Cell nucleus, lamins, nuclear lamina


 

We study mechanical and rheological properties of the nucleus. In deciphering the structural and mechanical elements of the cell's nucleus we hope to determine roles of epigenetic regulation, stem cell differentiation, aging pathologies and cancer metastases. Mechanical regulation of cell and tissue function is poorly understood but is a fascinating area of study. Our research focuses on molecular, organelle, cellular and multicellular length scales over time, and we use a combination of spectroscopic, imaging, image informatics, biophysics and computational approaches.

 

 

 

 


Education

PhD 2004, University of Pennsylvania

Postdoctoral Training

Johns Hopkins University School of Medicine, Department of Cell Biology


 

Carnegie Mellon University
Department of Chemical Engineering
Doherty Hall 2100C
5000 Forbes Ave. 
Pittsburgh, PA 15213

Phone: (412) 268-9609 
Fax: (412) 268-7139

E-mail: krisdahl@cmu.edu 

Visit website 


 

High-resolution cryo-EM of macromolecular assemblies


Our research is focused on structure and function of macromolecular assemblies using three-dimensional cryo-electron microscopy (cryoEM), combined with biochemical, biophysical and molecular biology methods. CryoEM is a powerful tool for structure determination of large protein complexes and macromolecular assemblies, and their conformational changes to provide structural snapshots along dynamic processes. Research efforts in our lab are currently directed to two areas in biology: (I) HIV pathogenesis, particularly HIV capsid assembly, maturation, and interactions with host cell factors; (II) molecular mechanisms of signal transduction in bacterial chemotaxis. We are also developing technologies to bridge the gap in single molecule imaging, by integrating optical and electron imaging methods (correlative microscopy), and working at the interface of nanotechnology and biology.


Education

PhD 1998, University of Virginia, Molecular Biophysics

Postdoctoral Training

1998-2000 National Institute of Health, NIDDK
2000-2002 National Institute of Health, NCI


 

Department of Structural Biology
University of Pittsburgh
3501 5th Avenue
Pittsburgh, PA 15260

Phone: (412) 383-5907
Fax: (412) 648-8998

E-mail: pez7@pitt.edu

Visit lab website


 

Bioorganic chemistry 


 

Research in the Wipf Group focuses on the total synthesis of natural products, organometallic and heterocyclic chemistry, combinatorial, medicinal and computational chemistry. At the center of this research program is the study of chemical reactivity and the use of synthesis to augment the chemical toolbox and develop new therapeutic strategies. A major emphasis involves the efficient preparation of polyfunctionalized nitrogen-containing building blocks for biological screening and natural product target-directed synthesis. The discovery of fundamentally new reaction pathways is stimulated by exploratory studies of transition metal complexes, in particular zirconocenes.

 


 

Education

PhD 1987,University of Zürich, Switzerland

Postdoctoral Training

1988-1990, University of Virginia


 

Department of Chemistry
University of Pittsburgh
Parkman Avenue, CSC 1301
Pittsburgh, PA 15260

Phone: (412) 624-0787
Fax: (412) 624-8606

E-mail: pwipf@pitt.edu

Visit website


NMR of ion channels & low-affinity drug action


 

Research efforts in Dr. Xu's group are directed to three projects: (1); membrane protein structures and dynamics by NMR; (2); low-affinity drug interaction with membrane proteins, and (3); gene and stem cell therapy for brain protection and revitalization after cardiac arrest and resuscitation. The current focuses are as follows. For Project 1, NMR is used to determine the transmembrane domain structures of the human glycine receptor, which is the primary inhibitory receptors in the spinal cord and responsible for a wide range of diseases. The long-term goal is to provide the structural basis for novel design of drugs that are disease specific and devoid of side effects. For Project 2, experimental and theoretical approaches are combined to study how low affinity neurological agents, such as alcohol and general anesthetics, exert their effects on the central nervous system at the molecular level. The goal is to shed new lights on the great unsolved mystery of modern medicine: the molecular mechanisms of general anesthesia. For Project 3, new gene therapy strategies are being developed to target a special event called reperfusion injury after cardiac arrest and resuscitation. Recently, Dr. Xu's group combines gene therapy with stem cell therapy using a non-controversial source of stem cells, in an effort to stop and reverse the neuronal loss and to rebuild neuronal circuitry after reperfusion from prolonged cardiac arrest or stroke.

Students in Dr. Xu's laboratory have the opportunity to learn a variety of modern techniques, including expression and purification of membrane proteins, immunohistochemistry, high-resolution nuclear magnetic resonance imaging and spectroscopy, imaging reconstruction, 3-D protein structure calculation, and molecular dynamics simulations.

 

 


 
Education

PhD 1990, State University of New York

Postdoctoral Training

University of California at San Francisco

 

 


Department of Anesthesiology
University of Pittsburgh
Biomedical Science Tower 3, Room 2048
3501 Fifth Avenue
Pittsburgh, PA 15260 

Phone: (412) 648-9922 
Fax: (412) 648-8998

E-mail: xuy@anes.upmc.edu  

Visit website 


Structure-function studies of nucleotide excision repair proteins


 Structure-function Studies of Nucleotide Excision Repair Proteins. 
Faulty DNA repair can promote mutations, aging, cancer and cell death. The process by which protein components of repair detect damaged or modified bases within DNA is an important but poorly understood type of protein-DNA interaction. The cell contains a series of pathways designed to protect its DNA from environmental and endogenous damage. One of the most remarkable aspects of nucleotide excision repair (NER) is that it can remove a wide range of DNA lesions that differ in chemistry and structure. We are studying the structure, function and dynamics of bacterial NER proteins using a variety of approaches, including single-molecule techniques using Atomic Force microscopy, and TIRF microscopy. We seek to understand the structural motifs which these proteins use to recognize DNA damage and how these repair proteins sort through a sea of nondamaged DNA to find altered nucleotides.

Mitochondria and Disease:
Our group is testing the hypothesis that ROS generated in the mitochondria results in mtDNA damage causing a vicious cycle of damage: mtDNA damage causes a decrease in transcription and loss of essential mitochondrial proteins, causing a inhibition of electron transport and subsequent release in more ROS. This process causes further mitochondrial decline and many degenerative diseases associated with aging. We have developed a very sensitive DNA damage assay based on quantitative PCR that allows us to examine damage to nuclear and mitochondrial DNA from as little as 100 microliters of human blood. We are currently examining the role of mtDNA damage and repair in several human diseases including cancer and Friedreich's ataxia. Finally, we are assessing the bioenergetics of cancer cells by measuring oxidative phosphorylation and glycolysis.

  


 

Education

PhD 1984, Oak Ridge Graduate School of Biomedical Sciences, University of Tennessee

Postdoctoral Training

1984-1988, Lineberger Cancer Research Center, University of North Carolina


 

Department of Pharmacology & Chemical Biology
University of Pittsburgh
Hillman Cancer Center
5117 Centre Avenue
Research Pavilion, Suite 2.6
Pittsburgh, PA 15213-1863

Phone: (412) 623-7762
Fax: (412) 623-7761

E-mail: vanhoutenb@upmc.edu 

Visit website