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Andrew M. Scharenberg, MD

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Andrew M. Scharenberg, MD

Immunology

On staff since January 2001

Academic Title: Professor

Research Center: Center for Immunity and Immunotherapies

"As an immunologist, I primarily take care of patients with inherited immunodeficiencies. The patients on our service and their families typically have to deal with very significant impacts of the illness on their lives. I am continuously struck by the courage and perseverance they exhibit in adapting to their particular circumstances, and I draw on that every day to work a little harder, move a little faster, get a little better at providing the best possible care now as well as working to develop new, more effective, and less intrusive therapies."

Making a Difference

Overview

Board Certification(s)
Pediatrics
Medical/Professional School
University of North Carolina at Chapel Hill School of Medicine, Chapel Hill
Residency
Pediatrics, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill
Fellowship
National Institute of Health, Rockville
Clinical Interests

Primary / intestinal immune deficiencies

Research Description

Approximately half of the Scharenberg lab works on directed evolution of homing endonuclease proteins, and our application to gene repair as part of the Northwest Genome Engineering Consortium (NGEC). The other half works on the role of ion channels and 2nd messengers in immune cell biology, focusing on the channel/enzyme fusion proteins TRPM2 and TRPM7. Work in the latter area is spearheaded by Jaya Sahni on TRPM7, and Yumei Song and Ben Buelow on TRPM2 and ADP-ribose, respectively.

The Scharenberg lab developed homing endonuclease surface display technology in collaboration with the Stoddard and Monnat laboratories. Our lab uses surface display of homing endonucleases combined with both MACS and FACS for its work on the analysis and directed evolution of homing endonucleases.

The Scharenberg lab uses a wide variety of molecular and cellular biology methods, fluorescence imaging, flow cytometry, patch clamp, and mass spectrometry for its work on Mg2+ homeostasis and ADP-ribose 2nd messenger signaling functions.

Areas of expertise:
- Mg2+ homeostasis and role of Mg2+in biosynthetic metabolism
- 2nd messenger signaling functions of ADP-ribose
- Surface display and directed evolution of homing endonucleases

Current research interests:
- Role of Mg2+in the regulation of lymphocyte biosynthetic metabolism
- Role of ADP-ribose as an oxidative stress 2nd messenger
- Directed evolution of homing endonucleases

Research Focus Area

Immunology

Awards and Honors

Award NameAward DescriptionAwarded ByAward Date
MemberAmerican Pediatric Society (APS) 2010
MemberAmerican Society for Clinical Investigation (ASCI) 2008
American Pediatric Society/Society for Pediatric Research (APS/SPR) 2002
Hershey Prostate Cancer Award 2000
Fireman Fund Research Fellowship 1999
AAAAI Extramural Research Trust Award 1996
Denny Resident Award 1992
M.D. with Distinction 1990
Alpha Omega AlphaUniversity of Michigan Medical School 1988
B.S. summa cum laude with honors in BiochemistryIndiana University 1985

Publications

megaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering.
Nucleic acids research , 2013 Nov 26
Novel fluorescent genome editing reporters for monitoring DNA repair pathway utilization at endonuclease-induced breaks.
Nucleic acids research , 2013 Oct 10
Pillars article: Recruitment of tyrosine phosphatase HCP by the killer cell inhibitory receptor. Immunity. 1996. 4: 77-85.
Journal of immunology (Baltimore, Md. : 1950) , 2013 Oct 1: 191(7)3491-9
Characterization of three loci for homologous gene targeting and transgene expression.
Biotechnology and bioengineering , 2013 Aug: 110(8)2225-35
Genome engineering with TAL-effector nucleases and alternative modular nuclease technologies.
Current gene therapy , 2013 Aug: 13(4)291-303
The SLC41 family of MgtE-like magnesium transporters.
Molecular aspects of medicine , 2013 Apr-Jun: 34(2-3)620-8
Flow cytometric assays for interrogating LAGLIDADG homing endonuclease DNA-binding and cleavage properties.
Methods in molecular biology (Clifton, N.J.) , 2013: 97845-61
Coupling endonucleases with DNA end-processing enzymes to drive gene disruption.
Nature methods , 2012 Oct: 9(10)973-5
Engineering domain fusion chimeras from I-OnuI family LAGLIDADG homing endonucleases.
Nucleic acids research , 2012 Sep: 40(16)7985-8000
Engineered zinc finger nickases induce homology-directed repair with reduced mutagenic effects.
Nucleic acids research , 2012 Jul: 40(12)5560-8
Expanding LAGLIDADG endonuclease scaffold diversity by rapidly surveying evolutionary sequence space.
Nucleic acids research , 2012 Jun: 40(11)4954-64
Novel reporter systems for facile evaluation of I-SceI-mediated genome editing.
Nucleic acids research , 2012 Jan: 40(2)e14
The B. subtilis MgtE magnesium transporter can functionally compensate TRPM7-deficiency in vertebrate B-cells.
PloS one , 2012: 7(9)e44452
SLC41A1 Mg(2+) transport is regulated via Mg(2+)-dependent endosomal recycling through its N-terminal cytoplasmic domain.
The Biochemical journal , 2011 Oct 1: 439(1)129-39
Tapping natural reservoirs of homing endonucleases for targeted gene modification.
Proceedings of the National Academy of Sciences of the United States of America , 2011 Aug 9: 108(32)13077-82
Tracking genome engineering outcome at individual DNA breakpoints.
Nature methods , 2011 Jul 10: 8(8)671-6
Successful targeting and disruption of an integrated reporter lentivirus using the engineered homing endonuclease Y2 I-AniI.
PloS one , 2011 Feb 9: 6(2)e16825
Stable hematopoietic cell engraftment after low-intensity nonmyeloablative conditioning in patients with immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome.
The Journal of allergy and clinical immunology , 2010 Nov: 126(5)1000-5
TRPM7 regulates quiescent/proliferative metabolic transitions in lymphocytes.
Cell cycle (Georgetown, Tex.) , 2010 Sep: 3565-74
TRPM7 regulates quiescent/proliferative metabolic transitions in lymphocytes.
Cell cycle (Georgetown, Tex.) , 2010 Sep 1: 9(17)3565-74
The BRCT domain of PARP-1 is required for immunoglobulin gene conversion.
PLoS biology , 2010 Jul 20: e1000428
The BRCT domain of PARP-1 is required for immunoglobulin gene conversion.
PLoS biology , 2010 Jul 20: 8(7)e1000428
Zinc-finger nucleases: a powerful tool for genetic engineering of animals.
Transgenic research , 2010 Jun: 363-71
Zinc-finger nucleases: a powerful tool for genetic engineering of animals.
Transgenic research , 2010 Jun: 19(3)363-71
High-resolution profiling of homing endonuclease binding and catalytic specificity using yeast surface display.
Nucleic acids research , 2009 Nov: 6871-80
High-resolution profiling of homing endonuclease binding and catalytic specificity using yeast surface display.
Nucleic acids research , 2009 Nov: 37(20)6871-80
Exploitation of binding energy for catalysis and design.
Nature , 2009 Oct 29: 1300-4
Exploitation of binding energy for catalysis and design.
Nature , 2009 Oct 29: 461(7268)1300-4
TRPM2 and pancreatic -cell responses to oxidative stress.
Islets , 2009 Sep-Oct: 1(2)165-6
Structure/function analysis of PARP-1 in oxidative and nitrosative stress-induced monomeric ADPR formation.
PloS one , 2009 Jul 29: e6339
Structure/function analysis of PARP-1 in oxidative and nitrosative stress-induced monomeric ADPR formation.
PloS one , 2009 Jul 29: 4(7)e6339
Optimization of in vivo activity of a bifunctional homing endonuclease and maturase reverses evolutionary degradation.
Nucleic acids research , 2009 Feb: 877-90
Immunologic reconstitution during PEG-ADA therapy in an unusual mosaic ADA deficient patient.
Clinical immunology (Orlando, Fla.) , 2009 Feb: 162-74
Immunologic reconstitution during PEG-ADA therapy in an unusual mosaic ADA deficient patient.
Clinical immunology (Orlando, Fla.) , 2009 Feb: 130(2)162-74
Optimization of in vivo activity of a bifunctional homing endonuclease and maturase reverses evolutionary degradation.
Nucleic acids research , 2009 Feb: 37(3)877-90
Characterization of parameters required for effective use of tamoxifen-regulated recombination.
PloS one , 2008 Sep 23: e3264
Characterization of parameters required for effective use of tamoxifen-regulated recombination.
PloS one , 2008 Sep 23: 3(9)e3264
The Poly(ADP-ribose) polymerase PARP-1 is required for oxidative stress-induced TRPM2 activation in lymphocytes.
The Journal of biological chemistry , 2008 Sep 5: 24571-83
The Poly(ADP-ribose) polymerase PARP-1 is required for oxidative stress-induced TRPM2 activation in lymphocytes.
The Journal of biological chemistry , 2008 Sep 5: 283(36)24571-83
TRPM7 ion channels are required for sustained phosphoinositide 3-kinase signaling in lymphocytes.
Cell metabolism , 2008 Jul: 84-93
TRPM7 ion channels are required for sustained phosphoinositide 3-kinase signaling in lymphocytes.
Cell metabolism , 2008 Jul: 8(1)84-93
Development and validation of a cell-based high-throughput screening assay for TRPM2 channel modulators.
Journal of biomolecular screening : the official journal of the Society for Biomolecular Screening , 2008 Jan: 54-61
Development and validation of a cell-based high-throughput screening assay for TRPM2 channel modulators.
Journal of biomolecular screening , 2008 Jan: 13(1)54-61
Calcium signalling and cell-fate choice in B cells.
Nature reviews. Immunology , 2007 Oct: 778-89
Calcium signalling and cell-fate choice in B cells.
Nature reviews. Immunology , 2007 Oct: 7(10)778-89
Protein kinase D enzymes are dispensable for proliferation, survival and antigen receptor-regulated NFkappaB activity in vertebrate B-cells.
FEBS letters , 2007 Apr 3: 1377-82
Protein kinase D enzymes are dispensable for proliferation, survival and antigen receptor-regulated NFkappaB activity in vertebrate B-cells.
FEBS letters , 2007 Apr 3: 581(7)1377-82
SLC41A2 encodes a plasma-membrane Mg2+ transporter.
The Biochemical journal , 2007 Jan 15: 505-13
SLC41A2 encodes a plasma-membrane Mg2+ transporter.
The Biochemical journal , 2007 Jan 15: 401(2)505-13
Flow cytometric analysis of DNA binding and cleavage by cell surface-displayed homing endonucleases.
Nucleic acids research , 2007: 2748-58
Flow cytometric analysis of DNA binding and cleavage by cell surface-displayed homing endonucleases.
Nucleic acids research , 2007: 35(8)2748-58
TRPML cation channels regulate the specialized lysosomal compartment of vertebrate B-lymphocytes.
European journal of cell biology , 2006 Dec: 1253-64
TRPML cation channels regulate the specialized lysosomal compartment of vertebrate B-lymphocytes.
European journal of cell biology , 2006 Dec: 85(12)1253-64
Metabolite of SIR2 reaction modulates TRPM2 ion channel.
The Journal of biological chemistry , 2006 May 19: 14057-65
Metabolite of SIR2 reaction modulates TRPM2 ion channel.
The Journal of biological chemistry , 2006 May 19: 281(20)14057-65
Essential role for protein kinase D family kinases in the regulation of class II histone deacetylases in B lymphocytes.
Molecular and cellular biology , 2006 Feb: 1569-77
Essential role for protein kinase D family kinases in the regulation of class II histone deacetylases in B lymphocytes.
Molecular and cellular biology , 2006 Feb: 26(4)1569-77
Analysis of cellular Mg2+ in DT40 cells.
Sub-cellular biochemistry , 2006: 373-8
Calcium signaling, ion channels and more. The DT40 system as a model of vertebrate ion homeostasis and cell physiology.
Sub-cellular biochemistry , 2006: 257-70
Analysis of cellular Mg2+ in DT40 cells.
Sub-cellular biochemistry , 2006: 40373-8
Calcium signaling, ion channels and more. The DT40 system as a model of vertebrate ion homeostasis and cell physiology.
Sub-cellular biochemistry , 2006: 40257-70
TRPM2 and TRPM7: channel/enzyme fusions to generate novel intracellular sensors.
Pflugers Archiv : European journal of physiology , 2005 Oct: 220-7
TRPM2 and TRPM7: channel/enzyme fusions to generate novel intracellular sensors.
Pflugers Archiv : European journal of physiology , 2005 Oct: 451(1)220-7
Accumulation of free ADP-ribose from mitochondria mediates oxidative stress-induced gating of TRPM2 cation channels.
The Journal of biological chemistry , 2005 Feb 18: 6138-48
Accumulation of free ADP-ribose from mitochondria mediates oxidative stress-induced gating of TRPM2 cation channels.
The Journal of biological chemistry , 2005 Feb 18: 280(7)6138-48
Dual-function ion channel/protein kinases: novel components of vertebrate magnesium regulatory mechanisms.
Pediatric research , 2004 May: 734-7
Dual-function ion channel/protein kinases: novel components of vertebrate magnesium regulatory mechanisms.
Pediatric research , 2004 May: 55(5)734-7
Receptor-mediated regulation of the TRPM7 channel through its endogenous protein kinase domain.
Proceedings of the National Academy of Sciences of the United States of America , 2004 Apr 20: 6009-14
Receptor-mediated regulation of the TRPM7 channel through its endogenous protein kinase domain.
Proceedings of the National Academy of Sciences of the United States of America , 2004 Apr 20: 101(16)6009-14
BTK regulates PtdIns-4,5-P2 synthesis: importance for calcium signaling and PI3K activity.
Immunity , 2003 Nov: 19(5)669-78
The crystal structure and mutational analysis of human NUDT9.
Journal of molecular biology , 2003 Sep 12: 332(2)385-98
Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7.
Cell , 2003 Jul 25: 191-200
Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7.
Cell , 2003 Jul 25: 114(2)191-200
TRPM2 Ca2+ permeable cation channels: from gene to biological function.
Cell calcium , 2003 May-Jun: 519-31
TRPM2 Ca2+ permeable cation channels: from gene to biological function.
Cell calcium , 2003 May-Jun: 33(5-6)519-31
Regulation of protein kinase Cnu by the B-cell antigen receptor.
The Journal of biological chemistry , 2003 Mar 14: 9086-91
Regulation of protein kinase Cnu by the B-cell antigen receptor.
The Journal of biological chemistry , 2003 Mar 14: 278(11)9086-91
NUDT9, a member of the Nudix hydrolase family, is an evolutionarily conserved mitochondrial ADP-ribose pyrophosphatase.
The Journal of biological chemistry , 2003 Jan 17: 1794-801
NUDT9, a member of the Nudix hydrolase family, is an evolutionarily conserved mitochondrial ADP-ribose pyrophosphatase.
The Journal of biological chemistry , 2003 Jan 17: 278(3)1794-801
TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions.
The Journal of general physiology , 2003 Jan: 49-60
TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions.
The Journal of general physiology , 2003 Jan: 121(1)49-60
Analysis of O-acetyl-ADP-ribose as a target for Nudix ADP-ribose hydrolases.
The Journal of biological chemistry , 2002 Dec 6: 47114-22
Analysis of O-acetyl-ADP-ribose as a target for Nudix ADP-ribose hydrolases.
The Journal of biological chemistry , 2002 Dec 6: 277(49)47114-22
Activation of Syk tyrosine kinase is required for c-Cbl-mediated ubiquitination of Fcepsilon RI and Syk in RBL cells.
The Journal of biological chemistry , 2002 Oct 4: 36940-7
Activation of Syk tyrosine kinase is required for c-Cbl-mediated ubiquitination of Fcepsilon RI and Syk in RBL cells.
The Journal of biological chemistry , 2002 Oct 4: 277(40)36940-7
TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization.
Cell , 2002 May 3: 397-407
TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization.
Cell , 2002 May 3: 109(3)397-407
Dissociation of the store-operated calcium current I(CRAC) and the Mg-nucleotide-regulated metal ion current MagNuM.
The Journal of physiology , 2002 Mar 1: 445-58
Dissociation of the store-operated calcium current I(CRAC) and the Mg-nucleotide-regulated metal ion current MagNuM.
The Journal of physiology , 2002 Mar 1: 539(Pt 2)445-58
A unified nomenclature for the superfamily of TRP cation channels.
Molecular cell , 2002 Feb: 229-31
A unified nomenclature for the superfamily of TRP cation channels.
Molecular cell , 2002 Feb: 9(2)229-31
Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation.
The Journal of experimental medicine , 2002 Jan 21: 189-200
Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation.
The Journal of experimental medicine , 2002 Jan 21: 195(2)189-200
X-Linked Severe Combined Immunodeficiency
, 1993
Common Variable Immune Deficiency Overview
, 1993

Presentations

Presentations TitleEventLocationDate
High Efficiency Genome Editing Using Endonuclease/Exonuclease Co-expression2013 American Society of Gene Therapys (ASGCT) 16th Annual MeetingSalt Lake City, UTMay 2013
Genome Editing with Rare Cleaving Nucleases2012 American Society of Gene Therapys (ASGCT) 15th Annual MeetingMay 2012
Genetic Editing: The Key to Future Therapies for Genetic Disease, HIV, and CancerResearch in Action EventSeattle, WADec. 2011
Advanced Gene Modification TechnologiesExternal Scientific Advisory Board Meeting (EAB)Seattle, WAAug. 2011
Immune ReconstitutionMixed Chimerism Investigators MeetingSeattle, WAMay 2010
The role of BAFF in post-hematopoietic cell transplantation immune reconstitutionNovo Nordisk IncSeattle, WAMarch 2010
Flow Cytometry in Immunology: sample preparation, technology, applicationsAllergy and Immunology Fellows Didactic Lecture, Seattle Children’s Research InstituteSeattle, WANov. 1, 2009
Homing endonucleases as genome engineering reagentsUCLA Human Gene Medicine Program SymposiumLos Angeles, CAJune 1, 2009
Immune Reconstitution following NM-HCTMixed Chimerism Investigators’ Meeting, Fred Hutchinson Cancer Research CenterSeattle, WAMay 1, 2009
TRPM7 regulates quiescent-proliferative metabolic transitions in lymphocytesAmgen SymposiumSeattle, WAApril 1, 2009
Common Variable Immune Deficiency: Overview and Case StudiesAllergy Journal Club, Center of Allergy and InflammationSeattle, WAApril 1, 2009
Engineered homing endonucleases for genome engineering applicationsCellectis SA, FranceParis, FranceMarch 2009
Engineered homing endonucleases for genome engineering applicationsCellectis SA, FranceParis, FranceMarch 1, 2009
Recurrent Infections: An Immunologist's ViewNorthwest Allergy ForumSeattle, WAOct. 2008
The Northwest Genome Engineering Consortium and the Future of Gene RepairChildrens Legacy Planning CouncilSeattle, WAFeb. 2008
Design of novel LAGLIDADG homing endonucleases for genome engineering applicationsUW Institute for Stem Cell and Regnerative Medicine (ISCRM): Stem Cell MeetingSeattleNov. 2007
The Northwest Genome Engineering Consortium: new tools for manipulating genomes; new treatments for inherited diseaseBiotechnology and Biomedical Association (WBBA), Frontiers in Childrens HealthSeattle, WANov. 2007
Design of novel LAGLIDADG homing endonucleases for genome engineering applicationsUW Gene Therapy Club MeetingSeattle, WAOct. 2007
The Northwest Genome Engineering ConsortiumDWT Venture Series Seattle, WAOct. 2007
Signaling pathways downstream of the channel/kinase TRPM7FASEB Summer Research ConferenceSnowmass, COJune 2007
Use of multiparameter B-cell subset analysis for diagnosis and evaluation of humoral immunodeficienciesMolecular Diagnostic Center at Childrens Inauguration Seminar SeriesSeattle, WAMay 2007
Regulation of lymphocyte biosynthetic metabolism by TRMP7University of Washington 18th Annual Immunology Department RetreatPort Townsend, WASept. 2007
Dual Function Ion/Channel Kinases Regulate Cell GrowthFrontiers in Science/AMPSDC MeetingPhoenix, AZMarch 2006
TRPM2 and TRPM7 ion channels as drug targetsIBC Ion channels as drug targets conferenceBellevue, WAOct. 2005
TRPM ion channels as drug targetsAurora Biomed Conference on Ion channels and Transporters as Drug TargetsVancouver, BCJune 2005
Molecular mechanisms of Magnesium HomeostasisGordon Conference on MagnesiumVentura, CAFeb. 2005
Molecular Analysis of Mg2+ homeostasisUniversity of Toronto Neuroscience Group Seminar SeriesToronto, CANov. 2004
TRPM channel/enzymesGenentech post-doctoral fellow speaker series Feb. 2004
Mammalian Trp Channel as Molecular TargetsNobartis Foundation SymposiumLondon, UKMarch 2003
Ion channels as enzymes: structure and function of TRPM ion channelsPAS/SPR Meeting National Young Investigator AwardBaltimore, MD 2002
A novel family of cation channels expressed in immune system cellsAntigen Receptor SignalingSiena, ItalyApril 2000

Primary Office

Seattle Children's Research Institute
JMB - 6 - Immunology
1900 - 9th Ave
Seattle, WA 98101
206-987-7450

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