Neuroscience Center at Massachusetts General
Massachusetts General Hospital –
Charlestown, MA 02129
Particular focuses are in molecular neuroscience and its relationship to gene activities during brain repair. My area of achievements include the first demonstration of somatic gene mutation in the brain after cerebral ischemia and I was awarded two R01 (NS034810 and NS045845) and two awards from American Heart Association. These awards lead to the development of brain probes with a potential to view gene action in live brains (R21NS057556). We have participated in at least three workshops sponsored by the NIH
I have developed a novel technique for magnetic resonance imaging (MRI) of gene transcripts in living subjects. This technique permits targeting, imaging, labeling and manipulation of intracellular gene transcript in live brains. As such, it represents an area of research that is poised to become the next frontier of MRI. The hospital has filed four patent applications based on our important inventions. The invention involves making a nanoparticle of less than 30 nanometers in diameter, and is composed of short nucleic acid (siDNA or siRNA) with sequence targeting specific messenger RNA (the target) and an MR contrast agent (tracer).
We have demonstrated that short DNA with proper sequence will target mRNA at low dose for non-invasive imaging using MRI; regulate protein expression at high dose for gene knockdown in the brain. We now have brain probes for angiogenesis, gliosis, and gender difference in gene activities of live brains. High resolution MR imaging of intracellular RNA for cell typing holds promises to translate molecular biology into live subjects for real time, longitudinal in vivo imaging. This design should have potential for pre-clinical and perhaps clinical applications, once it is validated for application in living brains of higher species than mice.
This ongoing work is supported byNINDS.
Laboratory for Gene Transcript Targeting, Imaging and Repair
here to access a PubMed search on Dr. Philip Liu
- Liu CH, Kim YR, Ren JQ, Eichler F, Rosen BR, Liu PK. Imaging cerebral gene transcripts in live animals. J Neurosci. 2007;27(3):713-22
- Liu CH, Huang S, Cui J, Kim YR, Farrar CT, Moskowitz MA, Rosen BR, Liu PK. MR contrast probes that trace gene transcripts for cerebral ischemia in live animals. FASEB J. 2007, 212(11)3004-15.
- Liu CH, Huang S, Kim YR, Rosen BR, Liu PK. Forebrain ischemia-reperfusion simulating cardiac arrest in mice induces edema and DNA fragmentation in the brain. Mol Imaging. 2007;6(3):156-167
- Liu, CH., You, Z., Ren, JQ. Kim, YR. Eikermann-Haerter, K. Liu, PK. Non-invasive delivery of MR contrast agents to live mouse brains for transcription MRI. FASEB J. 2008; 22:1193-1203.
- Liu, CH., You, Z., Liu, CM., Kim, YR., Whalen, MJ., Rosen, BR and Liu, PK*. Diffusion-Weighted MRI Reversal by Gene Knockdown of Matrix Metalloproteinase-9 Activities in Live Animal Brains J. Neurosci. 2009, 29:3508-3517.
- Liu, CH., Ren, JQ, Yang, J., Liu, CM, Mandeville, JB., Bhide, P., Yanagawa, Y., Rosen, BR and Liu, PK*., (2009) DNA-based MRI probes for Specific Detection of Chronic Exposure to Amphetamine in Living Brains. J. Neurosci., 29:1-663-10670, 2009