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Abraham Schneider, DDS, Ph.D

Associate Professor

Oncology and Diagnostic Sciences

mission

The research in my laboratory is currently focused on gaining a better understanding of the potential use of antidiabetic biguanides, such as metformin, in oral cancer chemoprevention and treatment. In the United States, roughly one person dies every hour of each day because of complications associated with oral cancer. Unfortunately, improvements in oral cancer patient survival rates have remained unchanged for decades. Late diagnosis and “field cancerization” with multifocal potentially malignant dysplastic lesions or secondary primary tumors are major factors compromising standard treatments. In this regard, long-term chemopreventive targeting of “at risk” oral premalignant lesions may offer a great opportunity to control tumor development and progression. We recently reported that metformin, a FDA-approved biguanide used as first-line treatment for type 2 diabetes, significantly prevented the conversion of carcinogen-induced oral premalignant lesions into malignant tumors in mice. Our results also point to the organic cation transporter-3 (OCT-3) as facilitator of metformin uptake and intracellular activity in oral carcinogenesis. The significance of these studies stands on the potential to define largely unexplored mechanisms of biguanide uptake and activity in oral oncology, and eventually use OCT-3 as a potential tumor biomarker to predict sensitivity or resistance to metformin in the clinical setting. Our ultimate goal is to make an impact on patients who could benefit from biguanides as novel agents in oral cancer chemoprevention and treatment.

PUBLICATIONS:

Schneider A, JM Taboas, LK McCauley and PH Krebsbach. Skeletal homeostasis in tissue-engineered bone. J Orthop Res 21(5): 859-864, 2003.

Kalikin LM, A Schneider, MA Thakur, Y Fridman, LB Griffin, RL Dunn, TJ Rosol, RB Shah, A Rehemtulla, LK McCauley and KJ Pienta. In vivo visualization of metastatic prostate cancer and quantitation of disease progression in immunocompromised mice. Cancer Biol Ther 2 (6): 17-21, 2003.

McCauley LK and A Schneider. PTHrP and skeletal metastasis. Cancer Treat Res 118: 125-147, 2004.

Sun YX, A Schneider, Y Jung, J Wang, J Dai, J Wang, K Cook, NI Osman, AJ Koh-Paige, H Shim, KJ Pienta, ET Keller, LK McCauley and RS Taichman. Skeletal localization and neutralization of the SDF-1 (CXCL12)/CXCR4 axis blocks prostate cancer metastasis and growth in osseous sites in vivo. J Bone Miner Res 20(2):318-329, 2005.

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.

Pettway GJ, A Schneider, AJ Koh, E Widjaja, MD Morris, JA Meganck, SA Goldstein and LK McCauley. Anabolic actions of PTH (1-34): Use of a novel tissue engineering model to investigate temporal effects on bone. Bone 36(6):959-70, 2005

Liao J, A Schneider, N Datta and LK McCauley. Extracellular calcium as a candidate mediator of prostate cancer skeletal metastasis. Cancer Res 66(18): 9065-9073, 2006.

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. Neoplasia 10(11): 1295-1302, 2008.

Hagner PR, A Schneider, RB Gartenhaus. Targeting the translational machinery as a novel treatment for hematologic malignancies. Blood 115(11): 2127-35,2010.

Wang X and Schneider A, HIF2alpha-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.

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 carcinogen-induced premalignant lesions. Cancer Prevention Research 5(4): 562-73, 2012.

Patel H, RH Younis, RA Ord, JR Basile and A 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

EDUCATION AND TRAINING:

  • Dental Degree: Peruvian University Cayetano Heredia
  • Doctoral Degree: University of Michigan
  • Fellowship: National Institute of Dental and Craniofacial Research, NIH