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Selected Publications

Representative publications on MRI of Gene Transcription

1. 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. (PMCID2647966)

[This manuscript describes innovative imaging of cerebral gene activities after amphetamine in the living brain using MRI via direct mRNA targeting by siDNA in neuron. The controls are non-targeting siDNA (randomized sequence) or MR contrast agent without siDNA in the same genetic background of mice; neither control has an mRNA target. The study was submitted for patent application (SN 60/603,907).]

2. 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. (PMCID2657320)

[This manuscript describes targeted MRI of cerebral gene activities in the living brain after cerebral ischemia; we showed that the targeting siDNA for neuronal cfos had specific bindings to mRNA in the neuronal formation of the dentate gyrus and was detected using in situ reverse transcription PCR. On the other hand, SPION-actin for actin mRNA exhibited uniform uptake for this housekeeping gene.]

3. 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¬. (PMCID2644455)

[In this study, we showed that the MRI-visible probe is retained by viable neurons and does not increase neurotoxicity, showing no change in water diffusion. We also demonstrated the uptake of the MR-visible probe (SPION-cfos) in the dentate gyrus with a resolution of 40 micron (2-3 cells)].

4. 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. (PMCID2648863)

[This manuscript describes delivery of MRI probes to the brain and in vivo cell typing by innovative delivery via intraperitoneal injection or eyedrop in live animals, bypassing the blood-brain barrier. We were able to detect new blood vessels with a diameter of 0.5 mm (angiogenesis after brain injury). The study was submitted for patent application (SN. 60-962,499).]

5. 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. (PMCID2726707)

[This manuscript describes in vivo theranostic application by multi-level detection of brain injury by hDWI/rADC, gene expression of Matrix Metalloproteinase-9 expression (diagnosis of abnormal protein using MR-visible siDNA in vivo) and potential gene knockdown of MMP-9 using siDNA (therapeutic application) in a cardiac arrest model of mice. The study was submitted for patent application (SN60-959,856).]

6. 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. (PMCID2746375)

[In this study, we investigated differential gene expression of two closely related genes using targeted MRI after acute and challenge paradigms of amphetamine exposure in live mice. We designed probes for FosB andDeltaFosB mRNA transcripts. The probe for FosB mRNA targeted the deleted region in DeltaFosB mRNA and gave null signal in the brain whereDeltaFosB mRNA is expressed. Patent application (SN60-959,878).]

7. Liu, CH., Ren, JQ., You, Z., Yang, JS., Liu, CM., Uppal, R and Liu. PK., Noninvasie detection of neural progenitor cells in living brains by MRI. FASEB J, in press, Dec 23 2011 (Accession No. 22198688)

[In this study, we demonstrated that intraperitoneal administration of specific MR contrast agent effectively revealed the presence of pericytes in new vessels formed in brain region after cerebral ischemia; the study holds promise as a strategy for monitoring progress of bone marrow-derived regenerative cells recruitment and retention at the site of injury and repair.]

Other Research Interests:

Imaging DNA Repair of the Central Nervous System:

  1. Mendez, D, Cherian L, Moore N, Arora T, Liu PK, Robertson CS. (2004) Oxidative DNA Lesions in a Rodent Model of Traumatic Brain Injury. J. Trauma, 56(6):1235-40
  2. Moore N, Okocha F, Cui JK, Liu PK. (2002) Homogeneous repair of nuclear genes after experimental stroke. J Neurochem. 80(1):111-8.
  3. Cui J, Liu PK. (2001) Neuronal NOS inhibitor that reduces oxidative DNA lesions and neuronal sensitivity increases the expression of intact c-fos transcripts after brain injury. J Biomed Sci. 8(4):336-41.
  4. Huang D, Shenoy A, Cui J, Huang W, Liu PK. (2000) In situ detection of AP sites and DNA strand breaks bearing 3'-phosphate termini in ischemic mouse brain. FASEB J. 14(2):407-17.
  5. Cui J, Holmes EH, Greene TG, Liu PK. (2000) Oxidative DNA damage precedes DNA fragmentation after experimental stroke in rat brain. FASEB J. 14(7):955-67.
  6. Lin LH, Cao S, Yu L, Cui J, Hamilton WJ, Liu PK. (2000) Up-regulation of base excision repair activity for 8-hydroxy-2'-deoxyguanosine in the mouse brain after forebrain ischemia-reperfusion. J Neurochem. 74(3):1098-105.
  7. Cui J, Holmes EH, Liu PK. (1999) Oxidative damage to the c-fos gene and reduction of its transcription after focal cerebral ischemia. J Neurochem. 73(3):1164-74.
  8. Gu ZZ, Pan YC, Cui JK, Klebuc MJ, Shenaq S, Liu PK. (1997) Gene expression and apoptosis in the spinal cord neurons after sciatic nerve injury. Neurochem Int. 30(4-5):417-26.
  9. Liu PK, Hsu GS. (1990)  On the DNA polymerase-a mutant: immunofluorescence assay of UV-induced thymidine dimers in Aphr-4-2 cells. Somat Cell Mol Genet. 16(1):49-57.
  10. Liu PK, Goudreau B, Hsu GS. (1989) Aphidicolin hypersensitive mutant of Chinese hamster V79 fibroblasts that underproduces DNA polymerase-alpha antigen. Somat Cell Mol Genet. 15 (4):331-44.

Genetic Therapy

  1. Cui JK, Hsu CY, Liu PK. (1999) Suppression of postischemic hippocampal nerve growth factor expression by a c-fos antisense oligodeoxynucleotide. J Neurosci. 19(4):1335-44.
  2. Liu PK, Kraus E, Wu TA, Strong LC, Tainsky MA. (1996) Analysis of genomic instability in Li-Fraumeni fibroblasts with germline p53 mutations. Oncogene.12(11):2267-78.
  3. Liu PK, Salminen A, He YY, Jiang MH, Xue JJ, Liu JS, Hsu CY. (1994) Suppression of ischemia-induced fos expression and AP-1 activity by an antisense oligodeoxynucleotide to c-fos mRNA. Ann Neurol. 36(4):566-76.
  4. Liu PK, Loeb LA. (1984) Transfection of the DNA polymerase-alpha gene. Science.226 (4676):833-5.

Molecular Basis of Mutation

  1. Liu PK, Hsu CY, Dizdaroglu M, Floyd RA, Kow YW, Karakaya A, Rabow LE, Cui JK. (1996) Damage, repair, and mutagenesis in nuclear genes after mouse forebrain ischemia-reperfusion. J Neurosci. 16(21):6795-806.
  2. Liu PK, Chang CC, Trosko JE, Dube DK, Martin GM, Loeb LA. (1983) Mammalian mutator mutant with an aphidicolin-resistant DNA polymerase alpha. Proc Natl Acad Sci U S A. 80(3):797-801.