Paul E. Neiman

Cellular and viral oncogenes
Normal and neoplastic B-cell development in the bursa of Fabricius
Functional genomic analysis of somatic genomic instability in cancer

The research in the Neiman laboratory, over the years, focussed generally on retroviruses and on normal and neoplastic development in the B-cell component of the immune system. The principal experimental system we exploited is the bursa of Fabricius in chickens. We demonstrated that bursal stem cells are selective targets in the B-cell lineage for the action of Myc oncogenes. Introduction of deregulated myc oncogenes into bursal stem cells in a transplantation assay developed in this laboratory, results in the proliferation of preneoplastic cells that are arrested at the bursal stem-cell stage of B-cell differentiation. Our work has included analysis of apoptotic
cell death in the bursa, which characterized little-studied Bcl-2 family members controlling bursal stem cell survival and follicular development. We developed tools for functional genomic analysis in this system and compared transcriptional signatures of normal embryonic bursal development with the preneoplastic and neoplastic stages of myc-induced lymphomagenesis. These studies demonstrated large neoplasia-associated transcriptional change, and a strong effect of the level of myc oncogene expression on the pattern of transcription. Comparison of bursal lymphomagenesis induced by Myc characterized similar neoplasms induced by two other transcription factors c-myb and v-rel. More recently, using array comparative genomic hybridiztion (Array CGH) and genome-wide analysis of pallindrome formation (GAPF), we examined aspects of genetic instabilty during Myc-induced lymphomagenesis . We discovered extensive DNA copy number change, principally amplification, and palindrome formation at early preneoplastic stages of tumorigenesis.

Currently, experimental work in the Neiman laboratory is being phased out. Dr. Neiman continues his interests through collaborative research with the Tapscott laboratory in Human Biology at FHCRC exploring GAPF-related technology for detecting genome-wide DNA palindrome formation and hyper methylation during human tumorigenesis.

An "Atlas of Normal and Myc-Induced Neoplastic Development in the Bursa of Fabricius", consisting of more than 100 down-loadable images, is freely available from a Hutchinson Center sponsored web site http://authors.fhcrc.org/368