firsts to study the functional role of oral microbiome in HNSCC pathogenesis and its impact on immunotherapy and PI3K targeted therapy. (5). In collaboration with our colleague, we are developing a novel therapeutic approach using an immunotoxin-based therapy on HNSCC models we have developed. 

Publications

• Chen X, Cao Y, Sedhom W, Lu L, Liu Y, Wang H, Oka M, Bornstein S, Said S, Song J, Lu SL. Distinct roles of PIK3CA in the enrichment and maintenance of cancer stem cells in head and neck squamous cell carcinoma. Mol Oncol. 2020 Jan;14(1):139-158. PubMed PMID: 31600013
• Yang CX, Sedhom W, Song J, Lu SL: The role of microRNAs in recurrence and metastasis of head and neck squamous cell carcinoma. Cancers, 11: 395  (2019)
• Cao Y, Liu H, Gao L, Lu L, Du L, Bai H, Li J, Said S, Wang X, Song J, Serkova N, Wei M, Xiao J, Lu SL: Cooperation between Pten and Smad4 in mouse salivary gland tumor formation and progression. Neoplasia, 20: 764-774 (2018).
• Cao Y, Green K, Quattlebaum S, Milam B, Lu L, Gao D, He H, Li N, Gao L, Hall F, Whinery M, Handley E, Ma Y, Jin F, Xiao J, Wei M, Smith D, Bornstein S, Gross N, Pyeon D, Song J, Lu SL: Methylated genomic loci encoding microRNAs in saliva as a biomarker panel in tissue and saliva for head and neck squamous cell carcinoma. Clinical Epigenetics, 10:43 (2018).
• Du L, Chen X, Cao Y, Lu L, Zhang F, Bornstein S, Li Y, Owens P, Malkoski S, Said S, Jin F, Kulesz-Martin M, Gross N, Wang XJ, Lu SL. Overexpression of PIK3CA in murine head and neck epithelium drives tumor invasion and metastasis through PDK1 and enhanced TGFß signaling. Oncogene. 2016 Sep 1;35(35):4641-52. PubMed PMID: 26876212
• Du L, Shen J, Weems A, Lu SL: Role of phosphatidylinositol-3-kinase pathway in head and neck squamous cell carcinoma. Journal of Oncology 450179 (2012).
• Minor J, Wang X, Zhang F, Song J, Jimeno A, Wang XJ, Lu X, Gross N, Kulesz-Martin M, Wang D, Lu SL: Methylation of microRNA-9 is a specific and sensitive biomarker for oral and oropharyngeal squamous cell carcinomas. Oral Oncology 48: 73-8 (2012).
• Lu SL: Cancer stem cells and head and neck squamous cell carcinomas. In [Stem Cells and Human Disease] eds. R. Srivastava and S. Shankar. Springer, pp. 497-507(2012)
• Weber S, Bornstein S, Li, Y, Malkoski S, Wang D, Rustgi A, Kulesz-Martin M, Wang XJ, Lu SL: Tobacco-specific carcinogen nitrosamine 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone induces AKT activation in head and neck epithelia. International Journal of Oncology 39:1193-1198 (2011).  
• Lu SL: DNA repair defects in head and neck cancer. In [DNA Repair and Human Health] ed. Sonya Vengrova. Intech,  pp. 373-384  (2011).