Chiara Luberto, PhD
Associate Professor
Department of Physiology and Biophysics,
Renaissance School of Medicine at Stony Brook University
Program Overview
Research in my lab focuses on regulation of sphingolipid signaling and the impact that its dysregulation might have on certain diseases, such as specific types of cancers. In particular, we focus on the study of the mammalian enzymes sphingomyelin synthases (SMS1 and SMS2) and their regulation of lipid mediated signaling through controlling the levels of ceramide and diacylglycerol (DAG). In fact, SMSs can directly regulate in opposing directions the levels of these two important bioactive lipids, which often exert opposing roles in the regulation of fundamental cellular functions such as protein trafficking/secretion, proliferation, differentiation and apoptosis.
The laboratory focuses on two main lines of research:
- The role of SMS1 and SMS2 in regulating DAG-mediated protein trafficking and secretion at the Trans Golgi Network (TGN) and the impact of such regulation on specific cargo molecules such as insulin and antimicrobial molecules.
- The role and function of SMS1 and SMS2 in the development and/or progression of cancer, in particular leukemias and lung cancer.
Lab Members
Etkin Akar
Senior Research Support Specialist
Education:
M.S Biological Sciences, Middle East Technical University(2023)
B.S Biological Sciences, Middle East Technical University(2020)
Maria Hernandez-Corbacho
Senior 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).
Project Description or Research Interest:
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.
Contact Info:
Phone: (631) 444-6064
maria.hernandez@stonybrookmedicine.edu
Yasharah Raza
PhD Student
Education:
Master’s (M.S) in Biomedical Sciences, Physiology and Biophysics [2017] Stony Brook University
Bachelor of Science (B.S.) in Biology, Neuroscience Specialization [2015] Stony Brook University Special Recognition: University Scholar
Graduate Program in Molecular and Cellular Pharmacology
Research Interest: Investigating the role and therapeutic potential of Sphingomyelin Synthase 1 (SMS1) in GATA1+ erythroid (M6) and megakaryocytic (M7) Acute Myeloid Leukemia (AML)
Contact Info:
yasharah.raza@stonybrook.edu
Guiqin Yu
Research Support Specialist
Education:
BS/MD in Medicine
Dept. of Cardiology of Kanazawa Medical University, Kanazawa, Japan
Contact Info:
gui.yu@stonybrook.edu