Maria Hernandez-Corbacho

imageSenior Research Support Specialist

Education: 
Bachelor’s Degree in Chemistry at the University of Barcelona, Spain (2000).
Bachelor’s Degree in Biochemistry at the University of Barcelona, Spain (2003).

Contact Information:
MART Bldg., Floor 9S
Email:  maria.hernandez@stonybrookmedicine.edu

Project:

The essential role of ceramide during cell death has been extensively studied in the last decades. For the first time, Obeid et al. demonstrated that exogenous ceramide (Cer) treatment induced apoptosis in leukemic cells. Ceramide synthase (CerS)-mediated Cer formation has been proven to play a role in cancer cell biology such as chemotherapy (cisplatin, doxorubicin, paclitaxel,…) or IR-induced cell death. Conversely, upregulation of enzymes involved in the catabolism of Cer or its conversion to more complex sphingolipids, such as the glucosylceramide synthase (GCS) enzyme or the ceramide transporter CERT, have been associated to multidrug resistance in cancer cells.

Our group has recently found that a long chain fatty acyl CoA synthetase (ACSL5) and acyl-CoA:diacylglycerol acyltransferase (DGAT2) interact with CerS, which results in the synthesis of O-acylceramide (O-acylCer) from Cer and fatty acyl-coA (FA-CoA). Inhibition of O-acylCer formation sensitize HCT-116 cells to 5-FU. DGAT acyl-CoA:diacylglycerol acyltransferase (DGAT) enzyme catalyze the last reaction of the triacylglycerol (TAG) synthesis from diacylglycerol (DAG) and FA-CoA (10), which are then stored in the lipid droplets (LDs). In addition, several lines of evidences have associated upregulation of lipid metabolism, such as TAG synthesis and LDs accumulation, with cancer biology, including cell proliferation, cancer tumorigenicity, stemness, and chemotherapy resistance. Furthermore, expression of Dgat1 and Dgat2 genes are dysregulated in many cancers. DGAT2 is highly expressed in liver, breast, thyroid, prostate and pancreatic cancers. Nevertheless, the specific role of DGAT2 and O-acylCer formation in cancer biology remains very poorly explored.

In the present, my main focus is to investigate the role of DGAT2 as a new therapeutic target in the treatment of breast cancer. We have found that PF-06424439 compound, a specific inhibitor of DGAT2 enzyme, enhances the effects of chemotherapy. When breast cancer cells were treated with the combination of chemotherapy and PF-06424439 Cers levels were increased beyond those of chemotherapy alone. Furthermore, apoptosis was also increased in the co-treatment group. These observations will hopefully lead to future preclinical and clinical studies on targeting DGATs as potential novel approaches to cancer chemotherapy.   

Publications

1: Siskind LJ, Mullen TD, Romero Rosales K, Clarke CJ, Hernandez-Corbacho MJ, Edinger AL, Obeid LM (2010) The BCL-2 protein BAK is required for long-chain ceramide generation during apoptosis. J Biol Chem.

2: Canals D, Jenkins RW, Roddy P, Hernández-Corbacho MJ, Obeid LM, Hannun YA (2010) Differential effects of ceramide and sphingosine-1-phosphate on ERM phosphorylation: probing sphingolipid signaling at the outer plasma membrane. J Biol Chem.

3: María José Hernández-Corbacho, Russell W. Jenkins, Christopher J. Clarke, Yusuf A. Hannun, Lina M. Obeid, Ashley J. Snider, and Leah J. Siskind (2011) Accumulation of Long-Chain Glycosphingolipids during Aging Is Prevented by Caloric Restriction. PloS One

4: Beverly LJ, Howell LA, Hernandez-Corbacho M, Casson L, Chipuk JE, Siskind LJ. (2013) BAK activation is necessary and sufficient to drive ceramide synthase-dependent ceramide accumulation following inhibition of BCL2-like proteins. Biochem J.

5: Nowling TK, Mather AR, Thiyagarajan T, Hernández-Corbacho MJ, Powers TW, Jones EE, Snider AJ, Oates JC, Drake RR, Siskind LJ. (2015) Renal glycosphingolipid metabolism is dysfunctional in lupus nephritis. J Am Soc Nephrol.

6: Adada MM, Canals D, Jeong N, Kelkar AD, Hernández-Corbacho M, Pulkoski-Gross MJ, Donaldson JC, Hannun YA, Obeid LM. (2015) Intracellular sphingosine kinase 2-derived sphingosine-1-phosphate mediates epidermal growth factor-induced ezrin-radixin-moesin phosphorylation and cancer cell invasion. FASEB J.

7: Hernández-Corbacho MJ, Canals D, Adada MM, Liu M, Senkal CE, Yi JK, Mao C, Luberto C, Hannun YA, Obeid LM. (2015) Tumor Necrosis Factor-α (TNFα)-induced Ceramide Generation via Ceramide Synthases Regulates Loss of Focal Adhesion Kinase (FAK) and Programmed Cell Death. J Biol Chem.

8: Hernández-Corbacho MJ, Salama MF, Canals D, Senkal CE, Obeid LM. (2016) Sphingolipids in Mitochondria. Biochim Biophys Acta.

9: Dupre TV, Doll MA, Shah PP, Sharp CN, Siow D, Megyesi J, Shayman J, Bielwska A, Bielawski J, Beverly LJ, Hernández-Corbacho M, Clarke CJ, Snider AJ, Schnellmann RG, Obeid LM, Hannun YA, Siskind LJ. (2017) Inhibiting glucosylceramide synthase exacerbates cisplatin-induced acute kidney injury. J Lipid Res.

10: Hernández-Corbacho MJ, Obeid LM. (2019) A novel role for DGATs in cancer.  Adv Biol Regul.

11. Canals D, Salamone S, Santacreu BJ, Nemeth E, Aguilar D, Hernandez-Corbacho MJ, Adada M, Staquicini DI, Arap W, Pasqualini R, Haley J, Obeid LM, Hannun YA. (2020) Ceramide launches an acute anti-adhesion pro-migration cell signaling program in response to chemotherapy. FASEB J

12. Velazquez FN, Hernandez-Corbacho M, Trayssac M, Stith JL, Bonica J, Jean B, Pulkoski-Gross MJ, Carroll BL, Salama MF, Hannun YA, Snider AJ. (2020) Bioactive sphingolipids: Advancements and contributions from the laboratory of Dr. Lina M. Obeid.  Cell Signal.