EDUCATION & PROFESSIONAL TRAINING
- Post-Doctoral Training, Sphingolipids and Animal Models of Disease, Medical University of South Carolina
- Ph.D., Pharmacology and Toxicology, Washington State University
- B.S., Marine Biology, University of North Carolina at Wilmington
RESEARCH & INTERESTS
The long-term research goals of my lab are to define the roles of lipid metabolic pathways centered on bioactive sphingolipids in intestinal biology and pathobiology and determine the mechanisms involved.
Sphingolipids, long thought to be only structural components of cell membranes, have emerged over the last two decades as bioactive lipids with distinct and important biological functions. Fatty acids are incorporated into ceramide, the central lipid in sphingolipid metabolism, via two enzymatic reactions: through de novo synthesis initiated by serine palmitoyl transferase (SPT) into the sphingoid backbone of sphingolipids, and via incorporation by ceramide synthases (CerS) into the fatty-acyl chain of ceramide. Ceramide in turn serves as a metabolic hub for the synthesis of several classes of sphingolipids, including sphingomyelin, ceramide 1-phosphate (C1P), glycosphingolipids and sphingosine-1-phosphate (S1P). We have previously demonstrated the importance of serval sphingolipids and their metabolic enzymes as key regulators in inflammatory bowel disease, as well as colon cancer and colitis-associated colon cancer. In addition, we have demonstrated that specific dietary FAs increase inflammation in the intestinal epithelium in cells and in vivo.
Our current research focus builds on this foundation.
The three main projects in my lab examine:
- Effects of dietary fatty acids on sphingolipid metabolism in ER stress and inflammation.
- Roles of dietary fatty acids and sphingolipids in animal models of inflammation and colitis-associated cancer.
- Roles for sphingolipids and their metabolizing enzymes in intestinal biology and pathobiology.
In our pursuits, we utilize cell lines, intestinal organoids (murine and human), mouse models, patient derived xenografts, and biobanked samples from patients with IBD and colorectal cancer to determine the effects of high fat diets and dietary fatty acids on sphingolipid metabolism and intestinal pathobiology. Moreover, we utilize unbiased “Omics” approaches in our research efforts, specifically lipidomics, proteomics and phospho-proteomics, in order to define novel mechanisms, interventions, therapeutic targets and biomarkers for intestinal pathobiologies.
- Choi S, Snider JM, Cariello, CP, Lamber JM, Anderson AK, Cowart LA, Snider AJ. Sphingosine kinase 1 is required for myristate-induced TNFα expression in intestinal epithelial cells. 2020 POLM Jan 29:106423. doi: 10.1016/j.prostaglandins.2020.106423. [Epub ahead of print]. PMID: 32006664. PMCID: in process.
- Choi S, Snider JM, Olakkengil N, Lambert JM, Anderson AK, Ross-Evans JS, Cowart LA, Snider AJ. Myristate-induced endoplasmic reticulum stress requires ceramide synthases 5/6 and generation of C14-ceramide in intestinal epithelial cell. FASEB J. 2018 Oct;32(10):5724-5736. PMID: 29768040; PMCID: PMC6133702.
- Espaillat MP, Snider AJ*, Qiu Z, Channer B, Coant N, Schuchman EH, Kew RR, Sheridan BS, Hannun YA, Obeid LM. Loss of acid ceramidase in myeloid cells suppresses intestinal neutrophil recruitment. FASEB J. 2018; 32(5): 2339-2353. PMID: 29259036; PMCID: PMC6207279. *Denotes co-corresponding.
- Pulkoski-Gross MJ, Uys JD, Orr-Gandy KA, Coant N, Bialkowska AB, Szulc M, Bai A, Bielawska A, Townsend DM, Hannun YA, Obeid LM, Snider AJ. Novel sphingosine kinase-1 inhibitor, LCL351, reduces immune responses in murine DSS-induce colitis. POLM. 2017 Apr 2;130:47-56. PMID: 28377281; PMCID: PMC5509055.
- Senkal CE, Salama MF, Snider AJ, Allopenna JJ, Rana NA, Koller A, Hannun YA, Obeid LM. Ceramide is metabolized to acylceramide and stored in lipid droplets. Cell Metab. 2017 Mar;25(3)686-697. PMID: 28273483; PMCID: PMC5472424.
- García-Barros M, Coant N, Kawamori T, Wada M, Snider AJ, Truman JP, Wu BX, Furuya H, Clarke CJ, Bialkowska AB, Ghaleb A, Yang VW, Obeid LM, Hannun YA. Role of neutral ceramidase in colon cancer. FASEB J. 2016 Dec; 30(12);4159-4171. PMID: 27609772; PMCID: PMC5102116.
- Wang K, Xu R, Snider AJ, Schrandt J, Li Y, Bialkowska AB, Li M, Zhou J, Hannun YA, Obeid LM, Yang VW, Mao C., Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system. Cell Death Dis., 2016 Mar 3;7:e2124. PMID: 26938296; PMCID: PMC4823937.
- Ghaleb AM, Bialkowska AB, Snider AJ, Gnatenko DV, Hannun YA, Yang VW, Schmidt VA. IQ motif-containing GTPase-activating protein 2 (IQGAP2) is a novel regulator of colonic inflammation in mice. PLos One. 2015 Jun 5;10(6):e0129314. PMID: 26047140; PMCID: PMC4457730.
- Snider AJ*, Ali WH, Sticca JA, Coant N, Ghaleb AM, Kawamori T, Yang VW, Hannun YA, Obeid LM. Distinct roles for hematopoietic and extra-hematopoietic sphingosine kinase-1 in inflammatory bowel disease. PLoS One. 2014;9(12):e113998. PMID: 25460165; PMCID: PMC4252067. *first and corresponding author.
- Snider AJ, Wu B, Jenkins RW, Sticca JA, Kawamori T, Hannun YA, Obeid LM. Loss of neutral ceramidase increases inflammation in a mouse model of inflammatory bowel disease. POLM. 2012 Dec; 99(3-4): 124-30. PMID: 22940715; PMCID: PMC3661865.
- Jenkins RW, Clarke CJ, Canals DN, Snider AJ, Gault CR, Heffernan-Stroud L, Wu BX, Simbari F, Roddy P, Kitatani K, Obeid LM, Hannun YA. Regulation of CC ligand 5/RANTES by acid sphingomyelinase and acid ceramidase. J Biol Chem. 2011; 286(15): 13292-303. PMID: 2133555; PMCID: PMC3075676.
- Snider AJ, Kawamori T, Bradshaw SG, Orr KA, Gilkeson GS, Hannun YA, Obeid LM. A role for sphingosine kinase 1 in dextran sulfate sodium-induced colitis. FASEB J. 2009; 23(1): 143-52. PMID: 18815359; PMCID: PMC2626622.