Associate Professor Abraham Schneider, DDS, PhD
The Schneider laboratory is conducting basic and translational research to gain insight into the potential repurposing of biguanide compounds within local delivery formulations for dental, oral and craniofacial applications. Through cross-disciplinary collaborations with faculty at the University of Maryland School of Dentistry, we are developing novel metformin-containing bioactive materials to enhance the repair and regeneration of mineralized tissue including dentin and bone. Our studies are particularly focused on the role played in these processes by the AMP-activated protein kinase (AMPK) signaling pathway, a master sensing mechanism of cellular bioenergetics. We envision our results will yield valuable information to ultimately implement metformin-containing formulations in the treatment of prevalent diseases affecting dental, oral and craniofacial tissues including dental caries, periodontal bone loss and oral cancer. Another area of interest in the Schneider lab is to investigate whether pro-oncogenic intracellular signals depend on the function of metabolic mediators to promote or accelerate the progression of oral potentially malignant disorders to oral squamous cell carcinoma (OSCC). These efforts are currently centered on elucidating the role of fatty acid synthase (FASN), a key de novo lipogenic enzyme known to be overexpressed in OSCC and associated with poor patient survival, on epidermal growth factor receptor (EGFR) activation. We have found that oral dysplastic keratinocytes become more motile and potentially invasive when exposed to glucose-rich microenvironments or nicotine. These cellular responses, critical in the progression of oral cancer, are triggered by FASN-mediated EGFR activation. These novel findings suggest that FASN may act as a targetable metabolic regulator of EGFR signaling in oral potentially malignant disorders.
Cancer Biology and Experimental Therapeutics
- Wisniewski DJ, T Ma and A Schneider. Fatty Acid Synthase mediates high glucose-induced EGFR activation in oral dysplastic keratinocytes. J Oral Pathol Med, 50(9): 919-926, 2021. PMID: 34402100.
- Wisniewski DJ, T Ma and A Schneider. Nicotine induces oral dysplastic keratinocyte migration via Fatty Acid Synthase-dependent Epidermal Growth Factor Receptor activation. Experimental Cell Research 370(2): 343-352, 2018. PMID: 29966661
- Wisniewski DJ, T Ma and A Schneider. Advances in the chemopreventive targeting of oral carcinogenesis. Current Oral Health Reports 2(2): 63-72, 2015.
- Schneider A. Mouse models to study metformin effects in carcinogenesis. In: Berger NA (ed) Murine Models, Energy Balance and Cancer. Energy Balance and Cancer 10: 271-292, 2015. Springer International Publishing, Switzerland.
- Patel H, RH Younis, RA Ord, JR Basile andA Schneider. Differential expression of organic cation transporter OCT-3 in oral premalignant and malignant lesions: potential implications in the antineoplastic effects of metformin. J Oral Pathol Med 42(3):250-6, 2013. PMID: 22861817
- Vitale-Cross L, AA Molinolo, D Martin, RH Younis, M Takashi, V Patel, W Chen,A Schneider* and JS Gutkind. Metformin prevents the development of oral squamous cell carcinomas from carcinogenesis induced premalignant lesions. Cancer Prev Res 5(4): 562-73, 2012. PMID: 22467081. *Co-senior corresponding author
- Wang X, A Schneider. HIF2a-mediated activation of the Epidermal Growth Factor Receptor potentiates head and neck cancer cell migration in response to hypoxia. Carcinogenesis 31(7): 1202-10, 2010. PMID: 20395290
- Schneider A, RH Younis and JS Gutkind. Hypoxia-induced energy stress inhibits the mTOR pathway by activating an AMPK/REDD1 signaling axis in head and neck squamous cell carcinoma. Neoplasia10(11):1295-1302, 2008. PMID: 18953439
- Schneider A, LM Kalikin, AC Mattos, ET Keller, MJ Allen, KJ Pienta and LK McCauley. Bone turnover mediates preferential localization of prostate cancer in the skeleton. Endocrinology 146 (4): 1727-1736, 2005. PMID: 15637291
- McCauley LK and A Schneider. PTHrP and skeletal metastasis. Cancer Treatment and Research 118: 125-147, 2004. PMID: 15043191
Stem cell-based mineralized tissue regeneration
- Wang S, Y Xia, T Ma, MD Weir, K Ren, MA Reynolds, Y Shu, L Cheng, A Schneider*,Hockin H. K. Xu. Novel metformin-containing resin promotes odontogenic differentiation and mineral synthesis of dental pulp stem cells. Drug Delivery and Translational Research 9(1): 85-96, 2019. PMID: 30465181. *Co-senior corresponding author.
- Qin W, J-Y Chen, J Guo, T Ma, MD Weir, D Guo, Y Shu, Z-M Lin, A Schneider*and HHK Xu. Novel calcium phosphate cement with metformin-loaded chitosan for odontogenic differentiation of human dental pulp cells. Stem Cells Int, 2018: 7173481. PMID: 30598667 *Co-senior corresponding author.
- Al Jofi FE, T Ma, D Guo, MP Schneider, Y Shu, HHK Xu, and A Schneider.Functional Organic Cation Transporters Mediate Osteogenic Response to Metformin in Human Umbilical Cord Mesenchymal Stromal Cells. Cytotherapy 20(5): 650-659, 2018. PMID: 29555409
- Qin W, X-L Gao, T Ma, MD Weir, J Zou, B Song, Z Lin, A Schneider*, and HHK Xu. Metformin enhances the differentiation of dental pulp stem cells into odontoblasts by activating AMPK signaling. Journal of Endodontics 44(4): 576-584, 2018. PMID: 29306537. *Co-senior corresponding author.
- Wang P, T Ma, K Hu, D Guo, Y Shu, HHK Xu, and A Schneider. Metformin induces osteoblastic differentiation of human induced pluripotent stem cell-derived mesenchymal stem cells. J Tissue Eng Regen Med 12(2): 437-446, 2018. PMID: 28494141
- Schneider A, JM Taboas, LK McCauley and PH Krebsbach. Skeletal homeostasis in tissue-engineered bone. Journal of Orthopaedic Research 21(5): 859-864, 2003. PMID: 12919874
Education and Training
DDS: Peruvian University Cayetano Heredia, Faculty of Stomatology, Lima - Peru.
Residency: Periodontics, University of Connecticut Health Center, Farmington, CT.
PhD: Oral Health Sciences, University of Michigan, Ann Arbor, MI.
Postdoctoral Fellowship: National Institute of Dental and Craniofacial Research, Bethesda, MD.