Neuron-Glia Interactions in Myelin Archives

Dr. Piña-Crespo earned a PhD in Pharmacology from University College London (UCL), England under the supervision of Profs. Alasdair Gibb & David Colquhoun FRS. He completed postdoctoral training as a Pew Fellow/Research Associate with Prof. Steve Heinemann in the Molecular Neurobiology Laboratory at The Salk Institute, La Jolla, California. Dr. Piña-Crespo has held faculty positions as Instructor and Assistant Professor at Universidad Centroccidental, Venezuela and as Lecturer in the Biology Department at the University of San Diego, California.

Education and Training

Postdoctoral training (Pew Fellow/Research Associate) The Salk Institute, California
PhD in Pharmacology University College London (University of London), England
Veterinarian (D.V.M.) Universidad Centroccidental Lisandro Alvarado, Venezuela

Honors and Recognition

Pew Fellow in the Biomedical Sciences

Related Disease
Aging-Related Diseases, Alzheimer’s Disease, Brain Injury, Epilepsy, Molecular Biology, Nervous System Injury, Neurodegenerative and Neuromuscular Diseases, Neurological and Psychiatric Disorders, Parkinson’s Disease, Stroke, Traumatic Injury

Phenomena or Processes
Aging, Apoptosis and Cell Death, Calcium Signaling, Cell Biology, Cell Signaling, Cell Surface Receptors, Development of Neuronal Circuits, Disease Therapies, Neurobiology, Neurogenesis, Neuron-Glia Interactions in Myelin, Neurotransmitters, Synapse Function, Synaptic Transmission

Anatomical Systems and Sites
Brain, General Cell Biology, Nervous System

Research Models
Cultured Cell Lines, Human Cell Lines, Human Embryonic Stem Cells, Mouse, Mouse Cell Lines, Primary Cells, Primary Human Cells, Rat, Vertebrates, Xenopus

Techniques and Technologies
Biophysics, Biophysiology, Calcium Imaging, Cellular and Molecular Imaging, Electrophysiology, Fluorescence Microscopy, Ion Channels, Live Cell Imaging, Mouse Behavioral Analysis, Pharmacology, Transplantation

Working on basic neuroscience discovery research. I use cellular and animal models of neurodegeneration to identify basic disease-causing mechanisms and disease-relevant targets involved in abnormal neuron-glia signaling, synapse failure, neuronal network dysfunction and neuronal loss in age-related neurodegenerative diseases; including Alzheimer’s and Parkinson’s disease. Extensive hands-on experience working and managing projects that require a strong background in in-vitro, ex-vivo and in-vivo neuroscience, pharmacology and electrophysiology.

Neuroscience Discovery Research

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Showing 2 of 2

Trem2 deletion enhances tau dispersion and pathology through microglia exosomes.

Zhu B, Liu Y, Hwang S, Archuleta K, Huang H, Campos A, Murad R, Piña-Crespo J, Xu H, Huang TY

Mol Neurodegener 2022 Sep 2 ;17(1):58

High-frequency hippocampal oscillations activated by optogenetic stimulation of transplanted human ESC-derived neurons.

Piña-Crespo JC, Talantova M, Cho EG, Soussou W, Dolatabadi N, Ryan SD, Ambasudhan R, McKercher S, Deisseroth K, Lipton SA

J Neurosci 2012 Nov 7 ;32(45):15837-42

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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.

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Showing 2 of 2

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

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Timothy Huang completed his PhD at the University of Calgary (Canada) under Dr. Dallan Young, studying kinase pathways involved in mediating cell polarity in yeast. He studied mechanisms underlying actin cytoskeletal dysfunction in Alzheimer’s disease at Scripps with Dr. Gary Bokoch (La Jolla), before joining Dr. Huaxi Xu’s laboratory in 2012/2013.

Related Disease
Alzheimer’s Disease, Molecular Biology

Phenomena or Processes
Cell Biology, Cell Signaling, Neurobiology, Neurodegeneration, Neurogenesis, Neuron-Glia Interactions in Myelin, Proteolytic Pathways, Tyrosine Kinases

Anatomical Systems and Sites
Brain

Research Models
Human, Human Cell Lines, Mouse, Mouse Cell Lines

Techniques and Technologies
Biochemistry, Cellular and Molecular Imaging, Confocal Microscopy, Electrophysiology, Mass Spectrometry, Protein Engineering, Protein-Protein Interactions, Protein-Small Molecule Interactions, Proteomics

My research is focused on identifying and characterizing mechanisms of neurodegeneration in Alzheimer’s disease (AD) and other related neurodegenerative disorders, and identifying neuroprotective pathways that may be involved in slowing disease progression. Currently, my research is focused on the genetic AD risk factors SORLA (SORL1, LR11) and TREM2, which may be involved in attenuating pathogenic effects associated with cognitive decline. By implementing methods to enhance these neuroprotective pathways, we may be able to reverse neuronal and cognitive damage in AD, and possibly other associated disorders.

Timothy Huang’s Research Report

There are two projects that comprise my main focus: 1) SORLA: Sortilin-related receptor with LDLR class A repeats (SORLA, SORL1, or LR11) is a genetic risk factor associated with Alzheimer’s disease (AD). Although SORLA is known to regulate trafficking of the amyloid β (Aβ) precursor protein to decrease levels of proteotoxic Aβ oligomers, whether SORLA can counteract synaptic dysfunction induced by Aβ oligomers remains unclear. Our work indicates that SORLA interacts with the EphA4 receptor tyrosine kinase and attenuates ephrinA1 ligand–induced EphA4 clustering and activation to limit downstream effects of EphA4 signaling in neurons. Consistent with these findings, SORLA transgenic mice, compared with WT mice, exhibit decreased EphA4 activation and redistribution to postsynaptic densities, with milder deficits in long-term potentiation and memory induced by Aβ oligomers. Importantly, we detected elevated levels of active EphA4 in human AD brains, where EphA4 activation is inversely correlated with SORLA/EphA4 association. These results demonstrate a novel role for SORLA as a physiological and pathological EphA4 modulator, which attenuates synaptotoxic EphA4 activation and cognitive impairment associated with Aβ-induced neurodegeneration in AD. 2) TREM2: Although ligands for TREM2 such as ApoE have been previously identified, a definitive mechanism for TREM2 in AD has not been established. We recently determined that TREM2 directly binds Aβ oligomers with nanomolar affinity and R47H mutations attenuate TREM2/Aβ interaction. TREM2 deletion impairs Aβ turnover in primary microglia, and abrogates Aβ clearance in vivo. Aβ also triggers changes in microglial membrane potential which is impaired with TREM2 deletion. Moreover, TREM2 deletion attenuates Aβ-induced microglial morphogenic changes associated with activation, and inhibits Aβ-mediated induction of proinflammatory cytokine expression. Together, these results indicate that TREM2 may have opposing neuroprotective roles in mediating microglial Aβ clearance and turnover, while concurrently transducing potentially neurotoxic Aβ-induced inflammatory signals. To further define a role for TREM2 in Aβ clearance and Aβ-mediated microglial activation/cytokine expression, we plan to exploit use of TREM2 R47H knock-in and TREM2 WT and R47H overexpression mouse models currently housed in our laboratory to determine whether impaired TREM2/Aβ interactions can impair microglial response in the presence of Aβ. This provides essential groundwork in future strategies to optimize neuroprotective TREM2 Aβ clearance while limiting Aβ-induced microglial inflammation.

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Showing 2 of 2

SORLA attenuates EphA4 signaling and amyloid β-induced neurodegeneration.

Huang TY, Zhao Y, Jiang LL, Li X, Liu Y, Sun Y, Piña-Crespo JC, Zhu B, Masliah E, Willnow TE, Pasquale EB, Xu H

J Exp Med 2017 Dec 4 ;214(12):3669-3685

Multi-omic comparison of Alzheimer’s variants in human ESC-derived microglia reveals convergence at APOE.

Liu T, Zhu B, Liu Y, Zhang X, Yin J, Li X, Jiang L, Hodges AP, Rosenthal SB, Zhou L, Yancey J, McQuade A, Blurton-Jones M, Tanzi RE, Huang TY, Xu H

J Exp Med 2020 Dec 7 ;217(12):

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Phenomena or Process: Neuron-Glia Interactions in Myelin

Education and Training

Honors and Recognition

Select Publications

Trem2 deletion enhances tau dispersion and pathology through microglia exosomes.

High-frequency hippocampal oscillations activated by optogenetic stimulation of transplanted human ESC-derived neurons.

Anne Bang’s Research Report

Publications

Patents

Select Publications

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.

Timothy Huang’s Research Report

SORLA attenuates EphA4 signaling and amyloid β-induced neurodegeneration.

Multi-omic comparison of Alzheimer’s variants in human ESC-derived microglia reveals convergence at APOE.

Biography

Education and Training

Honors and Recognition

Research

Select Publications

Trem2 deletion enhances tau dispersion and pathology through microglia exosomes.

High-frequency hippocampal oscillations activated by optogenetic stimulation of transplanted human ESC-derived neurons.

Biography

Research

Select Publications

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.

Biography

Research

Select Publications

SORLA attenuates EphA4 signaling and amyloid β-induced neurodegeneration.

Multi-omic comparison of Alzheimer’s variants in human ESC-derived microglia reveals convergence at APOE.