Professor Hanson’s research group focuses on the application of synthetic organic chemistry to the development of new diagnostic and therapeutic agents for neoplastic diseases. He has more than 160 research publication and 12 patents and attracted over $15 million in research funding. Many of his projects involve joint efforts between his group and collaborators in medical centers in Boston and throughout the US. Current research projects include:
Development of Novel Radiotracers and Radiopharmaceuticals. The Hanson group developed the method for radiohalogenation via trialkylstannyl precursors. This method, first used in 1980 is the current standard for introducing most radiohalogens and radiocarbon groups onto aromatic compounds. The research group continues to develop methods for rapid labeling and purification of radiotracers and for preparing novel precursors for such labeling studies. One agent-Altropane NAV5001- is in Phase III clinical trials. Current areas of interest include growth factor receptor tyrosine kinase inhibitors, conventional and unconventional steroid hormone agonists and antagonists, integrin receptor ligands, prostate specific membrane antigen ligands and functionalized gold/organic nanoparticles.
Development of Novel Steroid Hormone Receptor Ligands. Our interest in steroidal derivatives represents 35 years of studies related to breast cancer research. The objectives include the development of diagnostic agents for the detection and evaluation of the disease, therapeutic agents for the treatment of the disease, and biochemical probes for understanding the disease. Within this broad program, we are currently exploring the effect of substitution at the 11ß-position of estradiol to determine the extent to which the receptor can undergo protein remodeling. In particular we are evaluating derivatives in which a second biologically active group can be appended at that site. Such materials would have two therapeutic effects that may act synergistically. We are also exploring whether the substituent effects observed in our studies with the estrogen receptor can be extended to other steroid hormone receptors, such as the androgen, progestin and glucocorticoid receptors.
Targeted drug delivery using multifunctional multivalent nanoparticles. Our research has developed a novel strategy for preparing multifunctional nanoparticles as a targeted drug delivery platform. Our approach utilizes our background in synthetic medicinal chemistry to prepare a variety of bifunctional chemo-orthogonal linkers which can be used to modify both the nanoparticle surface and a series of targeting, imaging, and therapeutic groups. Our selective convergent ligation methods then can systematically generate the multifunctional nanoparticles that can locate and treat specific tumor cells.
Proteomimetics. A new area of research in the Hanson group involves the design and synthesis of α-helical proteomimetics. Such materials display functional groups present in helical peptides but lack any central resemblance to a peptide core. The project involves identification of biological targets for which there is a helical peptide binding partner and the rational design of a 2- or 3-twist proteomimetics using computational methods. Our approach involves the preparation of a series of functionalized components that can be assembled using metal-catalyzed coupling reactions to give the final compounds. Biological evaluation by our collaborators provides the basis for iterative revision of the hypothesis, redesign and resynthesis.