Targeting Lipid Rafts, Seeking Cures for Diseases Xin Wang* ACURE Biotechnology, Inc., Ellicott City, Maryland, USA

www.symbiosisonline.org Symbiosis www.symbiosisonlinepublishing.com

Editorial SOJ Microbiology & Infectious Diseases Open Access

Received: January 15, 2015; Accepted: January 22, 2015; Published: February 02, 2015

*Corresponding author: Xin Wang, ACURE Biotechnology, Inc., Ellicott City, Maryland, USA, Tel: 1-240-529-2819; E-mail: [email protected]

Editorial environmental risk factors to develop preventive medicine for leukemia. Lipid rafts are functional nanoscale microdomains enriched in The components and ratio of lipids species assembled into membrane in eukaryotic cells. Depending on anchored proteins biomembrane is another essential factor contributing to the cholesterol and sphingolipids, float in bilayer homogeneous lipids mutation models, we understood that the nature of biomembrane importantthrough Glycosylphosphatidylinositol physiological roles in particular (GPI), organs, or such other as lipidsbone arespecific very behaviors different of between lipid rafts. mammals From two and lipid Drosophila. metabolism Neutral- genes andtargeting blood, modification, cardiovascular, the microdomainsliver, brain etc. of through membrane intracellular play very

Ceramidase (N-CDase) nude mice do not have significant membrane trafficking,proteins anchoring cell signaling in lipid transduction rafts of cardiac and adaptation myocytes phenotype, even the N-CDase nude MEFs only show around 10% governto microenvironment. the electrical-impulse, For instance, regulate ionpolarizing channel of proteinscells, balance and knockoutweak cytotoxic is lethal toleration [4]. In addition, as compared the outcome to wild of typeimpairment MEFs byof metabolic resources, and stabilize the functional microdomains lipidFACS metabolism analysis (unpublished and membrane data), organization whereas Drosophila affects profoundly N-CDase between the actin cytoskeleton and extracellular matrix. Most different on survival and adaptation responses between mouse strategy in immunotherapy of cancer, diabetes, cardiovascular diseasesrecently, andtargeting Regenerative lipid rafts medicine modification for replacinghas become neuron a unified and and fly: most of Ceramide Transfer Protein (Cert) nude mice die human coronary artery smooth muscle cell. This editorial will from organogenetic defects at the stage of embryo 11. 5 days without any significant changes in fluidity of membrane [5]. Interesting enough, Cert nude flies fully develop to adulthood summarize my original research in past fifteen years. These are with around 35% increase of fluidity of membrane, 33% and the Myristoylationfoundation of ACURE and palmitoylation Biotechnology, areInc., twocompany. important co- 40% increase of cellular glucose and modification proteins, respectively,The biological which resulted aging is in the shorter most lifespan risk factor to flies for [6]. human diseases. The alteration of the lipid metabolism and cholesterol tyrosineand post-translational kinases are the modifications proteins with for both proteins N-myristoylation to target lipid and homeostasis contribute to cardiovascular diseases caused by rafts. G protein alpha subunits and a group of Src-related protein degeneration, and so on. Up to date, the most accepted events genepalmitoylation. having same A variety N-terminal of viral motif proteins in post such synaptic as Gag lipid proteins rafts aging of blood vessels, Alzheimer’s disease character by neuron also possess same modification. Luckily, we discovered a novel transportthat are demonstrated chains, all mainly to influence occur inthe mitochondria. aging process Inare our energy Cert that is brain specific, but highly expressed in acute leukemia- mutantmetabolism: mouse Caloric model, restriction, ceramide insulin accumulation pathways in ER and results electron in -BAALC (brain and acute leukemia, cytoplasmic) [1]. Our mild ER adaption response to the stress, but severe mitochondria study confirmed the activity of N-terminal myristoylation and dysfunction. With the altered sphingolipids components in palmitoylation of BAALC 1-6-8 through mutation study. Emerging plasma membrane and organelles, developmental defects markerevidence to suggest prognosis that BAALC outcome expression of a sub-group stops differentiation acute myeloid of of heart in this Cert mutant mouse lead embryo to die from myeloid [2]. Clinical data underlined that BAALC is a suitable hypothesize that the biological aging process in cells due to knockoutleukemia mouse [3]. However, seems do the not detailed survive, mechanism our future ofstudy BAALC will dysfunctionheart failure. of As mitochondria the primary is researcher the major causeof the of mouse organogenetic model, I employ1-6-8 in knock-in hematopoietic or transgenic system animal remains models, unclear. and utilize The BAALC other failure in Cert null mice. Our next study will explore how lipid metabolism play a role in aging process with Cert mutant mouse and maintenance of stemness in oncology (hematology), uncover model, we will develop and discover some compounds involved platforms to decipher the mechanism of BAALC in introduction in lipid metabolism that may able to rescue the developmental pattern of its diverse isoforms in leukemia patients, explore the defect of cardiovascular that have high morbidity in new births. the regulation rules of expression of BAALC and expression

rafts; discover stem cell-related therapeutic approaches for very important components in functional microdomains of cancer, chronic infectious diseases, cardiovascular diseases, membraneGlycolipids in mammals. and glycoprotein’s Especially, in (glycosylated Immune system, proteins) all kinds are of immunoglobulins are glycoproteins. It is reported that Cert provideosteoporosis, reliable Alzheimer’s data for the disease improvement and other of human aging health. associated an aggressive cancer type in metastasis [7]. Consistent with diseases. Our scientific designing, and ethical clinical trials will expression decreases in Triple Negative Breast Cancer (TNBC), References

the recent discovery [8]: Lipid rafts and its associated actin 1. Wang X, Tian QB, Okano A, Sakagami H, Moon IS, Kondo H, et al. cytoskeleton contribute to the localization and function of ABC N-terminal myristoylation and palmitoylation, and interacts with a, BAALC 1-6-8 protein is targeted to postsynaptic lipid rafts by its transporter, the marker of side population in flow cytometry, our stemunpublished cell, hormone data with and headgrowth and factor neck enhance Squamous hypoxic cell carcinoma response but not b, subunit of Ca2+/calmodulin-dependent protein kinase II. J (HNSCC) suggest that hypoxia induces the characteristic of cancer 2. Neurochem. 2005; 92(3): 647-659. Heuser M, Berg T, Kuchenbauer F, Lai CK, Park G, Fung S, et al. isof alsoHNSCC, the which precursor are probably for biosynthesis the reason of glucosylceramide, of resistance to Functional role of BAALC in leukemogenesis. Leukemia. 2012; 26(3): whichchemotherapy reduce the for sensitivitycancers. Besides of cancer the cellssphingomyelin, to drugs and ceramide involve 3. 532-536. doi: 10.1038/leu.2011.228. in maintaining features of cancer stem cell. In our Cert mutant andWeber detection S, Alpermann of residual T, Dicker disease F, Jeromin in cytogenetically S, Nadarajah N, normal Eder C, acuteet al. mouse model, the glucosylceramide is probably overproduced by BAALC expression: a suitable marker for prognostic risk stratification ceramide accumulation. In addition, our unpublished data shows that the expression level of Tenascin C (TNC), a glycoprotein myeloid leukemia. Blood Cancer J. 2014; 4: e173. doi: 10.1038/ 4. bcj.2013.71. normally found abundant in extracellular matrix, associate with Changqing Yuan, Raghavendra Pralhada Rao, Nahid Jesmin, Takeshi work, our company will study the mechanism of chemotherapy Bamba, Kunio Nagashima, Alberto Pascual, et al. CDase is a pan- resistanthypoxia ininvolved aggressive by lipid HNSCC metabolism cell lines. with With Cert thesemutant previous mouse, Ceramidase in Drosophila. Mol Biol Cell. 2011; 22(1): 33-43. doi: 10.1091/mbc.E10-05-0453. and develop drugs to neutralize the toleration to anti-cancer of Zhang HL, et al. Mitochondrial degeneration and not apoptosis is the Glycolipids. 5. primaryWang X, cause Rao RP, of embryonicKosakowska-Cholody lethality in T, ceramide Masood transfer MA, Southon protein E, In infectious diseases, both bacteria and virus alter the lipid mutant mice. J Cell Biol. 2009; 184(1): 143-158. doi: 10.1083/ jcb.200807176. metabolism during the replication and secretion. Secretion Ceramide transfer protein function is essential for normal oxidative 6. Rao RP, Yuan C, Allegood JC, Rawat SS, Edwards MB, Wang X, et al. of cytokines in inflammation and production of antibodies to betweenspecific stimulation ligands and of antigens receptors, need internalization rearrangement of of membrane lipid rafts, stress response and lifespan. Proc Natl Acad Sci USA. 2007; 104(27): 7. forprogression signaling of transduction endocytosis and need exocytosis. particular For functional the interaction lipid 11364-11369. Heering J, Weis N, Holeiter M, Neugart F, Staebler A, Fehm TN, et al. Loss of the ceramide transfer protein augments EGF receptor withrafts virus clusters. in serum For example,to moderate in chronicimmune Hepatitis response Cfrom virus the (HCV) host, signaling in breast cancer. Cancer Res. 2012; 72(11): 2855-2866. doi: lipoproteinsinfection, lipoproteins also regulate and the membrane entry of glycoprotein’s virus into hepatocytes. combined 10.1158/0008-5472.CAN-11-3069. The disorder of lipid metabolism causes the liver cirrhosis, even 8. Kok JW, Klappe K, Hummel I. The Role of the Actin Cytoskeleton and Hepatocellular carcinoma [9]. Our recent study established an Lipid Rafts in the Localization and Function of the ABCC1 Transporter. 9. angiogenic animal model through intervention and induction of Advances in Biology. 2014; 105898. M, Diago M, et al. Hepatitis C virus infection alters lipid metabolism Rojas A, del Campo JA, Maraver M, Aparcero R, Garcia-Valdecasas

seekperiodontitis stem cell [10]. therapy We will in study treatment the mechanism of cardiovascular, of vasculature bone depending on IL28B polymorphism and viral genotype and modulates resorptionalong with andbone bone resorption metastasis in inflammatory of cancer. microenvironment, gene expression in vivo and in vitro. Journal of Viral Hepatitis. 2014; 21(1): 19-24. doi: 10.1111/jvh.12209. Taken together, our company will conduct innovative 10. Zhang ZY, Ge XJ, Zheng WX, Chen RZ, Wang X. VEGFA And IL17 research on targeting lipid functional microdomains, lipid Expression Reveals Their Potential Functional Crosstalk in Periodontitis Rats-A New Animal Model for Angiogenesis Study. Journal of Microbiology & Experimentation. 2014; 1(4).

Citation: : 2 of 2

Wang X (2015) Targeting Lipid Rafts, Seeking Cures for Diseases. SOJ Microbiol Infect Dis 3(1) 1-2. Page