My research 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, my lab works on delineating the roles of PI3K and TGF??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 my lab are: (1) We were among the firsts to develop multiple genetically engineered mouse models (GEMMs) of HNSCC in both PI3K and TGFß 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
Qiu Y, Qi Z, Wang Z, Cao Y, Lu L, Zhang H, Mathes D, Pomfret EA, Lu SL, Wang Z. EGF-IL2 bispecific and bivalent EGF fusion toxin efficacy against syngeneic head and neck cancer mouse models. Oncol Rep. 2023 Feb;49(2). PubMed PMID: 36579667
Jiang H, Suo H, Gao L, Liu Y, Chen B, Lu SL, Jin F, Cao Y. Metformin plays an antitumor role by downregulating inhibitory cells and immune checkpoint molecules while activating protective immune responses in breast cancer. International Immunopharmacology, 118: 110038 (2023)
Lu L, Qiu Y, Espinoza E, Gerndt S, Lu A, Allen A, Gao D, Harry B, Gross N, Song J, Bornstein S, Zevallos J, Lu SL: Validation of a saliva-liquid biopsy test (HNKlear) for head and neck squamous cell carcinoma. S008, JAMA Network for the proceedings of the AHNS 11th International Conference on Head and Neck Cancer.
Frank D, Qiu Y, Cao Y, Zhang S, Lu L, Kofonow J, Roberson C, Liu Y, Wang H, Levens C, Kuhn K, Song J, Ramakrishnan V, Lu SL: A dysbiotic microbiome promotes head and neck squamous cell carcinoma. Oncogene, 41, 1269-1280 (2022).
Qiu Y, Lu L, Halven A, Terrio R, Yuldelson S, Dougal N, Galbo F, Lu A, Gao D, Blomquist B, Zevallos J, Harry B, Yao X, Lu SL: COVIDFastTM: A high-throughput and RNA extraction-free method for SARS-CoV-2 detection in swab (SwabFASTTM) or saliva (SalivaFASTTM).
medRxiv (2022); doi: https://doi.org/10.1101/2021.12.29.21268527
Frank D, Magno J, Velasco K, Bootpetch T, Salud J, David K, Yee E, Dulnuan H, Lacuata J, Arbizo J, Guce B, Mendoza K, Illustre G, Kofonow J, Chiong A, Roberson R, Tongol E, Sacayan N, Lu SL, Yarza T, Chiong C, Santos-Cortez R: Microbiota associated with cholesteatoma tissue in chronic suppurative otitis media. Frontiers in Cellular and Infection Microbiology, 12: 746428 (2022)
Qi Z, Qiu Y, Wang Z, Zhang H, Lu L, Liu Y, Mathes D, Pomfret E, Gao D, Lu SL*, Wang Z: A novel diphtheria toxin-based bivalent human EGF fusion toxin for treatment of head and neck squamous cell carcinoma. Molecular Oncology, 15: 1054-1068 (2021).
Qiu Y, Lu L, Gao D, McGrath P, Han C, Kogut I, Blomquist B, Yao X, Zevallos J, Harry B, Lu SL: SARS-Cov-2 viral load monitoring by extraction-free testing of saliva. medRxiv 2021.08.02.21261502; doi: https://doi.org/10.1101/2021.08.02.21261502
Qiu Y, Lu L, Halven A, Terrio R, Yuldelson S, Dougal N, Galbo F, Lu A, Gao D, Blomquist B, Zevallos J, Harry B, Yao X, Lu SL: COVIDFastTM: A high-throughput and RNA extraction-free method for SARS-CoV-2 detection in swab (SwabFASTTM) or saliva (SalivaFASTTM). medRxiv 2021.12.29.21268527; doi: https://doi.org/10.1101/2021.12.29.21268527
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
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 enriching and maintaining of cancer stem cells in head and neck squamous cell carcinoma. Molecular Oncology, 14: 139-158 (2020)
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, Feng Y, Gao L, Li X, Jin Q, Wang Y, Xu Y, Jin F, Lu SL*, Wei M: Artemisinin enhances the anti-tumor immune response in 4T1 breast cancer cells in vitro and in vivo. International Immunopharmacology, 70: 110-116 (2019)
Lu SL, Hsu FM, Tsai CL, Lee JM, Huang PM, Hsu CH, Lin CC, Chang YL, Hsieh MS, Cheng JC. Improved prognosis with induction chemotherapy in pathological complete responders after trimodality treatment for esophageal squamous cell carcinoma: Hypothesis generating for adjuvant treatment. Eur J Surg Oncol. 2019 Aug;45(8):1498-1504. PubMed PMID: 30910457
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). PMCID: PMC5883341
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). PMCID: PMC6031150
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
Malkoski SP, Cleaver TG, Thompson JJ, Sutton WP, Haeger SM, Rodriguez KJ, Lu SL, Merrick D, Wang XJ. Role of PTEN in Basal Cell Derived Lung Carcinogenesis. Mol Carcinog. 2013 Apr 26. [Epub ahead of print] PubMed PMID: 23625632
Du L, Chen X, Shen J, Zhang F, Lu SL: PIK3CA overexpression induces epithelial-mesenchymal transition and progression of head and neck squamous cell carcinoma. Annual Meeting of American Association of Cancer Research. Washington DC, 2013
Du L, Shen J, Weems A, and Lu SL*: Role of phosphatidylinositol-3-kinase pathway in head and neck squamous cell carcinoma. J Oncol in press (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 Oncol 48: 73-8 (2012)
Lu SL:Role of DNA repair in head and neck cancer in [DNA repair] ed by Francesca Storici. Intech
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. Int. J Oncol 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).
Qi Z, Qiu Y, Wang Z, Zhang H, Lu L, Liu Y, Mathes D, Pomfret E, Gao D, Lu SL*, Wang Z: A novel bivalent diphtheria toxin-based human EGF fusion immunotoxin for treatment of head and neck squamous cell carcinoma. Molecular Oncology,
Frank D, Qiu Y, Cao Y, Zhang S, Lu L, Kofonow J, Roberson C, Liu Y, Wang H, Levens C, Kuhn K, Song J, Ramakrishnan V, Lu SL: A dysbiotic microbiome promotes head and neck squamous cell carcinoma. Oncogene, 2021, in press
Qiu Y, Qi Z, Wang Z, Cao Y, Lu L, Zhang H, Mathes D, Pomfret E, Lu SL*, Wang ZR: EGF-IL2 bispecific and bivalent EGF fusion toxin efficacy against syngenic head and neck cancer mouse models. Oncology Reports Epub (2022) *=co-corresponding author
Saliva liquid biopsy for head and neck cancer. In [Emerging Technologies for Cancer Detection and Diagnosis] eds. Miguel Ossandon, Ben Prickril, Avraham Rasooly. Tyler & Francis, 2024