Ph.D.

Professor Emeritus of Biochemistry

Biochemistry - School of Medicine

Director, MIC

Molecular Interactions Core

We have an established research program to develop radiolabeled peptides, proteins and nanoparticles as tumor specific diagnostic and therapeutic agents. Combinatorial peptide and antibody fragment libraries are being employed to identify molecules that preferentially bind tumor antigens. The tumor-avid peptides, antibody fragments and nanoparticles are subsequently engineered to bind the medically important radionuclides into their structures. Finally, the radiolabeled peptides, proteins and nanoparticles are investigated for their abilities to target tumor cells in vitro and in vivo in support of eventual clinical translation.

Radiolabeled Melanoma avid α-MSH Peptide Analogs: The goal of this project is to design radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs for melanoma imaging and therapy. α-MSH is a small tridecapeptide hormone that binds the melanocortin-1 receptor (MC1R) over expressed on melanoma tumor cells. Cyclic α-MSH peptide analogs have been synthesized and radiolabeled with ^99mTc, ¹¹¹In, ⁶⁴Cu and ⁶⁸Ga for melanoma imaging and ¹⁸⁸Re, ¹⁷⁷Lu and ²¹²Pb for melanoma therapy.

Melanoma Targeting Nanoparticles: In collaboration with Memorial Sloan Kettering and Cornell University, cyclic α-MSH analogs have been incorporated into ultrasmall (< 10 nm dia.) silica nanoparticles (C′ dots) for melanoma diagnosis, treatment and image-guided surgery. In pre-clinical melanoma animal models, the ¹²⁴I-α-MSH-C′ dots were shown to imaged melanoma tumors, while in therapy studies ¹⁷⁷Lu-DOTA-α-MSH-C′ dot treatment of melanoma bearing mice demonstrated significantly prolonged survival over control groups. Administration of α-MSH-C′ dots at high concentrations resulted in tumor cell death via a novel ferroptosis mechanism. The first generation of radiolabeled C′ dots for melanoma imaging and image-guided surgery have been translated into the clinic. Additional peptide and single chain antibody fragment (scFv) conjugated C′ dots are in the pipeline.

Tumor Binding Peptides and Antibody Fragments Selected from Bacteriophage Display Libraries: A combinatorial approach is being used to discover small peptides and single chain antibody fragments (scFvs) that bind the cancer associated Thomsen-Friedenreich (TF) glycoantigen, ErbB-2 receptor and matrix-metalloproteinase-12 (MMP-12) with high affinities and specificities from random peptide and scFv bacteriophage display libraries. Peptides that bound the TF and ErbB-2 were radiolabeled with ⁶⁴Cu and used to image tumors in murine breast cancer models. Recently, MMP-12 binding scFvs were radiolabeled with ⁶⁷Ga and shown to bind lung carcinomas. The MMP-12 scFvs were conjugated to the C′ dot nanoparticles, radiolabeled with ⁸⁹Zr and shown to exhibit superior imaging properties to radiolabeled scFv alone.

Educational background

• Ph.D. Molecular Virology, St. Louis University
• B.S. Biochemistry, University of Miami