Education
1978: Stanford University, BS
1984: Duke University, MD, PhD

Publications

Gross S, Gammon ST, Moss BL, et al. Bioluminescence imaging of myeloperoxidase activity in vivo. Nat Med. 2009;15(4):455-461.

Barnett EM, Zhang X, Maxwell D, Chang Q, Piwnica-Worms D. Single cell imaging of retinal ganglion cell apoptosis with a cell-penetrating, activatable peptide probe in an in vivo glaucoma model. Proc Natl Acad Sci U S A. 2009;106(23):9391-9396.

Kesarwala AH, Samrakandi MM, Piwnica-Worms, D. Proteasome inhibition blocks ligand-induced dynamic processing and internalization of EGFR via altered receptor ubiquitination and phosphorylation. Cancer Res. 2009;69(3):976-983.

Gammon ST, Villalobos VM, Roshal M, Samrakandi M, Piwnica-Worms D. Rational design of novel red-shifted BRET pairs: platforms for real-time single-chain protease biosensors. Biotechnol Prog. 2009;25(2):559-569.

Pichler A, Prior JL, Luker GD, Piwnica-Worms D. Generation of a highly-inducible Gal4

→ Fluc universal reporter mouse for in vivo bioluminescence imaging. Proc Natl Acad Sci U S A. 2008;105(41):15932-15937.

In the emerging post-genomic era, wherein functionality will be added to the expanding array of genetic information, opportunity exists for imaging to play a significant role in both basic and translational research as related to functional genomics. Herein, the objective is function through molecular imaging, which is broadly defined as the characterization and measurement of biological processes in living animals, model systems and humans at the cellular and molecular level using remote imaging detection methods, such as optical imaging (fluorescence, bioluminescence), positron emission tomography (PET), and magnetic resonance imaging (MRI). The overall goal is to advance the understanding of biology and medicine through noninvasive in vivo investigation of gene expression and molecular interactions in the context of the whole organism.

This laboratory has focused on three major lines of investigation in molecular imaging research:

*The development of imaging tools for investigating regulation of gene expression and protein function in vivo using firefly luciferases as bioluminescence reporters. When cloned into promoter/enhancer sequences or engineered into fusion proteins, imaging reporters enable fundamental processes such as transcriptional regulation, signal transduction cascades, protein-protein interactions, oncogenic transformation, cell trafficking and targeted drug action to be temporally and spatially registered in vivo. Exploiting mutant constructs of enzymes such as Herpes Simplex Virus-1 thymidine kinase as PET reporters also enables translation of projects into humans.

*The multidrug resistance P-glycoprotein, a 170 kDa plasma membrane protein encoded by the human multidrug resistance gene (MDR1), functions as an energy-dependent efflux pump of many compounds, including some of the most potent chemotherapeutic drugs in cancer treatment. Researchers in this lab have discovered gamma-emitting metallopharmaceuticals and bioluminescent substrates that are recognized as transport substrates by the P-glycoprotein to study the regulation and transport function of P-glycoprotein in living animals and patients.  The role of P-glycoprotein in beta-amyloid transport at the blood-brain-barrier is also under investigation.

*Researchers have explored the rapid and efficient delivery of fluorescent and radioactive metal complexes to the cell interior. Cell penetrating peptide conjugates incorporating transduction sequences and appropriate peptide-based motifs conferring functions of interest have been synthesized and validated as delivery vehicles. These novel peptide transduction conjugates can be readily derivatized for targeted applications in imaging and therapy as well as providing activatable probes of intracellular enzyme activities.