1. Dr. Bettaieb’ s research activities while pursuing a Ph.D. were focused on trying to uncover the molecular mechanism and cellular signaling of cancer cells death in response to noninvasive biological methods, such as hyperthermia. His work led to several quantitative experimental studies and increased our understanding of the biological effects of lethal hyperthermia as well as the adaptive survival responses (thermotolerance). As a first and main author, research findings were essential in uncovering ER stress as a potential molecular mechanism through which hyperthermia can cause cancer cells death. In this regard, hyperthermia could be useful in cancer therapy through regulating ER stress pathways in tumor cells.

1. Bettaieb A, Averill-Bates DA. Thermotolerance induced at a mild temperature of 40°C alleviates heat shock-induced ER stress and apoptosis in HeLa cells. Biochim Biophys Acta. 2015 Jan;1853(1):52-62. PubMed PMID: 25260982.

2. Glory A, Bettaieb A, Averill-Bates DA. Mild thermotolerance induced at 40 °C protects cells against hyperthermia-induced pro-apoptotic changes in Bcl-2 family proteins. Int J Hyperthermia. 2014 Nov;30(7):502-12. PubMed PMID: 25354679.

3. Bettaieb A, Averill-Bates DA. Thermotolerance induced at a fever temperature of 40 degrees C protects cells against hyperthermia-induced apoptosis mediated by death receptor signalling. Biochem Cell Biol. 2008 Dec;86(6):521-38. PubMed PMID: 19088800.

4. Bettaieb A, Averill-Bates DA. Thermotolerance induced at a mild temperature of 40 degrees C protects cells against heat shock-induced apoptosis. J Cell Physiol. 2005 Oct;205(1):47-57. PubMed PMID: 15887240.

 

2. Dr. Bettaieb’s tenure at the University of California-Davis was very productive. He achieved several breakthroughs that enhanced our understanding of metabolic regulation. While at UC-Davis, Dr. Bettaieb’s research activities were focused on addressing the metabolic and non-metabolic functions of protein tyrosine phosphatases, namely PTP1B, TCPTP and SHP2, and soluble epoxide hydrolase (sEH). Using combined genetic, biochemical, molecular, and mass spectroscopy approaches, He identified new physiological substrates for PTP1B in the adipose and pancreas tissues and provided new mechanistic and functional insights into the role of PTP1B in obesity, Type 2 diabetes, and acute pancreatitis. Similarly, Dr. Bettaieb’s research addressed the physiological role of hepatic Shp2 using liver-specific deletion and demonstrated that liver-specific Shp2 deficient mice gained less weight and exhibited increased energy expenditure compared with controls. In addition, hepatic Shp2 deficiency led to decreased liver steatosis and prevented the development of insulin resistance following high fat feeding. These studies identified hepatic Shp2 as a novel regulator of systemic energy balance. Furthermore, Dr. Bettaieb investigated the endocrine and exocrine functions of TCPTP using pancreas-specific deletion and demonstrated that pancreatic TCPTP deficiency mitigated acute pancreatitis in mice and affected pancreatic beta cell function and insulin secretion.

1. Xi Y, Liu S, Bettaieb A, Matsuo K, Matsuo I, Hosein E, Chahed S, Wiede F, Zhang S, Zhang ZY, Kulkarni RN, Tiganis T, Haj FG. Pancreatic T cell protein-tyrosine phosphatase deficiency affects beta cell function in mice. Diabetologia. 2015 Jan;58(1):122-31. PubMed PMID: 25338551; PubMed Central PMCID: PMC4258175.

2. Bettaieb A, Xi Y, Hosein E, Coggins N, Bachaalany S, Wiede F, Perez S, Griffey SM, Sastre J, Tiganis T, Haj FG. Pancreatic T cell protein-tyrosine phosphatase deficiency ameliorates cerulein-induced acute pancreatitis. Cell Commun Signal. 2014 Mar 10;12:13. PubMed PMID: 24606867; PubMed Central PMCID: PMC4016516.

3. Nagata N, Matsuo K, Bettaieb A, Bakke J, Matsuo I, Graham J, Xi Y, Liu S, Tomilov A, Tomilova N, Gray S, Jung DY, Ramsey JJ, Kim JK, Cortopassi G, Havel PJ, Haj FG. Hepatic Src homology phosphatase 2 regulates energy balance in mice. Endocrinology. 2012 Jul;153(7):3158-69. PubMed PMID: 22619361; PubMed Central PMCID: PMC3380313.

4. Matsuo K, Bettaieb A, Nagata N, Matsuo I, Keilhack H, Haj FG. Regulation of brown fat adipogenesis by protein tyrosine phosphatase 1B. PLoS One. 2011 Jan 31;6(1):e16446. PubMed PMID: 21305007; PubMed Central PMCID: PMC3031545.

 

3. As an independent investigator and in collaboration with Dr. Bruce Hammock (University of California Davis) Dr. Bettaieb led several projects studying the metabolic and non-metabolic functions of soluble epoxide hydrolase (sEH). Using genetic, pharmacological, biochemical, and metabolomics approaches he demonstrate that sEH deficiency and pharmacological inhibition prevents and alleviates obesity and its associated metabolic dysregulation, improves glucose tolerance, reduces pain-related behavior, regulates endoplasmic reticulum stress and fibrosis, and attenuates acute pancreatitis. These studies provided new insights into sEH metabolic functions and the molecular mechanisms mediating its actions. Notably, attenuation of pain by sEH pharmacological inhibition is being tested for human therapeutic intervention and the initial results are promising

1. Inceoglu B, Bettaieb A, Trindade da Silva CA, Lee KS, Haj FG, Hammock BD. Endoplasmic reticulum stress in the peripheral nervous system is a significant driver of neuropathic pain. Proc Natl Acad Sci U S A. 2015 Jul 21;112(29):9082-7. PubMed PMID: 26150506; PubMed Central PMCID: PMC4517273.

2. Bettaieb A, Morisseau C, Hammock B, Haj F. Soluble epoxide hydrolase deficiency ameliorates acute pancreatitis in mice. Free Radic Biol Med. 2014 Oct;75 Suppl 1:S32. PubMed PMID: 26461340.

3. Bettaieb A, Nagata N, AbouBechara D, Chahed S, Morisseau C, Hammock BD, Haj FG. Soluble epoxide hydrolase deficiency or inhibition attenuates diet-induced endoplasmic reticulum stress in liver and adipose tissue. J Biol Chem. 2013 May 17;288(20):14189-99. PubMed PMID: 23576437; PubMed Central PMCID: PMC3656275.

4. Inceoglu B, Wagner KM, Yang J, Bettaieb A, Schebb NH, Hwang SH, Morisseau C, Haj FG, Hammock BD. Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of type I diabetes. Proc Natl Acad Sci U S A. 2012 Jul 10;109(28):11390-5. PubMed PMID: 22733772; PubMed Central PMCID: PMC3396532.

 

4. Diet can play a significant role in preventing the metabolic syndrome and its associated pathologies. In collaboration with Dr. P. Oteiza (University of California Davis), Dr. Bettaieb investigated the effects of flavan-3-ol (−)-epicatechin (EC), the most abundant flavonoid in the human diet, on metabolic regulation. The team demonstrated that EC prevented TNFa-induced activation of signaling cascades that led to inflammation and insulin resistance in adipocytes. They also found that EC supplementation to the diet mitigated high fructose-induced insulin resistance in rodents by modulating redox signaling and ER stress response in adipose and liver tissues.

1. Bettaieb A, Cremonini E, Kang H, Kang J, Haj FG, Oteiza PI. Anti-inflammatory actions of (-)-epicatechin in the adipose tissue of obese mice. Int J Biochem Cell Biol. 2016 Dec;81(Pt B):383-392. PubMed PMID: 27592457.

2. Cremonini E, Bettaieb A, Haj FG, Fraga CG, Oteiza PI. (-)-Epicatechin improves insulin sensitivity in high fat diet-fed mice. Arch Biochem Biophys. 2016 Jun 1;599:13-21. PubMed PMID: 26968772.

3. Vazquez Prieto MA, Bettaieb A, Rodriguez Lanzi C, Soto VC, Perdicaro DJ, Galmarini CR, Haj FG, Miatello RM, Oteiza PI. Catechin and quercetin attenuate adipose inflammation in fructose-fed rats and 3T3-L1 adipocytes. Mol Nutr Food Res. 2015 Apr;59(4):622-33. PubMed PMID: 25620282; PubMed Central PMCID: PMC4408935.

4. Bettaieb A, Vazquez Prieto MA, Rodriguez Lanzi C, Miatello RM, Haj FG, Fraga CG, Oteiza PI. (-)-Epicatechin mitigates high-fructose-associated insulin resistance by modulating redox signaling and endoplasmic reticulum stress. Free Radic Biol Med. 2014 Jul;72:247-56. PubMed PMID: 24746618; PubMed Central PMCID: PMC4077617. **

 

Complete List of Published Work in My Bibliography:
https://www.ncbi.nlm.nih.gov/myncbi/16o7gUz8_0CQn/bibliography/public/