Department of
Biological Chemistry & Molecular Pharmacology

Signal transduction

Alan D. D'Andrea

Professor
Telephone: 
617- 632-2112
Fax: 
617- 632-5757
Address: 
Room 640, Mayer Building, DFCI
Address: 
44 Binney Street
Address: 
Boston , MA 02115

Our laboratory examines the molecular signaling pathways which regulate the DNA damage response in mammalian cells. Disruption of these pathways, by germline or somatic mutation, leads to genomic instability, cellular sensitivity to ionizing radiation, and defective cell cycle checkpoints and DNA repair. These pathways are often disrupted in cancer cells, accounting for the chromosome instability and increased mutation frequency in human tumors.

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Michael Eck

Professor
Telephone: 
617-632-5860
Fax: 
617-632-4393
Address: 
Longwood Center, 4313
Address: 
360 Longwood Avenue
Address: 
Boston, MA 02215

Our laboratory studies the structural biology of cell signaling and the actin cytoskeleton. Active areas of investigation include: 1) the structure and regulation of focal adhesion kinase, 2) the molecular mechanisms that drive recruitment and activation of Src-family kinases in T-cell activation, and 3) formin proteins and the mechanisms by which they carry out the regulated assembly of actin structures. Additionally, we are studying other signaling interactions that may be targets for development of anti-cancer drugs. These include b -catenin/Tcf-4 and the interaction of transcription factor activation domains with p300/CBP.

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Elaine Elion

Professor
Telephone: 
617-432-3815
Fax: 
617-738-0516
Address: 
Room C1-302
Address: 
240 Longwood Avenue
Address: 
Boston MA 02115

Our group studies eukaryotic signal transduction, focusing on how external stimuli control proliferation, differentiation, and homeostasis. Work has centered on defining how mitogen activated protein kinase (MAPK) cascades function in vivo. MAPK cascades form the cores of numerous eukaryotic signal transduction pathways that control growth, differentiation and survival. Misregulation of MAPK cascades is associated with a variety of diseases, including cancer. We use a yeast model system (Figure 1) and genetic, biochemical and cell biological approaches.

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David Golan

Professor
Telephone: 
617- 432- 2256
Fax: 
617-432- 3833
Address: 
Room SGM - 304C
Address: 
240 Longwood Avenue
Address: 
Boston MA 02115

Our goals are to understand the molecular interactions controlling protein and lipid mobility and distribution in cell membranes, the roles these mechanisms play in interactions between cells, and the relationships between derangements in these mechanisms and the pathophysiology of disease. We have designed and constructed several time-resolved scanning laser microscopes for interactive monitoring, tracking, and manipulating of biological samples at the single-cell and single-molecule levels on the µs-ms time scale and nm distance scale. Using these instruments, we are investigating: 1) Molecular interactions in erythroid cell membranes.

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Ed Harlow

Professor

Research in the Harlow laboratory focuses on new approaches for functional analysis in mammalian cells. Our primary interest is learning how to do high throughput and unbiased screens for genes that affect key phenotypes of cancer biology. The levels of specific proteins can be increased or decreased by expressing the protein itself from a cDNA copy or by the introduction of an inhibitory RNA for the mRNA. We use libraries of individually cloned and sequenced full length coding regions and siRNAs to raise or lower protein levels in cells and study changes in cellular phenotypes. At present we have a complete proteome for several test organisms—bacteria Pseudomonas aeruginosa, the yeast Saccharomyces cerevisiae, and libraries for several viruses.

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Stephen C. Harrison

Professor
Telephone: 
617-432-5609
Fax: 
617-432-5600
Address: 
Room SGM - 130
Address: 
250 Longwood Avenue
Address: 
Boston MA 02115

We are structural biologists concerned with the organization and dynamics of macromolecular assemblies. We ask the following kinds of questions. (1) How do viruses assemble and get into and out of cells? (2) What are the molecular mechanisms of vesicular membrane traffic, particularly in the clathrin-coated vesicle pathway? (3) What is the molecular architecture of a kinetochore and how does this architecture embody its required mechanical and signal-transducing properties?

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Andrew Kruse

Assistant Professor
Telephone: 
617-432-3252
Address: 
Department of Biological Chemistry & Molecular Pharmacology
Address: 
Harvard Medical School
Address: 
240 Longwood Avenue
Address: 
Building C, Room 202
Address: 
Boston, MA 02115

Signal transduction across cell membranes plays a central role in human physiology and disease, yet the mechanistic details underlying transmembrane signaling remain poorly understood. Our research aims to elucidate the molecular basis of membrane protein signaling using techniques including protein engineering, structural biology, and pharmacology. In particular, we are focused on the study of proteins important in human health and disease, including G protein-coupled receptors and other proteins that regulate neurotransmission and metabolic homeostasis.

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Rosalind Segal

Professor
Telephone: 
617-632-4737
Fax: 
617-632-2085
Address: 
Dana-Farber Cancer Institute
Address: 
44 Binney Street
Address: 
Dana 620
Address: 
Boston, MA 02115

The research work in our laboratory has focused on growth factors that regulate survival and proliferation in the developing nervous system. These regulatory pathways are frequently disrupted in tumor formation or in neurodegeneration.

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Steven E. Shoelson

Professor
Telephone: 
617-732-2528
Fax: 
617-735-1970
Address: 
Dept. of Medicine
Address: 
Joslin Diabetes Center
Address: 
One Joslin Place
Address: 
Boston, MA 02115

Our studies can be divided into two main areas, (1) pathophysiological mechanisms of insulin resistance and type 2 diabetes, and (2) structural biology of diabetes and obesity. Type 1 or insulin-dependent diabetes is caused by insulin deficiency, in most cases due to autoimmune destruction of pancreatic beta cells. Fewer than 1 in 10 diabetics have this more severe form of the disease. Type 2 diabetes is much more common, and its prevalence is rapidly rising. Type 2 diabetes or NIDDM, affects greater than 10% of our population. In type 2 diabetes insulin is present, often in excess, but target tissues fail to respond appropriately. This is referred to as insulin resistance, a problem in signal transduction.

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Kevin Struhl

Professor
Telephone: 
617-432- 2104
Fax: 
617-432- 2529
Address: 
Room C1-315
Address: 
240 Longwood Ave.
Address: 
Boston, MA 02215

The molecular mechanisms of transcriptional regulation are highly conserved among eukaryotes. Transcriptional regulation in response to environmental and developmental cues is mediated by the combinatorial and synergistic action of specific DNA-binding activators and repressors on components of the general transcription machinery and chromatin modifying activities. Much of the work in this laboratory combines genetic, molecular, and genomic approaches available in yeast to address fundamental questions about transcriptional regulatory mechanisms in living cells. In addition, we are defining physiological targets of human transcriptional regulatory proteins and chromatin modifications on a whole-genome basis using a novel microarray approach.

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Morris F. White

Professor
Telephone: 
617-732-2578
Fax: 
617-732-2593
Address: 
Howard Hughes Medical Institute
Address: 
Department of Pediatrics, Division of Endocrinology
Address: 
Children's Hospital, New Research Building, Room 4210
Address: 
300 Longwood Ave.
Address: 
Boston, MA 02115

We investigate the molecular basis of insulin signal transduction to understand the pathophysiology of diabetes and related disorders, including obesity, infertility, and cardiovascular and retinal disease. Much of our work on signaling pathways that mediate the insulin response was fueled by our discovery of the insulin receptor substrate (IRS) protein family. Since diabetes is a complicated, multisystem disease, we use mice to integrate our molecular studies with physiology. Transgenic mice lacking the genes for Irs1 or Irs2 reveal a surprisingly close relation between the molecular regulation of insulin secretion and that of insulin action. We now understand that the IRS2-branch of the insulin/IGF signaling pathways controls pancreatic β-cell growth, function and survival.

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Hao Wu

Professor
Telephone: 
617-713-8160
Fax: 
617-713-8161
Address: 
Center for Life Sciences Boston (CLSB), Rm. 3099
Address: 
Three Blackfan Circle
Address: 
Boston, MA 02115

The Wu laboratory of structural immunology focuses on elucidating the molecular mechanism of signal transduction by immune receptors, especially innate immune receptors. The lab began its studies on the signaling of a classical cytokine produced by the innate immune system, tumor necrosis factor (TNF), which induces diverse cellular responses such as NF-κB activation and cell death. Receptors for TNF belong to the large TNF receptor (TNFR) superfamily. The second pursuit of the lab has been the Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily, which induces signaling pathways overlapping with those of the TNFR superfamily.

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