Multiple Sclerosis Archives - Sanford Burnham Prebys

Anne’s experience in stem cell biology began in 2005 when she joined ViaCyte, Inc. where she served as Director of Stem Cell Research and managed an interdisciplinary group working to develop human embryonic stem cells as a replenishable source of pancreatic cells for the treatment of diabetes. Her efforts focused on optimization of the differentiation process, and then on advancing the cell therapy product into development, scaled manufacturing, product characterization, and safety assessment. Anne is a co-inventor on multiple ViaCyte patents, and her team’s contributions played a key role in securing a $20 MM California Institute of Regenerative Medicine (CIRM) Award.

In June of 2010, Sanford Burnham Prebys recruited Anne as Director of Cell Biology to lead efforts in stem cell-based disease modeling at the Conrad Prebys Center for Chemical Genomics. Her role includes leading internal research projects, as well as external collaborations with academic and industry partners. Anne’s research program is primarily focused on neurological and neuromuscular disease, with the aim of designing human cell-based models and assays that recapitulate disease phenotypes, yet have the throughput and reproducibility required for drug discovery. Towards this goal her group has worked to develop a suite of foundational high throughput assays to monitor neuronal morphology, mitochondrial function, and electrophysiology, using high content screening, and multi-electrode array formats. They have conducted high-throughput drug screens on muscular dystrophy patient cells, hiPSC-derived cardiomyocytes, and hiPSC-derived neurons, including from Alzheimer’s patient specific hiPSC. Anne is a principal investigator for the National Institute of Mental Health (NIMH) National Cooperative Reprogrammed Cell Research Groups consortium and has also received research support from rare disease foundations and pharma sponsored collaborations. She also serves on advisory boards for multiple biotechnology companies.

Related Disease
Aging-Related Diseases, Alzheimer’s Disease, Amyotrophic Lateral Sclerosis (Lou Gehrig’s Disease), Congenital Disorders of Glycosylation, Glycosylation-Related Disorders, Multiple Sclerosis, Muscular Dystrophy, Neurodegenerative and Neuromuscular Diseases

Phenomena or Processes
Cell Biology, Development and Differentiation, Development of Neuronal Circuits, Embryonic/Pluripotent Stem Cells, Neurobiology, Neurodegeneration, Neurogenesis, Neuron-Glia Interactions in Myelin, Neurotransmitters, Synapse Formation and Maturation, Synapse Function, Synaptic Transmission

Research Models
Human Adult/Somatic Stem Cells, Human Cell Lines, Human Embryonic Stem Cells

Techniques and Technologies
Cellular and Molecular Imaging, Drug Discovery, Electrophysiology, Fluorescence Microscopy, High Content Imaging, In vivo Modeling, Microarrays, Molecular Genetics

Dr. Anne Bang is an experienced cell biologist and stem cell expert who leads efforts at the Prebys Center to develop patient cell specific and human induced pluripotent stem cell (hiPSC)-based disease models for drug screening and target identification. Her research program is primarily focused on neurological and neuromuscular disease, with the aim of designing human cell based models and assays that reflect higher order cellular functions and recapitulate disease phenotypes, yet have the throughput and reproducibility required for drug discovery. Towards this goal her group has worked to develop a suite of foundational high throughput assays to monitor neuronal morphology, mitochondrial function, and electrophysiology, using high content screening, and multi-electrode array formats. They have conducted high-throughput drug screens on muscular dystrophy patient cells, hiPSC-derived cardiomyocytes, and hiPSC-derived neurons, including from Alzheimer’s patient specific hiPSC. Anne is a principal investigator for the National Institute of Mental Health (NIMH) National Cooperative Reprogrammed Cell Research Groups consortium, and also receives research support from rare disease foundations and pharma sponsored collaborations.

Anne Bang’s Research Report

Publications

High content screen for compounds that modulate neurite outgrowth and retraction of human induced pluripotent stem cell derived neurons. Sherman, S.P. and A.G. Bang. Dis Model Mech. 2018 Feb 2;11(2):dmm031906.
AAV-Mediated Mini-Agrin Delivery is Unable to Rescue Disease Phenotype in a Mouse Model of Limb Girdle Muscular Dystrophy Type 2I. Vannoy, C.H., H. Zhou, C. Qiao, X. Xiao, A.G. Bang*, Qi L. Lu* Am J Pathol. 2017 Feb;187(2):431-440. (*corresponding authors).
Neuronal medium supporting physiological synaptic activity and fundamental functions of human neurons in vitro. Bardy C., M. Van Den Hurk, C. March and, T. Eames, R. Hernandez, M. Kellogg, M. Gorris, B. Galet, V. Palomares, J. Brown, A.G. Bang, J. Mertens, L. Boehnke, L. Boyer, S. Simon, F. H. Gage. Proc Natl Acad Sci U S A. 2015 May 19;112(20):E2725-34.
A Scalable System for Production of Functional Pancreatic Progenitors from Human Embryonic Stem Cells. Schulz T., H.Y. Young, A.D. Agulnick, J. Babin, E.E. Baetge, A.G. Bang, A. Bhoumik, et al. PLoS One. 2012;7(5):e37004.
Novel surface markers for the isolation and transplantation of pancreatic cells derived from human embryonic stem cells. Kelly O.G., M.Y. Chan, L.A. Martinson, K. Kadoya, T. Ostertag, K. Ross, M. Richardson, M.K. Carpenter, K.A. D’Amour, E. Kroon, M. Moorman, E.E. Baetge, and A.G. Bang. Nat Biotechnol. 2011 Jul 31;29(8):750-6.
Characteristics and characterization of human pluripotential stem cells. Bang A.G. and M.K. Carpenter. In Essentials of Stem Cell Biology, 2009 Nov 30;(38)339-343
Deconstructing pluripotency. Bang A.G. and M.K. Carpenter. Science 2008 Apr 4;320(5872):58-9.
Pancreatic endoderm derived from human embryonic stem cells generates glucose responsive insulin-secreting cells in vivo. Kroon E., L. A. Martinson, K. Kadoya, A.G. Bang, O.G. Kelly, S. Eliazer, H. Young, M. Richardson, N.G. Smart, J. Cunningham, A.D. Agulnick, D’Amour KA, M.K. Carpenter & E.E. Baetge. Nat Biotechnol. 2008 Apr;26(4):443-52.
Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. D’Amour K.A,. A.G. Bang, S. Eliazer, O.G. Kelly, A.D. Agulnick, N.G. Smart, M.A. Moorman, E. Kroon, M.K. Carpenter & E.E. Baetge. Nat Biotechnol. 2006 Nov;24(11):1392-401

Patents

Jackson, M., and Bang, A.G. 2013. Theranostics platform and methods of use, Patent Application No. PCT/US13/26448, Sanford Burnham Medical Research Institute, La Jolla, CA.
Kelly, O.G., and Bang, A.G. 2012. Methods for purifying endoderm and pancreatic endoderm cells from human embryonic stem cells, United States Patent 8,338,170, ViaCyte, Inc., San Diego, CA.
D’Amour K., Bang A., Baetge, E. 2012. Endocrine precursor cells, pancreatic hormone-expressing cells and methods of production. United States Patent 8,129,182, ViaCyte, Inc., San Diego, CA.
Green, C., Yu X., Bang A., Brandon, E., Kelly, O., Agulnick, A., Baetge, E., D’Amour K., Schulz, T., Robins, A. 2011. Stem cell aggregate suspension compositions and methods of differentiation thereof. United States Patent 8,008,075, ViaCyte, Inc., San Diego, CA.

Oct 11, 2024
Anne Bang joins $12.7M research project on the genetic basis of autism and schizophrenia
Sanford Burnham Prebys scientist and an international team are funded by the California Institute for Regenerative Medicine.
Oct 11, 2024
Aug 18, 2022
Using stem cells to study the biochemistry of learning
A method for studying human neurons could help researchers develop approaches for treating Alzheimer’s, schizophrenia and other neurological diseases.
Aug 18, 2022
Dec 8, 2020
What scientists are learning about COVID-19 and the brain
We caught up with cell biologist Anne Bang, who recently teamed up with her husband to study how SARS-CoV-2 affects…
Dec 8, 2020
Feb 7, 2019
Drug screen conducted at Sanford Burnham Prebys identifies new therapeutic avenues for Alzheimer’s disease
A screen of more than 1,600 Food and Drug Administration (FDA)–approved drugs performed at SBP’s Conrad Prebys Center for Chemical
Feb 7, 2019

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Showing 3 of 3

High-throughput screen for compounds that modulate neurite growth of human induced pluripotent stem cell-derived neurons.

Sherman SP, Bang AG

Dis Model Mech 2018 Feb 2 ;11(2):

Cell-surface markers for the isolation of pancreatic cell types derived from human embryonic stem cells.

Kelly OG, Chan MY, Martinson LA, Kadoya K, Ostertag TM, Ross KG, Richardson M, Carpenter MK, D’Amour KA, Kroon E, Moorman M, Baetge EE, Bang AG

Nat Biotechnol 2011 Jul 31 ;29(8):750-6

Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

Bardy C, van den Hurk M, Eames T, Marchand C, Hernandez RV, Kellogg M, Gorris M, Galet B, Palomares V, Brown J, Bang AG, Mertens J, Böhnke L, Boyer L, Simon S, Gage FH

Proc Natl Acad Sci U S A 2015 May 19 ;112(20):E2725-34

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Alexander Strongin earned his PhD from Moscow State University in Russia in 1972 and his D.Sci. degree from the Institute of Microbial Genetics in Moscow in 1983. From 1982 to 1988, Dr. Strongin was head of the Laboratory of Functional Enzymology at the Institute of Genetics of Microorganisms in Moscow. He served as head of the Department of Biotechnology and Laboratory of Protein Engineering, Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, from 1988 to 1990. From 1990 to 1994, he was a visiting professor of biochemistry in the Division of Dermatology at Washington University School of Medicine, St. Louis, Missouri. Dr. Strongin has worked in the La Jolla area since 1994, as senior staff scientist in the Biology Division at General Atomics, 1994-1995, and as senior staff scientist at the La Jolla Institute for Experimental Medicine, 1995-1999. Dr. Strongin joined Sanford Burnham Prebys on September 1, 1999.

Related Disease
Anthrax, Arthritis, Brain Cancer, Breast Cancer, Cancer, Hepatitis C, Multiple Sclerosis, Prostate Cancer, Type 1 Diabetes

Tumors produce unique enzymes, which by degrading the normal tissue provide an opportunity for tumor to grow in size and metastasize. These enzymes are called matrix metalloproteinases or MMPs. MMPs are a primary target for the design of anti-cancer pharmaceuticals. Our work aims to lay the foundation from which efficient therapeutics could ultimately be derived. Dr Strongin’s research is focused on the fundamental mechanisms involving MMPs in the processes of cell migration, cell proliferation and metastasis. The far-reaching goals of this pioneering research are to gain an understanding of how MMPs by cleaving the surrounding tissue and by affecting cell surface receptors govern locomotion of malignant cells. This knowledge is critical for design of efficient pharmaceuticals that may find applications in a variety of disease conditions including cancer, arthritis and stroke.

Alex Strongin’s Research Report

Degradation of the extracellular matrix and tissue remodeling play critical roles in tumor progression, particularly in invasion, metastasis, and neovascularization. Matrix metalloproteinases (MMPs) are essential for matrix proteolysis. Understanding the roles of MMPs in tumor growth and angiogenesis is of paramount importance to novel strategies for treatment of malignant tumors. Our primary goal is to characterize mechanisms of MMP activation involved in spatial and temporal control of focal proteolysis and to increase knowledge of cell-mediated matrix remodeling. Recently, we showed that heteromolecular assemblies involving MMPs and integrins that can simultaneously activate and dock MMPs are present on the surfaces of tumor cells. Apparently, these mechanisms of MMP activation are instrumental in clustering activated proteinases and integrins at the protrusions at the invasive front of migrating cells and at the invasive front of tumors (see Figure).

Interactions between MMPs and integrins, critical to spatial and temporal control of proteolysis, most likely are common for many cell types. To test our hypotheses and to outline novel approaches to control the activity of MMPs, we are examining mechanisms involved in activation, docking, and cross talk of MMPs and integrins in vivo and in vitro. We expect to experimentally show at the cell and protein sequence levels how the temporal and spatial regulation of matrix degradation is linked to dynamic changes of cell shape and cytoskeleton and to identify molecular mechanisms of cell motility. The immediate results of these studies will be improved diagnosis and treatment of malignant neoplasms.

Schematic depiction of the MMP-integrin molecular assembly. Inhibitory effects of tissue inhibitors of metalloproteinases (TIMPs) and the C-terminal domain of MMP-2 are shown by black arrows. The conversions of MMP-2 are shown by open arrows. The question mark stands for a cytoskeletal protein involved in a complex with membrane type-1 matrix metalloproteinase (MT1-MMP). This assembly is critical for docking, activation, and cross talk of MMPs and integrins and is intimately involved in regulating focalized matrix degradation and cell locomotion. MT1-MMP is in immediate proximity to integrin alpha vbeta 3. Both MT1-MMP and the integrin associate with the cytoskeleton. TIMP-2 links MT1-MMP (“a receptor”) and the secretory MMP-2 proenzyme. The second molecule of MT1-MMP (“an activator” that is free of TIMP-2) activates integrin alpha vbeta 3 by limited proteolysis of the beta 3 integrin subunit. The activator initiates the activation of pro-MMP-2 by cleaving the N-terminal part of the 68-kDa MMP-2 latent zymogen. The 64-kDa activation intermediate of MMP-2 efficiently associates with activated integrin alpha vbeta 3 via the C-terminal domain of the enzyme. The 64-kDa to 62-kDa autocatalytic maturation occurs if MMP-2 is complexed with the integrin. The mature MMP-2 enzyme transiently associated with the integrin at the surface of tumor cells accelerates the directional invasion of the cells. Additionally, if transiently complexed with the integrin at the surface of host stromal cells, the enzyme facilitates tumor neovascularization. TIMPs, including TIMP-2 and TIMP-1, efficiently inhibit the activity of soluble MMP-2. By providing links between integrins, MMPs, and TIMPs and, more generally, between cell shape and focal proteolysis, this model represents basic mechanisms of pro-MMP-2 activation and illustrates a coordinated interplay of inhibitors, proteinases, and integrin adhesion receptors at cell surfaces.

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Showing 1 of 1

The acidic sequence of the NS4A cofactor regulates ATP hydrolysis by the HCV NS3 helicase.

Shiryaev SA, Chernov AV, Shiryaeva TN, Aleshin AE, Strongin AY

Arch Virol 2011 Feb ;156(2):313-8

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William Stallcup earned his PhD in biochemistry from the University of California at Berkeley in 1972. He did postdoctoral work at the Salk Institute, where he was appointed Assistant Professor in 1976. Dr. Stallcup was recruited to Sanford Burnham Prebys in 1984.

Related Disease
Atherosclerosis, Brain Cancer, Breast Cancer, Multiple Sclerosis, Obesity, Skin Cancer and Melanoma

Molecules that control cell proliferation and motility are very important for both normal development and the pathology of many diseases. During development, immature precursor cells must undergo an extensive program of cell division in order to generate the millions of cells required to form a mature organism. In many cases these cells must also be able to migrate long distances to reach their final resting spots in the body. In diseases such as cancer, the mechanisms regulating both cell proliferation and migration are disturbed so that cells divide and migrate in an uncontrolled manner. Dr. Stallcup’s laboratory studies a cell surface protein called NG2 that appears to be involved in both cell proliferation and motility. During normal development, NG2 is found on immature cells that are actively dividing and migrating in tissues such as the brain and vasculature. When cells in these tissues mature, they no longer produce NG2. However, when cells become injured or cancerous, they once again produce NG2 and re-acquire the ability to divide and migrate. Work in the Stallcup lab is aimed at understanding the regulation of NG2 so that cell proliferation and motility can be controlled in pathological situations.

William Stallcup’s Research Report

Cell Surface Molecules in the Developing Nervous System

The NG2 chondroitin sulfate proteoglycan is a membrane-spanning protein expressed by several types of immature progenitor cells, including oligodendrocyte progenitors, chondroblasts, skeletal muscle myoblasts, smooth muscle cells, and pericytes. NG2 is also expressed by several types of highly malignant neoplasms, including melanomas, glioblastomas, and lymphomas (Burg et al, 1998). Both the progenitor cells and the tumor cells are mitotic and in some cases highly motile. There is evidence to suggest that NG2 plays a role in both growth control and motility during the development of these cell types. We are currently investigating systems in which NG2 appears to be involved in the signaling mechanisms that control these processes. We have identified three classes of signal transduction mechanisms that may be mediated or modulated by NG2.

NG2 is required for optimal activation of the PDGF alpha receptor by PDGF-AA. NG2-positive smooth muscle cells migrate and proliferate well in response to both PDGF-AA and PDGF-BB, while NG2-negative smooth muscle cells (derived from NG2 knockout mice) respond only to PDGF-BB (Grako et al, 1999). Since we can show that the alpha receptor does not undergo autophosphorylation in response to PDGF-AA, we believe the defect in the NG2-negative cells must lie at the level of receptor activation. We have now demonstrated that NG2 is capable of binding PDGF-AA (but not PDGF-BB) with fairly high affinity, and thus may participate in sequestering the growth factor or in presenting it to the signaling receptor (Goretzki et al, 1999). In this case, therefore, we believe that NG2 plays an auxilliary role to the actual signal transducing molecule.

NG2-positive smooth muscle cells and several NG2-positive cell lines also proliferate and migrate well in response to soluble type VI collagen, an extracellular matrix ligand for the proteoglycan. In contrast, the NG2-negative counterparts of these cells respond much less effectively. We have preliminary indications that the response to soluble type VI collagen involves activation of the MAP kinases Erk-1 and 2, similar to what is seen during stimulation with growth factors. Further experiments will be required to elucidate the details of this signaling cascade and to determine whether NG2 is involved directly or indirectly in activating this pathway.

The third signaling mechanism is observed upon engagement of NG2 by the substratum, a process that results in cell spreading and migration. Importantly, spreading and migration do not occur with cells expressing NG2 variants lacking the cytoplasmic domain of the proteoglycan, suggesting that interaction of NG2 with cytoplasmic ligands is required for these processes to take place. Analysis of the cytoskeletal rearrangements taking place in spreading cells reveals the extension of both filopodia and lamellipodia in response to NG2 engagement (Figure 1). These two processes are thought to be controlled by activation of the rho family GTPases cdc42 and rac, respectively, suggesting that NG2 engagement triggers activation of these GTPases. We are currently investigating the details of the signaling cascades involved in these phenomena, as well as attempting to identify cytoplasmic binding partners for NG2 which may serve as effector molecules for activation of downstream signaling events.

Organization of Actin in Spreading U251 Transfectants

Wild type NG2 transfectants were allowed to spread for 20 (a-d) or 60 (e-f) minutes on surfaces coated with PLL, mAb D120, mAb N143, or mAb beta(1). Cells were then fixed with two percent paraformaldehyde and stained with rhodamine phalloidin to allow visualization of filamentous actin. Radial actin spikes characteristic of filopodia were seen on PLL and mAb D120, while cortical actin bundles characteristic of membrane ruffles were seen on mAb N143 and mAb beta(1). After 60 minutes, stress fibers were apparent in all cases.

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Showing 2 of 2

Differential phosphorylation of NG2 proteoglycan by ERK and PKCalpha helps balance cell proliferation and migration.

Makagiansar IT, Williams S, Mustelin T, Stallcup WB

J Cell Biol 2007 Jul 2 ;178(1):155-65

An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis.

Virgintino D, Girolamo F, Errede M, Capobianco C, Robertson D, Stallcup WB, Perris R, Roncali L

Angiogenesis 2007 ;10(1):35-45

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Barbara Ranscht earned her PhD in Cell Biology/Developmental Neurobiology from the University of Tübingen, Germany in 1981. Her postdoctoral training was at King’s College in London, U.K., and the Massachusetts Institute of Technology in Cambridge, Massachusetts. Dr. Ranscht joined Sanford Burnham Prebys in 1987, and holds an adjunct professorship in the Department of Neurosciences at University of California, San Diego. From 1989 to 1992, Dr. Ranscht was the recipient of a McKnight Scholarship.

Education

1981: PhD, University of Tübingen, Germany Neurobiology

Related Disease
Attention-deficit hyperactivity disorder (ADHD), Cancer, Cardiovascular Diseases, Metabolic Syndrome, Multiple Sclerosis, Neurological and Psychiatric Disorders

Our lab studies cell surface interactions that regulate signaling networks in the nervous and cardiovascular systems and in cancer. With focus on the brain, we investigate membrane glycoproteins that enable crosstalk of neurons with the environment during circuitry development and disease. Our group has contributed seminal insights into the functions of Contactin-1 (Cntn1) and T-cadherin (Cdh13) in axon guidance, synapse formation and myelination using knock-out mouse models as well as biochemical, electrophysiological, histological and cellular approaches. Our current work explores the role of T-cadherin in brain circuitries enabling learning and memory formation, and determines how Contactin-1 functions in processes of myelination and remyelination. Exploiting our mouse genetic model, we uncovered a novel function for T-cadherin in protecting against stress-induced cardiac injury, and revealed disruptions of T-cadherin-mediated cellular interactions in cancer. In these latter contexts, our research identified T-cadherin as a major receptor for Adiponectin (Adipoq), a fat-secreted, circulating hormone that is of high clinical interest for its role in positively regulating energy balance and protecting against cellular insult. Current work in the lab aims to understand the molecular processes and signaling pathways regulated by T-cadherin or Contactin-1 in nervous system, cardiovascular and cancer functions with the goal to derive translational applications.

Barbara Ranscht’s Research Report

Functions of T-cadherin/Cdh13 in Neuronal Circuits Involved in Learning and Memory

Cell adhesion molecules play seminal roles in synapse formation, stability and function in the central nervous system (CNS). T-cadherin (Cadherin-13; Cdh13), a glycosylphosphatidylinositol-linked cadherin-type cell adhesion molecule discovered in our laboratory, is prominent in diverse structures of the CNS. Mutations in the human CDH13 gene are linked to neuropsychiatric disorders, most prominently Attention Deficit Hyperactivity Disorders and its comorbidities. Our lab generated mice deficient for T-cadherin gene expression (Tcad-KO) mice to uncover the T-cadherin-dependent neuronal circuitries and probe its contribution to cognitive function. Tcad-KO mice show no overt developmental, neurological or sensory deficiencies, and are indistinguishable from wild type littermates under normal housing conditions. However, challenging the mice in behavioral tests revealed defects in performing select learning tasks. Investigating hippocampal circuitry as a central relay station for learning and memory, we identified reductions in CA1 synaptic transmission and long-term potentiation along with reduced spine densities and maturation of hippocampal pyramidal neurons. Current work aims to link T-cadherin to specific synaptic circuitry, and probe its function through conditional T-cadherin ablation in select neuron populations of the interconnected circuitry to contribute principal understanding to human cognitive disorders.

**Figure 1: T-cadherin expression in adult hippocampus.** T-cadherin staining delineates the dendritic layer of pyramidal neurons in CA1-CA3 subfields, and the molecular layer in the dentate gyrus. Staining is absent from the hippocampus of Tcad-KO mice. NeuN outlines the positions of pyramidal and granule neurons for orientation. *Images by Hedie Badieh-Madhavi, PhD and Jinsha Liu, graduate student.*

Mechanisms of Myelination and Remyelination

Myelin, a multilayered membrane sheath formed by oligodendrocytes around axons in the central nervous system (CNS) enables rapid nerve impulse conduction and sustains neuronal health and survival. Our lab is interested in the signals exchanged between axons oligodendrocytes during myelin formation and repair. Contactin-1, a GPI-linked cell surface glycoprotein, studied in our lab has emerged as one of the critical proteins to regulate axon-glia communication. In peripheral myelinated nerves, Contactin is solely expressed by neurons, and together with Caspr clusters at the paranodal axon domain to orchestrate formation of the septate-like axoglial junctions. In the CNS, Contactin delineates paranodes and nodes of Ranvier in mature myelin, and oligodendrocytes during the process of active myelination. We recently documented a vital dual role of Contactin-1 in central myelin formation: Contactin-mediated interactions between axons and oligodendrocytes regulate the extension and wrapping of myelin membranes, and loss of these interactions leads to hypomyelination in the mouse knockout model. The residual myelin is non-functional due to disrupted paranodal junctions that are characterized by loss of Contactin-associated paranodal Caspr, mislocalized potassium channels and disrupted transverse bands. Current work in the lab investigates the distinct contributions of Contactin in neurons and oligodendrocytes in mice with conditional Contactin-1 deletion, myelinating co-cultures and mouse models of myelin injury. If indicated, this work will form the basis for translational aspects of myelin repair.

**Figure 2:** In mouse P10 optic nerve, Ccntactin (green) delineates oligodendrocyte progenitor cells demarcated by NG2 (red). Staining for Contactin does not overlap with APC (blue), a marker for mature oligodendrocytes. *Image by Gulsen Colakoglu, PhD*

**Figure 3:** In mice deficient for Contactin-1, loss of axon-glia cross-talk leads to hypomyelination. Shown here are electron micropgraphs from P17 wildype and knockout (KO) optic nerves. *Images Erik O. Berglund, MD, PhD*

Adiponectin – T-cadherin/Cdh13 Signaling in Cardioprotection

Adiponectin is of significant clinical interest for its potency in counterbalancing the adverse effects of obesity-linked metabolic disease and cardiovascular dysfunctions. Research in the field is increasingly focusing on local actions of APN in its target tissues where binding to the cell surface leads to activation of intracellular signal transduction pathways that increase cellular energy and counteract adverse processes such as generation of reactive oxygen species, misbalanced cellular metabolism, and apoptotic cell death. Our lab identified T-cadherin as a major ligand-binding receptor for Adiponectin in the cardiovascular system (Denzel et al, 2010). T-cadherin effectively sequesters APN from serum and its absence leads to excessive APN concentrations in the circulation. Under cardiac stress, induced by pressure overload, T-cadherin is necessary to confer cardioprotection through APN. Downstream, APN engagement with T-cadherin activates the AMP-activated protein kinase (AMPK), a major downstream signaling target of APN. Since T-cadherin is a GPI-linked cell surface glycoprotein lacking the cytoplasmic region, it is our working model that T-cadherin connects through associated molecules to intracellular signaling pathways. We are exploring the heptahelical APN-receptors AdipR1/R2 as prime candidates while considering alternative possibilities.

**Figure 4: T-cadherin requirement in reverting exaggerated cardiac hypertrophy in APN-KO mice.** Trichorme-stained hearts (left) show cardiac hypertrophy induced by pressure overload. Hypertrophy can be reverted in Adiponectin knockout (APN KO) mice by adenovirus-mediated expression of recombinant Adiponectin (adAPN; upper panel). In the absence of T-cadherin, APN-KO cardiac tissue does not respond (upper panel). Control virus expressing green fluorescent protein (adGFP) has no effect on the heart hypertrophic phenotype (lower panels). Mechanistically, as shown by immunohistochemistry, low T-cadherin expression in APN-KO hearts (Tcad, green, lower panel) is upreguated by adAPN (Tcad, green, upper panel) and binds adAPN which triggers downstream cardioprotective pathways. *Data by Martin Denzel, PhD*

Combining our cellular and functional analyses of T-cadherin with the extensive expertise in heart function at our Institute, we hope to make headway in determining APN-associated signaling pathways involving T-cadherin and AdipoR receptors. This work will fill the current knowledge gap of understanding APN interactions with its target cells in the cardiovascular system and may aid the development of novel molecular approaches for cardioprotection.

T-cadherin/Cdh13 in Cancer

T-cadherin has also emerged as one of the key molecules altered in diverse types of cancer. Epithelial-mesenchymal transition (EMT) during neoplasia is characterized by the down-regulation of T-cadherin/CDH13, and this silencing is linked to increased proliferative and invasive potential of human cancers. We used the mouse genetic model to investigate functions of T-cadherin in tumors. In the mouse mammary tumor virus-driven polyoma middle T (MMTV-PyV-mT) model, T-cadherin is down-regulated from neoplastic epithelial cells while it is upregulated in the tumor vasculature. Under conditions of T-cadherin deficiency, MMTV-PyV-mT induced tumor growth occurs with delayed onset and at reduced growth rates that result in prolonged animal survival over non-mutant mice. Our analyses identified reduced tumor vascularization as the major underlying mechanism for this beneficial outcome. T-cadherin’s pro-angiogenic role is mediated by the association of Adiponectin: The APN-deficient MMTV-PyV-mT tumor phenotype mirrors the defects in T-cadherin knockout mice, and in vitro silencing of T-cadherin in endothelial cells abrogates the cellular responses to APN. Our lab is now interested in understanding the mechanism by which T-cadherin binding to Adiponectin affects endothelial cell function and develop strategies to control tumor angiogenesis.

**Figure 5: T-cadherin in the neoplastic mammary gland.** A. In early stage MMTV-PyV-mT mouse tumors, T-cadherin (green) and E-cadherin (red) are down-regulated from developing neoplasias (a-c; central white box magnified as insert) while both cadherins are expressed on the non-cancerous ductal epithelium (white arrows in a-c), Histology shows the pathology of a normal duct (asterisk) and developing neoplasias (d, black arrows; scale bars 50 mm). In developed MMTV-PyV-mT tumors, T-cadherin (green in e) is upregulated on the CD31-positive tumor vasculature (f and g). The pathology of a MMTV-PyV-mT tumor is shown in f. B, T-cadherin is detected as a protein doublet of 95 kD and 115kD by Western blotting of normal mouse mammary fat pads and is down-regulated in the neoplastic mammary gland. Beta tubulin Is used as a gel loading control. No T-cadherin protein is detected in the T-cadherin-deficient (KO) MMTV-PyV-mT tumors. *Data by Lionel Hebbard, PhD*

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Showing 2 of 2

Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system.

Çolakoğlu G, Bergstrom-Tyrberg U, Berglund EO, Ranscht B

Proc Natl Acad Sci U S A 2014 Jan 21 ;111(3):E394-403

T-cadherin is essential for adiponectin-mediated revascularization.

Parker-Duffen JL, Nakamura K, Silver M, Kikuchi R, Tigges U, Yoshida S, Denzel MS, Ranscht B, Walsh K

J Biol Chem 2013 Aug 23 ;288(34):24886-97

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Dr. Yu Xin (Will) Wang received his PhD at the University of Ottawa where he identified cellular asymmetry and polarity mechanisms regulating muscle stem cell self-renewal and skeletal muscle regeneration. He then carried out postdoctoral training at Stanford University School of Medicine developing single cell multi-omic approaches to characterize the regenerative process and what goes awry with disease and aging.

“I’ve always had a passion for science and became fascinated with how the body repairs and heals itself when I was introduced to the potential of stem cells in regenerative medicine. I was struck by the ability of a small pool of muscle stem cells that can rebuild and restore the function of muscle. My lab at Sanford Burnham Prebys aims to better understanding the repair process and harness our body’s ability to heal in order to combat chronic diseases and even counteract aging.“

Education and Training

Postdoctoral Fellowship, Stanford University School of Medicine
PhD in Cellular Molecular Medicine, University of Ottawa, Canada
BS in Biomedical Sciences, University of Ottawa, Canada

Prestigious Funding Awards

2020: NINDS K99/R00 Pathway to Independence Award

Honors and Recognition

Governor General’s Gold Medal – Canada

Related Disease
Aging-Related Diseases, Amyotrophic Lateral Sclerosis (Lou Gehrig’s Disease), Arthritis, Cachexia, Inflammatory/Autoimmune Disease, Multiple Sclerosis, Muscular Dystrophy, Myopathy, Neurodegenerative and Neuromuscular Diseases, Sarcopenia/Aging-Related Muscle Atrophy, Spinal Muscular Atrophy

Phenomena or Processes
Adult/Multipotent Stem Cells, Aging, Cell Signaling, Development and Differentiation, Epigenetics, Exercise, Extracellular Matrix, Neurogenesis, Organogenesis, Regenerative Biology, Transcriptional Regulation

Anatomical Systems and Sites
Immune System and Inflammation, Musculoskeletal System, Nervous System

Research Models
Clinical and Transitional Research, Computational Modeling, Human Adult/Somatic Stem Cells, Mouse

Techniques and Technologies
3D Image Analysis, Bioinformatics, Cellular and Molecular Imaging, Gene Knockout (Complete and Conditional), Genomics, High Content Imaging, High-Throughput/Robotic Screening, Live Cell Imaging, Machine Learning, Microscopy and Imaging, Proteomics, Transplantation

The Wang lab is interested in elucidating critical cell-cell interactions that mediate the function of tissue-specific stem cells during regeneration and disease, with a focus on how a coordinated immune response can promote regeneration and how autoimmunity impacts tissue function and hinder repair.

Specifically, the Wang lab aims to identify cellular and molecular crosstalk between muscle, nerve, and immune systems to develop targeted therapies that overcome autoimmune neuromuscular disorders and autoimmune aspects of “inflammaging.”

Yu Xin (Will) Wang’s Research Report

The lab’s research is translationally oriented and utilizes interdisciplinary molecular, genetic, computational (machine learning and neural networks), and bioengineering approaches to view biology and disease from new perspectives. We combine multi-omics sequencing and imaging methods to resolve how different cell types work together after injury to repair tissues and restore function. We use a data-driven approach to identify targetable disease mechanisms and, through collaborations with other researchers and clinicians, develop therapies that promote regeneration. Visit our lab website to learn more.

Aug 20, 2024
Mapping the human body to better treat disease
Scientists are investigating the inner workings of our bodies and the cells within them at an unprecedented level of detail.
Aug 20, 2024
Aug 13, 2024
Dodging AI and other computational biology dangers
Sanford Burnham Prebys scientists say that understanding the potential pitfalls of using artificial intelligence and computational biology techniques in biomedical…
Aug 13, 2024
Oct 11, 2023
Inhibiting an enzyme associated with aging could help damaged nerves regrow and restore strength
New research has demonstrated a way to accelerate recovery from peripheral nerve injury by targeting an enzyme that was thought…
Oct 11, 2023
Jan 26, 2023
Three big questions for cutting-edge biologist Will Wang
Will Wang’s spatial omics approach to studying neuromuscular diseases is unique.
Jan 26, 2023
Nov 23, 2022
Yu Xin (Will) Wang joins Sanford Burnham Prebys to advance regenerative medicine
Molecular biologist Yu Xin (Will) Wang, PhD, has joined Sanford Burnham Prebys as an assistant professor in the Development, Aging,…
Nov 23, 2022

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Showing 1 of 1

Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength.

Palla AR, Ravichandran M, Wang YX, Alexandrova L, Yang AV, Kraft P, Holbrook CA, Schürch CM, Ho ATV, Blau HM

Science 2021 Jan 29 ;371(6528):

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Evan Y. Snyder earned his MD and PhD (in neuroscience) from the University of Pennsylvania in 1980 as a member of NIH’s Medical Scientist Training Program (MSTP). He had also studied psychology and linguistics at the University of Oxford. After moving to Boston in 1980, he completed residencies in pediatrics and neurology as well as a clinical fellowship in Neonatal-Perinatal Medicine at Children’s Hospital-Boston, Harvard Medical School. He also served as Chief Resident in Medicine (1984-1985) and Chief Resident in Neurology (1987) at Children’s Hospital-Boston. In 1989, he became an attending physician in the Department of Pediatrics (Division of Newborn Medicine) and Department of Neurology at Children’s Hospital-Boston, Harvard Medical School. From 1985-1991, concurrent with his clinical activities, he conducted postdoctoral research as a fellow in the Department of Genetics, Harvard Medical School. In 1992, Dr. Snyder was appointed an instructor in neurology (neonatology) at Harvard Medical School and was promoted to assistant professor in 1996. He maintained lab spaces in both Children’s Hospital-Boston and at Harvard Institutes of Medicine/Beth-Israel Deaconess Medical Center. In 2003, Dr. Snyder was recruited to Sanford Burnham Prebys as Professor and Director of the Program in Stem Cell and Regenerative Biology. He then inaugurated the Stem Cell Research Center (serving as its founding director) and initiated the Southern California Stem Cell Consortium. Dr. Snyder is a Fellow of the American Academy of Pediatrics (FAAP). He also received training in Philosophy and Linguistics at Oxford University.

Related Disease
Alzheimer’s Disease, Amyotrophic Lateral Sclerosis (Lou Gehrig’s Disease), Arthritis, Brain Cancer, Brain Injury, Breast Cancer, Cancer, Childhood Diseases, Congenital Disorders of Glycosylation, HIV-Associated Dementia, Huntington’s Disease, Multiple Sclerosis, Muscular Dystrophy, Neurodegenerative and Neuromuscular Diseases, Neurological and Psychiatric Disorders, Parkinson’s Disease, Peripheral Vascular Disease, Skin Cancer and Melanoma, Spinal Cord Injury, Stroke, Traumatic Injury

We believe the study of stem cell biology will provide insights into many areas: developmental biology, homeostasis in the normal adult, and recovery from injury. Indeed, past and current research has already produced data in these areas that would have been difficult or impossible via any other vehicle. We have engaged in a multidisciplinary approach, simultaneously exploring the basic biology of stem cells, their role throughout the lifetime of an individual, as well as their therapeutic potential. Taken together, these bodies of knowledge will glean the greatest benefit for scientists and, most importantly, for patients. All of our research to date has been preformed in animal models with the ultimate goal of bringing them to clinical trials as soon as possible. Stem cells offer an intriguing mix of controversy, discovery, and hope. Politicians are charged with dealing with the controversial facets of stem cells, as we prefer to focus our energy on their potential for discovery and hope.

The Snyder Lab studies stem cell biology, with the goal of understanding normal development, tissue homeostasis, and recovery from injury and disease. A major focus is neural stem cells (NSCs), which can self-renew and differentiate into neurons, astrocytes, and oligodendrocytes. These properties make NSCs ideal for repair of damage due to injury or disease, but they also make them susceptible to transformation into malignant cancers.

Nov 11, 2024
Seven questions for FDA advisor Evan Snyder
Sanford Burnham Prebys physician-scientist advises the FDA on cell-based therapeutics, tissue engineering and gene therapies.
Nov 11, 2024
Jul 23, 2024
Mini lungs make major COVID-19 discoveries possible
Scientists infect miniature lung organoids with the virus responsible for COVID-19, revealing new ways in which the infection spreads and…
Jul 23, 2024
Jan 25, 2022
New CIRM grant to fund research internships for underrepresented high school students
Thanks to a new grant awarded to Sanford Burnham Prebys by the California Institute for Regenerative Medicine (CIRM), 57 California…
Jan 25, 2022
Nov 18, 2021
From child neurology to stem cells: An interview with Evan Snyder
What do Evan Snyder and Sigmund Freud have in common? Both radically changed how we see the human brain. In…
Nov 18, 2021
Jul 26, 2021
Biomarker could help diagnosis schizophrenia at an early age
Research could lead to blood-based diagnostic test Scientists at Sanford Burnham Prebys have discovered how levels of a protein could…
Jul 26, 2021
Feb 22, 2021
Evan Snyder named Fellow of the American Institute for Medical and Biological Engineering
Renowned stem cell researcher recognized by his peers for seminal contributions to regenerative medicine The American Institute for Medical and…
Feb 22, 2021

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Showing 3 of 3

Probing the lithium-response pathway in hiPSCs implicates the phosphoregulatory set-point for a cytoskeletal modulator in bipolar pathogenesis.

Tobe BTD, Crain AM, Winquist AM, Calabrese B, Makihara H, Zhao WN, Lalonde J, Nakamura H, Konopaske G, Sidor M, Pernia CD, Yamashita N, Wada M, Inoue Y, Nakamura F, Sheridan SD, Logan RW, Brandel M, Wu D, Hunsberger J, Dorsett L, Duerr C, Basa RCB, McCarthy MJ, Udeshi ND, Mertins P, Carr SA, Rouleau GA, Mastrangelo L, Li J, Gutierrez GJ, Brill LM, Venizelos N, Chen G, Nye JS, Manji H, Price JH, McClung CA, Akiskal HS, Alda M, Chuang DM, Coyle JT, Liu Y, Teng YD, Ohshima T, Mikoshiba K, Sidman RL, Halpain S, Haggarty SJ, Goshima Y, Snyder EY

Proc Natl Acad Sci U S A 2017 May 30 ;114(22):E4462-E4471

Proof of concept studies exploring the safety and functional activity of human parthenogenetic-derived neural stem cells for the treatment of Parkinson’s disease.

Gonzalez R, Garitaonandia I, Crain A, Poustovoitov M, Abramihina T, Noskov A, Jiang C, Morey R, Laurent LC, Elsworth JD, Snyder EY, Redmond DE Jr, Semechkin R

Cell Transplant 2015 ;24(4):681-90

Neural stem cells implanted into MPTP-treated monkeys increase the size of endogenous tyrosine hydroxylase-positive cells found in the striatum: a return to control measures.

Bjugstad KB, Redmond DE Jr, Teng YD, Elsworth JD, Roth RH, Blanchard BC, Snyder EY, Sladek JR Jr

Cell Transplant 2005 ;14(4):183-92

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“I love doing science, and a chance to do some good for the world. Sanford Burnham Prebys is a great place to pursue science.“

Professor at UC San Diego and TSR
Department Head, Molecular Neuroscience, Merck Research Labs

Education

1988-1991: Postdoctoral Fellow, Whitehead Institute/MIT, laboratories of Drs. Rudolf Jaenisch and David Baltimore, Developmental and Molecular Biology
1988: MD, PhD, Stanford University School of Medicine, Neuroscience
1981: B.A., University of Hawaii at Manoa, English and Biology

Honors and Recognition

2016: Alzheimer’s San Diego Courage and Hope Award
2014: Thomson Reuters World’s Most Influential Scientific Minds list of highly cited researchers
2011: Killam Lecturer, Montreal Neurological Institute
2010: Journal of Lipid Research Lecturer, Keystone Symposium on Bioactive Lipids: Biochemistry and Diseases, Kyoto, Japan
2007: Chancellor’s Award for Excellence in Neuroscience, LSU Medical School
1999-2006: Independent Scientist Award, NIMH
1994-1999: First Award, NIMH
1993-1995: Basil O’Connor Scholar (March of Dimes Birth Defects Foundation), UCSD
1992-1995: Klingenstein Fellow in the Neurosciences, UCSD
1992-1994: Alfred P. Sloan Research Fellow, UCSD
1988-1991: Helen Hay Whitney Fellow, Whitehead Institute for Biomedical Research
1981-1988: Trainee, Medical Scientist Training Program (MSTP), Stanford University School of Medicine

Related Disease
Alzheimer’s Disease, Hydrocephalus, Multiple Sclerosis

Phenomena or Processes
Aneuploidy, Development and Differentiation, Development of Neuronal Circuits, G-Protein Coupled Receptors, Genome, Lipids, LPA, Mosaicism, S1P, Single Cell

Anatomical Systems and Sites
Brain, Nervous System

Genomic Mosaicism in the Brain
Genomic mosaicism (GM) is a surprising phenomenon whereby cells from the same brain actually have distinct genomes (different DNA sequences). We continue to define forms of GM, involved cell types, and GM’s impact on normal brain function and disease. Diseases of particular interest include Alzheimer’s disease, Down syndrome, Parkinson’s, and other neurodegenerative diseases as well as neuropsychiatric disorders and substance abuse.

Lysophospholipid Receptor Signaling
Lysophospholipids, such as lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are small fat molecules that act through G protein-coupled receptors (GPCRs) on the surface of cells. We continue to study fundamental aspects of their signaling properties, and their disease roles in hydrocephalus (water on the brain), neuropsychiatric disorders (schizophrenia, autism), and neurodegenerative disorders (multiple sclerosis, Alzheimer’s disease).

Neuroscience Drug Discovery
From these and other research areas, new therapeutics for diseases of the brain are being pursued, which include identifying new targets, novel biomarkers, and mechanism-of-action studies. This approach successfully aided in the development of the first oral treatment for multiple sclerosis, fingolimod, and related lysophospholipid receptor compounds. Drug discovery efforts include not only small molecules, but also other forms of molecular therapeutics.

Dec 19, 2024
Combining long- and short-read sequencing in single cells reveals new mRNAs in neurodegenerative diseases
Scientists at Sanford Burnham Prebys uncover gene product mRNA alterations and relationships in three common diseases.
Dec 19, 2024
Apr 16, 2024
Common HIV treatments may aid Alzheimer’s disease patients
Scientists at Sanford Burnham Prebys uncover beneficial links between certain HIV drugs and Alzheimer’s disease.
Apr 16, 2024
Apr 9, 2024
Tiny brain bubbles carry complete codes
Scientists at Sanford Burnham Prebys demonstrated that vesicles traveling between cells in the brain carry more complete instructions for altering…
Apr 9, 2024
Dec 8, 2023
Similarity between vitamin B12 loss and multiple sclerosis revealed
Findings identify molecular signaling pathway that could enhance current MS treatments.
Dec 8, 2023
Dec 15, 2022
Running in the family: La Jollan completes 50th consecutive Honolulu Marathon as his kids finish their first
Dr. Jerold Chun marked a major milestone Dec. 11 in his yearly tradition to honor his father — he completed…
Dec 15, 2022
May 13, 2022
Jerold Chun receives a very special Alzheimer’s grant
Jerold Chun, MD, PhD, has been awarded a new grant for $250,000 from the Coins for Alzheimer’s Research Trust (CART)…
May 13, 2022

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Showing 1 of 1

A Functionally Defined In Vivo Astrocyte Population Identified by c-Fos Activation in a Mouse Model of Multiple Sclerosis Modulated by S1P Signaling: Immediate-Early Astrocytes (ieAstrocytes).

Groves A, Kihara Y, Jonnalagadda D, Rivera R, Kennedy G, Mayford M, Chun J

eNeuro 2018 Sep-Oct ;5(5):

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Dr. Blaho began her research career focused on how bioactive lipids contribute to the innate immune response against bacterial infection, characterizing roles for eicosanoids in the generation and resolution of Lyme arthritis pathology. The wild diversity of lipid species led Dr. Blaho to Weill Cornell Medical College in New York City to pursue postdoctoral training in the field of sphingolipids, particularly sphingosine 1-phosphate (S1P), and its receptors. Advancing to Instructor at Weill Cornell and later, Research Assistant Professor at Sanford Burnham Prebys, Dr. Blaho continued her research in lipid chaperones and receptor signaling, with an emphasis on cell-type differential effects on hematopoiesis and immunity in response to cell stressors. In August of 2019, Dr. Blaho joined the faculty at the Institute as an Assistant Professor in the Immunity and Pathogenesis program.

“The immune system has the power to protect us from invading pathogens and cancer or to initiate a ‘self-destruct’ sequence that consumes us with inflammation and autoimmunity. It is fascinating to me that a simple ubiquitous fat molecule like S1P can control the birth and destiny of immune cells.”

Education

2014-2016: Instructor, Weill Cornell Medicine, Pathology and Laboratory Medicine and Neuroscience
2009-2014: Post-doctoral training, Weill Cornell Medicine, Pathology and Laboratory Medicine
2007-2009: Post-doctoral training, University of Missouri, Columbia, Veterinary Pathobiology
2007: PhD, University of Missouri, Columbia, Molecular Microbiology and Immunology – BS

Funding Awards and Collaborative Grants

National Heart, Lung, and Blood Institute R01
American Heart Association Scientist Development Grant
2014-15: Leon Levy Neuroscience Foundation Grant
2015: Foundation LeDucq SphingoNet Young Investigator Grant
2009-12: National Cancer Institute Individual Ruth L. Kirschstein Post-doctoral Fellowship

Honors and Recognition

2017: British Journal of Pharmacology Lecture: FASEB Summer Research Conference on Lysophospholipids and Related Mediators–from bench to clinic.
2014: Leon Levy Foundation Neuroscience Fellow
2010: Keystone Scholarship, Bioactive Lipids: Biochemistry and Diseases
2008: Keystone Scholarship, Eicosanoids and Other Mediators of Chronic Inflammation
2007: Young Investigator Award in Inflammation, Eicosanoid Research Foundation
2004: National Academy of Sciences Christine Mirzayan Policy Fellow, Institute of Medicine Board on Health Sciences Policy

Related Disease
Biochemistry, Immune Disorders, Inflammatory/Autoimmune Disease, Leukemia/Lymphoma, Molecular Biology, Multiple Sclerosis

Phenomena or Processes
Adaptive Immunity, Apoptosis and Cell Death, Cell Signaling, G-Protein Coupled Receptors, Hematopoiesis, Inflammation, Innate Immunity

Anatomical Systems and Sites
Hematopoietic System, Immune System and Inflammation, Vasculature

Research Models
Human Adult/Somatic Stem Cells, Mouse, Mouse Somatic Stem Cells, Primary Cells

Techniques and Technologies
Cell Biology, Cellular and Molecular Imaging, Confocal Microscopy, Fluorescence Microscopy, Gene Expression, Lipid Bilayers, Mass Spectrometry

The lipid sphingosine 1 phosphate (S1P) is found in high levels in the blood and lymph and is primarily carried by the protein ApoM, found on HDL. S1P can affect the cardiovascular, nervous, and immune systems via interaction with cell surface-expressed receptors, S1P1-5. My work is determining how changing S1P carrier or receptor expression and signaling can affect cells of the immune system, particularly in the bone marrow, and how this alters their ability to respond to stress or infection.

Dec 22, 2021
A strange research ecosystem: Discussing Lyme disease with Victoria Blaho
As an infectious disease immunologist studying Lyme disease, Victoria Blaho is one of a rare breed. Sanford Burnham Prebys assistant…
Dec 22, 2021
Apr 22, 2021
Victoria Blaho receives prestigious Lina M. Obeid Award
The award honors Obeid, a pioneer in the field of sphingolipids and a fierce advocate for women in science. Victoria…
Apr 22, 2021

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Showing 2 of 2

HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation.

Blaho VA, Galvani S, Engelbrecht E, Liu C, Swendeman SL, Kono M, Proia RL, Steinman L, Han MH, Hla T

Nature 2015 Jul 16 ;523(7560):342-6

HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation.

Galvani S, Sanson M, Blaho VA, Swendeman SL, Obinata H, Conger H, Dahlbäck B, Kono M, Proia RL, Smith JD, Hla T

Sci Signal 2015 Aug 11 ;8(389):ra79

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Biography

Research

Recent Bang Lab News

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High-throughput screen for compounds that modulate neurite growth of human induced pluripotent stem cell-derived neurons.

Cell-surface markers for the isolation of pancreatic cell types derived from human embryonic stem cells.

Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

Biography

Research

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The acidic sequence of the NS4A cofactor regulates ATP hydrolysis by the HCV NS3 helicase.

Biography

Research

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Differential phosphorylation of NG2 proteoglycan by ERK and PKCalpha helps balance cell proliferation and migration.

An intimate interplay between precocious, migrating pericytes and endothelial cells governs human fetal brain angiogenesis.

Biography

Education

Research

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Contactin-1 regulates myelination and nodal/paranodal domain organization in the central nervous system.

T-cadherin is essential for adiponectin-mediated revascularization.

Biography

Research

Recent Wang Lab News

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Inhibition of prostaglandin-degrading enzyme 15-PGDH rejuvenates aged muscle mass and strength.

Biography

Research

Recent Snyder Lab News

Select Publications

Probing the lithium-response pathway in hiPSCs implicates the phosphoregulatory set-point for a cytoskeletal modulator in bipolar pathogenesis.

Proof of concept studies exploring the safety and functional activity of human parthenogenetic-derived neural stem cells for the treatment of Parkinson’s disease.

Neural stem cells implanted into MPTP-treated monkeys increase the size of endogenous tyrosine hydroxylase-positive cells found in the striatum: a return to control measures.

Biography

Research

Recent Chun Lab News

Select Publications

A Functionally Defined In Vivo Astrocyte Population Identified by c-Fos Activation in a Mouse Model of Multiple Sclerosis Modulated by S1P Signaling: Immediate-Early Astrocytes (ieAstrocytes).

Biography

Research

Recent Blaho Lab News

Select Publications

HDL-bound sphingosine-1-phosphate restrains lymphopoiesis and neuroinflammation.

HDL-bound sphingosine 1-phosphate acts as a biased agonist for the endothelial cell receptor S1P1 to limit vascular inflammation.