Nancy Berliner

Professor of Internal Medicine (Hematology) and Genetics

B.A. Yale College, 1975
M.D. Yale Medical School, 1979

Research Interests:

Molecular Basis of Granulocyte Differentiation
Retinoid Responsive Genes in Myeloid Development

Honors:

American Cancer Society Junior Faculty Research Award
Leukemia Society of America Scholar
American Society for Clinical Investigation, Vice President, 1995
Interurban Clinical Club Membership
Stohlman Scholar, Leukemia Society of America, 1997
Arthur and Isabel Bunker Associate Professor of Medicine
Education Program Co-Chair, American Society of Hematology, 2000
Secretary, American Society of Hematology, 00-04

Our laboratory is primarily focused on the study of the control of gene expression in developing granulocytes. In the field of hematopoiesis, understanding of the molecular basis for the differentiation of myeloid cells has lagged behind the study of the maturation of the erythroid series, because of the difficulties in identifying satisfactory in vitro cell systems in which to study granulocytes. We have chosen to focus on this hematopoietic lineage in the hopes that through understanding of the normal processes of granulocyte maturation, we can gain insights into events that lead to the development of acute leukemia.

Current Research

We have chosen to study the neutrophil secondary granule, which arises at the myelocyte stage of neutrophil development, and is a definitive marker of terminal maturation of the neutrophil. We have cloned the cDNAs and genomic genes for the four major content proteins of the neutrophil secondary granule, and are investigating the mechanism governing coordinate stage-and tissue-specific expression of these genes during myeloid development.

More recent studies in the laboratory have been aimed at studying the earlier events in the granulocytic maturation pathway. We have characterized the differentiation of two murine hematopoietic cell lines carrying a dominant-negative retinoic acid receptor a, one of which is a multipotential cell line, and the other of which is a promyelocytic cell line. These lines exhibit a block to differentiation along the myeloid pathway, but undergo full, apparently normal, myeloid maturation in the presence of cytokines and high doses of retinoic acid. Using these cell lines, we have done analysis of differential gene expression to characterize those genes that are expressed in response to retinoic acid during early myeloid differentiation. In addition, as my interest has turned more toward the early events in myelopoiesis, I have also initiated studies of gene expression in hematopoietic stem cells. In collaboration with Dr. Ronald Hoffman, who has a program of research on hematopoiesis in large primates, we have undertaken to analyze differential gene expression comparing primary baboon stem cells derived from bone marrow, peripheral blood, and cord blood.

Representative Publications:

Khanna-Gupta, A., Zibello, T., Neufeld, E., Berliner, N. CCAAT displacement protein (CDP) recognizes a silencer element within the lactoferrin gene promoter. Blood 87:2091, 1997.

Lawson, N.D. and Berliner, N.Representational difference analysis of a committed myeloid progenitor cell line reveals evidence for bilineage potential. Proc. Natl. Acad. Sci. USA 95:10129-10133, 1998.

Lawson N, Khanna-Gupta A, Berliner N. Isolation and characterization of the cDNA encoding mouse neutrophil collagenase: Demonstration of shared negative regulation of neutrophil secondary granule protein gene expression. Blood, 91: 2517-2524, 1998.

Lawson ND, Berliner N. Neutrophil maturation and the role of retinoic acid. Exper Hematol. 27: 1355-1367, 1999.

Lawson ND, Zain M, Zibello T, Picciotto MR, Nairn AC, Berliner N. Modulation of a calcium/calmodulin dependent protein kinase cascade by retinoic acid during neutrophil maturation. Exper Hematol, 27: 1682-1690, 1999.

Khanna-Gupta A, Zibello T, Simkevich C, Rosmarin A, Berliner N. Sp1 and C/EBP are necessary to activate the lactoferrin gene promoter during myeloid differentiation. Blood 95: 3734-3741, 2000.

Updated 21 December 2000