Overview

Department Overview

Research of members of the Molecular and Cellular Biology Department focuses on elucidating the mechanisms underlying normal differentiation and development in mammals and understanding the genetic and epigenetic perturbations which disrupt that process. Such aberrations can manifest as cancer when regulatory mechanisms governing growth control are compromised.

The Department is located in the Medical Research Complex adjacent to the vivarium. Research programs of members make use of the powerful classical and molecular genetic approaches developed for use in the mouse that uniquely characterize it as the surrogate model system of choice for the study of human disease. This expertise is made available to other researchers at the Institute through collaborative interactions and the Gene Targeting and Transgenic Core Facility, which is operated and overseen by departmental staff members.

Currently work is focused in four thematic areas.

i)    The Analysis of Developmental and Cell Biological Control Mechanisms

      For example, this includes studies of:

·         Embryonic and somatic stem cell biologies (Pruitt).

·         Role of renin-agngiotensin system in renal vascular development (Gross).

·         Transcriptional mechanisms used by Hox genes in regulating immediate downstream target genes (Gross, Pruitt).

·         Molecular mechanism of circadian transcriptional control (Antoch).

·         Signal transduction cascades used by hematopoietic cytokines to regulate proliferation and differentiation (Baumann).

·         Mechanisms by which signal transduction pathways can serve as possible targets for therapy (Wenner).

·         The role of prostate-specific antigen (PSA) in modulating gene and protein expression of various angiogeneic growth factors in in vitro and in vivo prostate tumor models (Chadha).

·         The role of sialic acid and sialyltransferases during B cell development (Lau).

·         Role of circadian system in response to cancer therapy (Antoch).

ii)   Genetic Complex Trait Analysis of Cancer Susceptibility and Modifier Loci

      For example:

·         The identification of susceptibility loci for carcinogen-induced tumors in mice (Elliott, Demant).

iii) Analysis of Epigenetic Regulation of Gene Expression and Cancer Progression

      For example:

·         Use of restriction landmark genome scanning (RLGS) to investigate genetic and epigenetic alterations associated with human cancer and mouse models of tumorigenesis (Held).

·         Identification and analysis of genomic sites of developmental and tissue-specific DNA methylation (Held).

iv) Mouse Models of Cancer

      For example:

·         Analysis of genetic and epigenetic events accompanying progression in models of transgene-targeted oncogenesis (Held, Gross).