Undergraduate

Johns Hopkins University

Medical School

University of Chicago

Graduate

University of Chicago

Residency Training and Post-doctoral

Children’s Hospital, Boston; The Dana Farber Cancer Institute, Boston; and Harvard Medical School.

Our laboratory maintains a long-standing interest in myc oncoproteins. Three major members of medical importance include c-myc, N-myc and L-myc, which are amplified, chromosomally rearranged, or otherwise deregulated in diseases such as Burkitt’s and non-Burkitt’s lymphoma, breast cancer, neuroblastoma and lung cancer. Over the years, our laboratory has shown that overexpression of c-myc can inhibit cellular differentiation (1), alter cell cycle progression (2) and promote genomic instability (3). We also have recently shown that, in prostate cancer, c-myc function may be deregulated as a result of loss of a negative regulator of c-myc, termed Mxi1 (4).

We are currently utilizing DNA microarray technology as a way of comparing two samples by simultaneously monitoring the expression of over 6,000 genes. We have been applying this in an effort to identify genes that are deregulated as a result of c-myc overexpression. To date, a large number of candidate genes have been identified and their differential expression confirmed by Northern blotting. Characterization of these genes and the role they play in mediating the phenotype of c-myc overexpressing is ongoing. We are also extending this technology in order to identify differences in gene expression profiles between c-myc and L-myc-overexpressing cells and between cells that overexpress wild-type c-myc and mutant forms of c-myc which are unable to fulfill certain functions.

Program 2: Research on Oncogenes and Tumor Suppressor Genes

Our laboratory maintains a long-standing interest in myc oncoproteins. Three major members of medical importance include c-myc, N-myc and L-myc, which are amplified, chromosomally rearranged, or otherwise deregulated in diseases such as Burkitt’s and non-Burkitt’s lymphoma, breast cancer, neuroblastoma and lung cancer. Over the years, our laboratory has shown that overexpression of c-myc can inhibit cellular differentiation (1) and alter cell cycle progression (2). We have also shown that, in prostate cancer, c-myc function may be deregulated as a result of loss of a negative regulator of c-myc, termed Mxi1 (3). More recently, we have shown that overexpression of c-myc can promote genomic instability (4). This latter property is a hallmark of all naturally occurring and experimental cancers and is likely necessary in order for cancer cells to continuously to accumulate the mutations that contribute to such undesirable traits as metastasis and resistance to therapeutic agents. We are currently engaged in a series of studies aimed at better characterizing the means by which c-myc contributes to genomic instability. We are pursuing the roles of loss of the p53 tumor suppressor and elevated expression of cyclin B in this process.

Nature 322: 848, 1986.

Mol. Cell. Biol. 8: 3683, 1988.

Nature Genetics 9: 249, 1995.

Oncogene 18: 1177, 1999.