Barry J. Maurer, M.D. Ph.D.
M.D. - Wayne State University, Detroit, 1990
Ph.D. Chemical Biology - California Institute of Technology, Pasadena, 1990
Pediatric Hematology/Oncology Fellow -
Fred Hutchinson Cancer Research Center, Seattle, 1997
Department of Cell Biology and Biochemistry
Texas Tech University Health Sciences Center
3601 4th Street, Lubbock, TX 79430
Phone: (806) 743-2705
Laboratory and translational development of novel dihydroceramide-based chemotherapeutics driven by the cytotoxic retinoid, fenretinide (4-HPR). Basic laboratory investigation on sphingolipid pathway modulators; Phase 1 and Phase 2 trials in adult and pediatric oncology patients; dihydroceramide-induced cancer cell death mechanisms.
Fenretinide. We have developed new oral and intravenous formulations of fenretinide to increase tumor bed exposure and drive fenretinide-stimulated increases of cytotoxic dihydroceramide species in pediatric neuroblastoma and adult T-cell malignancies. Our phase I clinical trials have produced sustained complete responses in otherwise treatment-refractory patients. Based on these data, a Phase 2 study in relapsed adult peripheral T-cell lymphomas is opening in 2015.
Safingol. The L-threo stereochemical variant of normal D-erythro-sphinganine, safingol is incorporated into L-threo-dihydroceramides to produce multi-log synergy of fenretinide-induced cancer cell death in a wide variety of cancer cell types in vitro. Phase I trial of intravenous fenretinide + safingol in adult solid tumors and refractory lymphomas opening in 2015.
Targeted manipulation of dihydroceramide acyl chains. We have determined that not all dihydroceramide species are equally cytotoxic to all cancer cells. Exogenous supplementation of specific fatty acids can increase cellular production of the corresponding acyl-chained dihydroceramides to therapeutic advantage in a malignancy-specific manner. Modified fenretinide formulations to support clinical testing in development.
- Kang MH, Villablanca JG, Glade Bender JL, Matthay KK, Groshen S, Sposto R, Czarnecki S, Ames MM, Reynolds CP, Marachelian A, Maurer BJ. “Probable fatal drug interaction between intravenous fenretinide, ceftriaxone, and acetaminophen: a case report from a New Approaches to Neuroblastoma (NANT) Phase I study.” BMC Research Notes 7:256. doi: 10.1186/1756-0500-7-256 (2014). PubMed
- Holliday, Jr., M.W., Cox, S.B., Kang, M.H., and Maurer, B.J., “C22:0- and C24:0-dihydroceramides confer cytotoxicity in T-cell acute lymphoblastic leukemia cell lines.” PLoS ONE, 8(9): e74768. doi:10.1371/journal.pone.0074768 (2013). PubMed
- Maurer, B.J., Kang, M.H., Janeba, J., Groshen, S., Matthay, K.K., Sondel, P.M., Maris, J.M., Jackson, H.A., Goodzarian, F., Shimada, H., Villablanca, J.G., Czarnecki, S., Hasenauer, B., Reynolds, C.P., and Marachelian, A., “Phase I Trial of Fenretinide Delivered Orally in a Novel Organized Lipid Complex in Patients with Relapsed Neuroblastoma: A Report from the NANT Consortium.” Pediatr Blood Cancer, 60:1801-8 (2013). PubMed
- Shibina A, Seidel D, Somanchi SS, Lee DA, Stermann A, Maurer BJ, Lode HN, Reynolds CP, Huebener N. “Fenretinide sensitizes multidrug-resistant human neuroblastoma cells to antibody-independent and ch14.18-mediated NK cell cytotoxicity.” J Mol Med (Berl). 91:459-72 (2013). PubMed
- Cooper, J.P., Hwang, K., Singh, H., Wang, D., Reynolds, C.P., Curley Jr., R.C., Williams, S.C., Maurer, B.J., Kang, M.H., “Fenretinide Metabolism in Humans and Mice: Utilizing Pharmacologic Modulation of its Metabolic Pathway to Increase Systemic Exposure.” Br. J. Pharmacol. 163:1263-75 (2011). PubMed
- Kummar, S., Gutierrez, M.E., Maurer, B.J., Reynolds, C.P., Kang, M., Singh, H., Crandon, S., Murgo, A.J., Doroshow, J.H., “Phase I Trial of Fenretinide Lym-X-Sorb Oral Powder in Adults with Solid Tumors and Lymphomas.” Anticancer Res. 31:961-966 (2011). PubMed
- Lee, JS., Singh, H., Maurer B.J., Reynolds C.P., Kang M.H., “A validated LC with fluorescence detection method for simultaneous determination of safingol and D-erythro-sphinganine in human plasma.” Chromatographia. 71;1087-1091 (2010).
- Cheung E, Dorff T, Groshen S, Quinn DI, Reynolds, CP, Maurer B.J., Lara PN, Tsao-Wei DD, Twardowski P, Gandara DR, Chatta G, McNamara M, Pinski J: Oral fenretinide in biochemically recurrent prostate cancer: A California Cancer Consortium Phase II trial. Clinical Genitourinary Cancer 7:43-50 (2009). PubMed
- Kong, G., Wang, D., Wu, J., Konopleva, K., Andreeff, M., Ruvulo,P.P., and Maurer, B.J., “Synthetic Triterpinoid Cytotoxicity in Pediatric Acute Lymphoblastic Leukemia Cell Lines is Independent of Ceramide Increase but Synergized by N-(4-hydroxyphenyl)retinamide.” Leukemia, 22:1258-62, (2008). PubMed
- Wang, H., Maurer, B.J., Liu, Y-Y., Wang, E., Allegood, J., Kelly, S., Symolon, H., Liu, Y., Merrill Jr., A., Gouaze-Andersson, V. , Yu, J., Giuliano, A., Cabot, M.C.: “N-(4-hydroxyphenyl)retinamide Increases Dihydroceramide and Synergizes with Dimethylsphingosine to Enhance Cancer Cell Killing.” Mol Cancer Ther 7:2967-76. (2008). PubMed
- Maurer, B.J., Kalous, O., Yesair, D.W., Wu, X., Vratilova, J., Maldonado, V., Khankaldyyan, V., Frgala, T., Sun, B-C., McKee, R.T., Burgess, S.W., Shaw, W.A., and C. P. Reynolds, “Improved Oral Delivery of N-(4-hydroxyphenyl)retinamide with Novel LYM-X-SORB™ Organized Lipid Complex in Mice.” Clin Cancer Res. 13:3079-3086 (2007). PubMed
- Wu, X., Kim, Y., Sun, B-C., Moore, J.D., Shaw, W.A., and Maurer, B.J. “Liquid chromatography method for quantifying D-threo-1-Phenyl-2-palmitoylamino-3- morpholino-1-propanol (D-threo-PPMP) in mouse plasma and liver” J Chromatogr B 837(1-2):44-8 (2006). PubMed
- Batra, S., Reynolds, C.P., and Maurer, B.J., “Fenretinide Cytotoxicity for Ewing’s Sarcoma (ES) and Primitive Neuroectodermal Tumor (PNET) Cell Lines is Decreased by Hypoxia and Synergistically Enhanced by Ceramide Modulators.” Cancer Res 64:5415-5424 (2004). PubMed
- O’Donnell, P.H., Guo, W-X., Reynolds, C.P., and Maurer, B.J. “N-(4-hydroxyphenyl)- retinamide Increases Ceramide and Is Cytotoxic to Acute Lymphoblastic Leukemia Cell Lines, but Not to Non-Malignant Lymphocytes.” Leukemia 16:902-10 (2002). PubMed
- Wang, H., Maurer, B.J., Reynolds, C.P. and Cabot, M.C. “N-(4-Hydroxyphenyl)retinamide Elevates Ceramide in Neuroblastoma Cell Lines by Coordinate Activation of Serine Palmitoyltransferase and Ceramide Synthase.” Cancer Res 61:5102-5105 (2001). PubMed
- Maurer, B.J., Melton, L., Billups, C., Cabot, M.C., and Reynolds, C.P. “Synergistic Cytotoxicity in Solid Tumor Cell Lines Between N-(4-hydroxyphenyl)retinamide and Modulators of Ceramide Metabolism.” J Natl Cancer Inst 92:1897-1909 (2000). PubMed
- Maurer, B.J., Metelitsa, L.S., Seeger, R.C., Cabot, M.C., and Reynolds, C.P.: “N-(4-hydroxyphenyl)retinamide Increases Ceramide and Reactive Oxygen Species and Induces Mixed Apoptoses/Necrosis in Neuroblastoma Cell Lines.” J Nat Cancer Inst 91:1138-1146 (1999).