Samuel Achilefu, Ph.D.

Michel M. Ter-Pogossian Professor
Radiological Sciences
Internal Medicine
Biomedical Engineering

Biochemistry, Biophysics, and Structural Biology Program
Cancer Biology Program

Research Abstract:

Accurate and rapid detection of tumors is of great importance for assessing the molecular basis of cancer pathogenesis, preventing disease complications, and implementing a tailored therapeutic regimen. For these reasons, we design and develop new molecular probes and nanomaterials for imaging the expression of aberrant genes, proteins, and other pathophysiologic processes. To utilize optical methods for cellular and in vivo imaging by optical methods, we focus on developing materials that are fluorescent in the near-infrared and shortwave infrared (900-1700 nm) wavelengths of the electromagnetic spectrum where light can penetrate deep in thick tissue. Specific delivery of the contrast agents to target cells or tissue is accomplished by linking the molecules to bioactive molecules such as peptides, proteins, and drugs. Alternatively, the inherent chemical properties of the contrast agents provide a mechanism to monitor cell trafficking or physiological processes such as tissue hypoxia and ion transport in cells.

Another aspect of our program research involves the biological evaluation of the new drugs or materials to assess ligand trafficking in cells, cytotoxicity, cell proliferation, subcellular distribution, enzyme kinetics, and activation of specific molecular pathways in cells. In addition to proteases, we are also interested in detecting and monitoring the functional status of diagnostic kinases. We are also developing tissue-specific multi-modal imaging molecules that harness the strengths of optical with other imaging methods such as magnetic resonance and radionuclear (positron and single photon emission) imaging systems. Such multimodal imaging approach with multi-functional nanomolecules and nanoparticles will enable the full realization of the potential for noninvasive cellular and molecular imaging of pathologic tissues, including monitoring of drug action in vivo. For therapeutic interventions, we develop new drug molecules and new treatment methods, as well as convert our novel imaging agents into drug-delivery molecules to support targeted therapies. Part of these interventions includes tumor-specific Type I and II photodynamic therapy, a minimally invasive treatment paradigm.

A fundamental part of our work is the assessment of our new drugs and imaging agents in animal models of human diseases such as cancer. We utilize diverse imaging methods to determine the accuracy of detecting the target tissue or disease noninvasively using optical, photoacoustic, and nuclear imaging methods.

Finally, we translate our findings to human patients. For example, we developed Cancer Vision Goggles to aid surgeons to remove cancer accurately. A novel pan-cancer molecular probe is also undergoing clinical studies in cancer patients at the Siteman cancer center.
Our lab is equipped with state-of-the-art imaging systems (from cells to humans) and a multidisciplinary team of researchers (chemists, biologists, nanotechnologists, engineers, physicists, and clinical fellows and faculty). These lab-to-clinic multidisciplinary projects and collaborative research environment provide our students and fellows with in-depth training in a specific area of study while giving them the opportunity to engage in interdisciplinary training.

Selected Publications:

1. D. Shen, et al., "Selective imaging of solid tumours via the calcium-dependent high-affinity binding of a cyclic octapeptide to phosphorylated Annexin A2." Nat Biomed Eng 2020, 4 (3), 298-313.

2. C. Federico, et al., "Tumor microenvironment-targeted nanoparticles loaded with bortezomib and ROCK inhibitor improve efficacy in multiple myeloma." Nat Commun 2020, 11 (1), 6037.

3. J. Luan, et al., Ultrabright fluorescent nanoscale labels for the femtomolar detection of analytes with standard bioassays. Nat Biomed Eng 2020, 4 (5), 518-530.

4. R. Tang, et al. "Osteotropic Radiolabeled Nanophotosensitizer for Imaging and Treating Multiple Myeloma." ACS Nano 2020, 14 (4), 4255-4264.

5. C. O'Brien, et al., "Focal dynamic thermal imaging for label-free high-resolution characterization of materials and tissue heterogeneity." Sci Rep 2020, 10 (1), 12549.

6. A. Som, et al., "Calcium carbonate nanoparticles stimulate tumor metabolic reprogramming and modulate tumor metastasis." Nanomedicine (Lond) 2019, 14 (2), 169-182.

7. N. Kotagiri, et al., "Radionuclides transform chemotherapeutics into phototherapeutics for precise treatment of disseminated cancer." Nat Commun 2018, 9 (1), 275.

8. R.C. Gilson, et al., "Hybrid TiO(2) -Ruthenium Nano-photosensitizer Synergistically Produces Reactive Oxygen Species in both Hypoxic and Normoxic Conditions." Angew Chem Int Ed Engl 2017, 56 (36), 10717-10720.

9. N. Kotagiri, et al., "Breaking the depth dependency of phototherapy with Cerenkov radiation and low-radiance-responsive nanophotosensitizers." Nat Nanotechnol 2015, 10 (4), 370-9.

10. S. B. Mondal, et al., "Binocular Goggle Augmented Imaging and Navigation System provides real-time fluorescence image guidance for tumor resection and sentinel lymph node mapping." Sci Rep 2015, 5, 12117.

Last Updated: 3/22/2021 1:34:10 PM

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