Overview of Research Activities
The research interests of the Cell Biology and Genetics faculty comprise a wide range of topics related to the control of normal and malignant cell growth, differentiation, and tissue development. Purified proteins, isolated cells and tissues, and whole organisms are all being exploited as model systems, assisted by computational methods, genomics, and RNA profiling. Common themes throughout many of the research activities include the control of gene expression, signal transduction, cell growth and apoptosis, cell polarity and migration, stem cell biology, and cell-cell interactions.
Vascular biology and angiogenesis are topics with major emphasis within the program. Faculty conducting research in this area include Kathy Hajjar (receptor-mediated activation of surface proteases in the vasculature), Thomas Sato (angiogenic factors and receptors), Heidi Stuhlmann (vascular development and angiogenesis), David Lyden (tumor angiogenesis) and Shahin Rafii (regulation of of hematopoiesis by microvascular endothelium). In addition, Craig Basson is studying the molecular genetics of cardiovascular development, while Donald Fischman is interested in the development of cardiac and skeletal muscle.
The cell biology and genetics of cancer is a topic studied by several of the faculty. Robert J. Klein is interested in human cancer genetics, using computational approaches, while Raju Chaganti is focused on chromosomal and molecular alterations in cancer. Maria Jasin studies the repair of double strand DNA breaks, one of several forms of DNA damage relevant to cancer. James German studies Bloom's syndrome, a hereditary disorder of recombination; Ethel Cesarman's research concerns the role of viruses in human cancer, including KSHV.
Mouse models of human cancer provide an important tool for investigating this disease. Several such models are being developed in the laboratory of Harold Varmus, who is also studies aberrant signaling mechanisms in cancer. Eric Holland concentrates on mouse models of human brain cancer. Hans-Guido Wendel is interested in models of hematopoietic cancer and others, with an interest in developing novel therapeutics. RNA interference is one technique used for manipulating gene expression in these cancer models: its mechanistic basis is studied by Jidong Liu. The laboratory of Paul Marks has been developing drugs for differentiation therapy of cancer, such as histone deacetylase inhibitors. William Pao is investigating novel molecular therapeutics for lung cancer.
The control of cell proliferation (Robert Fisher) and apoptosis (Xuejun Jiang) are fundamental processes relevant to normal tissue development and disease, as is the control of differentiation by helix-loop-helix proteins (Robert Benezra) and transcriptional repressors (Yutaka Nibu). Cell signaling pathways regulate many of these functions and their misregulation contributes to tumorigenesis. Malcolm Moore investigates cytokines and other signaling pathways in hematopoietic cells and malignancies; Anthony Brown studies Wnt signaling mechanisms and their roles in early stage cancer. Neal Rosen is examining the role of tyrosine kinases in human breast and colorectal cancer, and Marilyn Resh studies the mechanisms of membrane binding and signaling by viral and cellular oncoproteins. Roger Gosden investigates mechanisms of fertility and the biology of the human egg.
The coordination of cellular signals by small GTPases is the focus of Alan Hall's research, which includes an emphasis on their role in polarized cell movement. Joel Pardee is also interested in cell motility, while Thomas Templeton is interested host tissue interactions in the life cycle of the malaria parasite Plasmodium, which is capable of various forms of cell movement. The laboratory of Joan Massagué studies TGF-
signal transduction and mechanisms of cancer cell metastasis to specific tissues. On a related topic, Johanna Joyce analyzes roles of the tumor microenvironment on cancer progression.
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Time-lapse projection image of "tip-tracking" along growing microtubules, monitoring EB1 protein. Sequential images at 5 second intervals were pseudo-colored in red, green and blue. (Kreizer lab)
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Epithelial cell and tissue biology is under investigation by several laboratories.
Enriqué Rodriguez-Boulan is involved in molecular and biochemical aspects of intracellular protein trafficking in polarized cells, while
Geri Kreitzer studies the kinesin family of proteins in epithelial polarization.
Monn Monn Myat focuses on multicellular epithelial morphogenesis in the development of glandular structures, using the Drosophila salivary gland as a model system. Integral to tissue morphogenesis are cell surface adhesion molecules such as integrins and cadherins, whose functions are studied by
Filippo Giancotti.
Carl Blobel's laboratory studies disintegrins, cell surface proteases relevant to growth factor signaling and tissue degenerative disorders such as rheumatoid arthritis.
Many of the faculty study aspects of cell biology in the nervous system. These include mechanisms of neuronal growth factor signaling (John Wagner), cell cycle regulation in neural precursor cells (Anna Marie Kenney), brain patterning and neural stem cell development (Tao Sun), and the molecular basis of notochord specification in ascidians (Anna Di Gregorio). Urs Rutishauser is analyzing the plasticity of cell interactions in the vertebrate nervous system, and Ching-Hwa Sung is investigating the molecular genetics and cell biology of retinal degeneration.
