Clinical diagnoses of genetic disorders are carried out by the clinical laboratories in the Division of Human Genetics, Department of Genetics and Developmental Biology. The cytogenetics laboratory provides chromosome analysis on peripheral blood, amniotic fluid cells, chorionic villus samples, bone marrow and solid tumors for pre- and post-natal genetic diagnosis. The Human Molecular Genetics laboratory provides DNA/RNA genetic testing on leukemia/lymphoma, breast cancer and other tumors, as well as a growing panel of genotyping tests for congenital genetic disorders. Molecular cytogenetics techniques, such as fluorescence in situ hybridization (FISH), are routinely performed. We serve the entire North and Central Connecticut and work closely with regional physicians.

The broad research interest of my laboratory is cancer genetics. We aim to employ current knowledge and advances in gene discoveries and functional analysis to identify biomarkers important for early diagnosis, prognosis, and therapeutic decision-making in cancer and to design clinical tests that can directly benefit patients. We have been studying the role of early growth response gene 1 (EGR1) in tumorigensis. EGR1 is a zinc finger transcriptioin factor that belongs to a multigene family that includes EGR2, EGR3, EGR4, and WT1. Available evidence suggests that the effects of EGR1 on tumorigenesis are critically dependent on the cellular context. In prostate cancer, EGR1 is overexpressed and its deletion significantly delays prostate tumor progression. In contrast, in other tumor types including breast cancer, skin cancer, glioblastoma/astrocytomas, and acute myeloid leukemia, EGR1 expression is often absent or repressed. Our data from studying epidermal hyperproliferative disorders including basal cell carcinoma and squamous cell carcinoma suggested that EGR1 exerts growth regulatory role through regulation of the G1/S transition of the cell cycle. In breast cancer, we found that EGR1 gene appeared to be deleted specifically in estrogen receptor-negative carcinomas. Currently, we are exploring the genetic differences between the ER-negative and ER-positive breast carcinomas on a genomic scale using comparative genome hybridization (CGH).

Another ongoing project is to understand the mechanisms of Gleevec resistance in chronic myeloid leukemia (CML) patients. A specific tyrosine kinase inhibitor, Gleevec is an FDA-approved drug that significantly improves the treatment of this disease. However, approximately 20% patients do not respond or develop resistance to Gleevec. Understanding the mechanism of such resistance may help develop additional therapies for CML.