Profile

Andrew M. Scharenberg, MD

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."

Andrew M. Scharenberg, MD, is attending physician at Seattle Children’s Hospital and is professor in the Department of Pediatrics and adjunct professor in the Department of Immunology at the University of Washington School of Medicine. He earned his MD with distinction from the University of North Carolina School of Medicine.

He completed residency training in pediatrics at the University of North Carolina Children’s Hospital and completed his fellowship in immunology at NIH and at the Division of Experimental Pathology, Beth Israel Hospital. He participates in the Seattle Children’s Immunodeficiency Clinic and the Inpatient Immunology Consult Service. At Seattle Children’s Research Institute, he operates a 12-member laboratory focused on lymphocyte physiology and gene repair of primary immunodeficiencies. Dr. Scharenberg is co-director of the Northwest Genome Engineering Consortium, a group of interdisciplinary investigators in the Seattle area working on genome engineering as a new approach to the treatment of inherited diseases. Through these activities, Dr. Scharenberg has a unique perspective on the potential for targeted gene repair in both primary and stem cell contexts, as well as the collaborative interdisciplinary interactions involved in carrying out 21st century research. He received the American Pediatric Society/Society for Pediatric Research National Young Investigator Award in 2002; and is an active member of the American Society for Clinical Investigation and the American Pediatric Society.

Making a Difference

Improving Tools for Gene Repair
Innovations in enzyme development move researchers in Seattle closer to making precision gene manipulation a therapeutic reality.
... cont.

A Thriving Biomedical Community

Partnering with UW and the Hutchinson Center for world-class science.... cont.

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Overview
Publications
Presentations

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
Lab URL: http://www.seattlechildrens.org/research/immunity-and-immunotherapies/ngec/
Research Focus Area: Immunology

Publications

TRPM7 regulates quiescent/proliferative metabolic transitions in lymphocytes.
Cell cycle (Georgetown, Tex.) , 2010 Sep: 3565-74

The BRCT domain of PARP-1 is required for immunoglobulin gene conversion.
PLoS biology , 2010 Jul 20: e1000428

Zinc-finger nucleases: a powerful tool for genetic engineering of animals.
Transgenic research , 2010 Jun: 363-71

High-resolution profiling of homing endonuclease binding and catalytic specificity using yeast surface display.
Nucleic acids research , 2009 Nov: 6871-80

Exploitation of binding energy for catalysis and design.
Nature , 2009 Oct 29: 1300-4

Structure/function analysis of PARP-1 in oxidative and nitrosative stress-induced monomeric ADPR formation.
PloS one , 2009 Jul 29: e6339

Immunologic reconstitution during PEG-ADA therapy in an unusual mosaic ADA deficient patient.
Clinical immunology (Orlando, Fla.) , 2009 Feb: 162-74

Optimization of in vivo activity of a bifunctional homing endonuclease and maturase reverses evolutionary degradation.
Nucleic acids research , 2009 Feb: 877-90

Characterization of parameters required for effective use of tamoxifen-regulated recombination.
PloS one , 2008 Sep 23: 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

TRPM7 ion channels are required for sustained phosphoinositide 3-kinase signaling in lymphocytes.
Cell metabolism , 2008 Jul: 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

Calcium signalling and cell-fate choice in B cells.
Nature reviews. Immunology , 2007 Oct: 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

SLC41A2 encodes a plasma-membrane Mg2+ transporter.
The Biochemical journal , 2007 Jan 15: 505-13

Flow cytometric analysis of DNA binding and cleavage by cell surface-displayed homing endonucleases.
Nucleic acids research , 2007: 2748-58

TRPML cation channels regulate the specialized lysosomal compartment of vertebrate B-lymphocytes.
European journal of cell biology , 2006 Dec: 1253-64

Metabolite of SIR2 reaction modulates TRPM2 ion channel.
The Journal of biological chemistry , 2006 May 19: 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

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: 373-8

TRPM2 and TRPM7: channel/enzyme fusions to generate novel intracellular sensors.
Pflugers Archiv : European journal of physiology , 2005 Oct: 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

Dual-function ion channel/protein kinases: novel components of vertebrate magnesium regulatory mechanisms.
Pediatric research , 2004 May: 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

Regulation of vertebrate cellular Mg2+ homeostasis by TRPM7.
Cell , 2003 Jul 25: 191-200

TRPM2 Ca2+ permeable cation channels: from gene to biological function.
Cell calcium , 2003 May-Jun: 519-31

Regulation of protein kinase Cnu by the B-cell antigen receptor.
The Journal of biological chemistry , 2003 Mar 14: 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

TRPM7 provides an ion channel mechanism for cellular entry of trace metal ions.
The Journal of general physiology , 2003 Jan: 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

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

TRPM4 is a Ca2+-activated nonselective cation channel mediating cell membrane depolarization.
Cell , 2002 May 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

A unified nomenclature for the superfamily of TRP cation channels.
Molecular cell , 2002 Feb: 229-31

Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation.
The Journal of experimental medicine , 2002 Jan 21: 189-200

Presentations

Presentations Title	Event	Location	Date
Flow Cytometry in Immunology: sample preparation, technology, applications	Allergy and Immunology Fellows Didactic Lecture, Seattle Children’s Research Institute	Seattle, WA	Nov. 1, 2009
Homing endonucleases as genome engineering reagents	UCLA Human Gene Medicine Program Symposium	Los Angeles, CA	June 1, 2009
Immune Reconstitution following NM-HCT	Mixed Chimerism Investigators’ Meeting, Fred Hutchinson Cancer Research Center	Seattle, WA	May 1, 2009
Common Variable Immune Deficiency: Overview and Case Studies	Allergy Journal Club, Center of Allergy and Inflammation	Seattle, WA	April 1, 2009
TRPM7 regulates quiescent-proliferative metabolic transitions in lymphocytes	Amgen Symposium	Seattle, WA	April 1, 2009
Engineered homing endonucleases for genome engineering applications	Cellectis SA, France	Paris, France	March 1, 2009

Primary Office

Seattle Children's Research Institute

C9S - 6 - Immunology
1900 - 9th Ave

Seattle, WA 98101

206-987-7450

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Andrew M. Scharenberg, MD

Making a Difference

Improving Tools for Gene Repair

A Thriving Biomedical Community

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Overview

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