Andrew M. Scharenberg, MD
Seattle Children's Attending Physician,
Immunodeficiency Clinic and Inpatient Immunology Service;
Professor, Pediatrics; Adjunct Professor, Immunology
Seattle Children's Research Institute
1900 9th Avenue
Seattle, WA 98101
Tel: (206) 987-7450
Dr. Scharenberg is a professor of pediatrics and immunology and co-director of the NGEC. His laboratory studies the role of ion channels in immune cell signal transduction and biology, and the application of homing endonucleases as tools for site-specific genome modification. Specific ongoing projects in his lab include studies of the role of Mg2+ transport in regulation of lymphocyte growth, directed evolution of homing endonucleases with novel recognition specificities, and molecular mechanisms of repair of nuclease-induced double strand breaks.
Dr. Scharenberg is currently the co-director of the NGEC and a principal investigator in the area of directed evolution of homing endonucleases.
Awards and Honors
- Alpha Omega Alpha, University of Michigan Medical School: 1988
- Denny Resident Award: 1992
- AAAAI Extramural Research Trust Award: 1996
- Fireman Fund Research Fellowship: 1999
- Hershey Prostate Cancer Award: 2000
- National Young Investigator Award, American Pediatric Society/Society for Pediatric Research: 2002
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
- 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
Overview of the Scharenberg Lab
Approximately half of the Scharenberg Lab works on directed evolution of homing endonuclease proteins, and their application to gene repair as part of the 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.
The Scharenberg Lab developed homing endonuclease surface display technology in collaboration with the Stoddard and Monnat Labs. The 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.
The major NGEC role of the Scharenberg Lab is to analyze homing endonuclease scaffolds received from the Monnat and Baker Labs. Scaffolds from the Monnat Lab will be newly identified and characterized “wild” homing endonucleases, or novel single chain enzymes created by the Monnat Lab. Scaffolds from the Baker Lab will have been computationally redesigned by the Baker Lab to recognize new target sites. The binding and cleavage properties of the scaffolds will be analyzed using homing endonuclease surface display technology.
By random introduction of mutations into the scaffold DNA coding sequences, the Scharenberg Lab will then generate large libraries of variant homing endonucleases. These libraries will be screened using homing endonuclease surface display technology for improvements in desired properties. This process can be iterated, resulting in the gradual “evolution” of the original scaffold towards new enzymes in which the desired properties have been optimized. This process is termed “directed evolution.”
The Scharenberg Lab is also working with the Rawlings Lab to develop murine XSCID and IPEX animal models to be used by the Rawlings Lab for its NGEC component, and with the Rawlings Lab and NGEC Cell and Viral Core to develop lentiviral expression vectors for use in gene repair experiments.
The Scharenberg Lab also seeks to develop platform technologies required for high throughput design and analysis of the binding and cleavage specificities of homing endonuclease.
Key personnel carrying out this research include Abigail Lambert (postdoctoral fellow), Mike Certo (graduate student), Kyle Jacoby (graduate student) and Sarah Baxter (graduate student).