1. The evaluation of genetic screening

• Conducted the first studies of the benefits and burdens of New York State newborn sickle screening
• Demonstrated ready acceptance of genetic screening among members of an HMO, using beta-thalassemia trait as the test condition
• Showed that pregnant women detected to be hemoglobinopathy trait carriers generally had their partners tested to determine if their fetus was at risk
• Demonstrated that pregnant women detected to be cystic fibrosis carriers generally had their partners tested to determine if their fetus was at risk and, if so, usually wanted prenatal diagnosis. Conducted a cost-utility analysis of such screening.
• Showed that women coped well with the detection of a BRCA mutation provided that counseling before testing required them to plan what they would do with a positive or negative result.

2. The development of more effective anticancer agents by targeting the mutation initiating a given type of cancer. The ideal anticancer agent kills all tumor cells and no normal cells. Hence an agent should be directed toward the mutation initiating the cancer. Areas of investigation have included:

• antisense oligonucleotides targeting the bcr-abl translocation in chronic myeloid leukemia. Demonstrated that circular oligonucleotides are more effective than linear oligonucleotides because of their resistance to exonucleases.
• antisense peptide nucleic acids targeting the various chromosomal translocations in multiple myeloma. Showed that targeting the immunoglobulin enhancer inhibits expression of the oncogene juxtaposed to it by the translocation.
• double-stranded RNA inhibitors of telomerase. Demonstrated that encoding an RNA hairpin duplex provides long-term telomerase inhibition