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Laboratories at Dartmouth College

This is a summary list of all laboratories at Dartmouth College . The list includes links to more detailed information, which may also be found using the eagle-i search app.

Ahmed Genetics Lab

Summary:

Our research uses Drosophila as a model to study the evolutionarily conserved Wnt/Wingless signal transduction pathway, with a focus on one component in this pathway, Adenomatous polyposis coli (APC). Wnt/Wingless signaling directs cell proliferation, cell fate, and apoptotic cell death during development and is inappropriately activated in several types of cancer. The majority of colorectal carcinomas have truncating mutations in APC, a negative regulator in Wnt signaling. APC functions in a protein complex that targets the key transcriptional activator in the pathway, beta-catenin, for proteasomal degradation. Thus inactivation of APC results in ectopic Wnt signaling, and the aberrant activation of target genes. The primary goals of our research are to determine the molecular mechanisms by which APC regulates Wnt signaling, and the molecular consequences of APC loss.



Barlowe Laboratory

Summary:

The research program is focused on understanding protein and lipid transport through the early secretory pathway in eukaryotic cells. This is an essential process that initiates the delivery of proteins to intracellular organelles and to the cell surface for secretion. Because of the advantage for genetic analyses, we investigate this process mainly in the yeast Saccharomyces cerevisiae. Our primary interest is elucidating the molecular mechanisms that underlie vesicular transport between the endoplasmic reticulum (ER) and Golgi complex. Transport between these compartments is mediated by membrane vesicles, termed COPII vesicles, that bud from the ER and fuse with and/or form the Golgi complex. Our studies combine molecular genetics, proteomics and microscopy with cell free assays that measure COPII-dependent transport. This cell free transport reaction proceeds through the biochemically distinct stages of COPII-dependent vesicle budding, Uso1p-dependent vesicle tethering and SNARE protein-dependent membrane fusion. We have reproduced these stages with isolated membranes and purified soluble molecules. A long-term goal of my research program is to reconstitute distinct sub-reactions in ER/Golgi transport with defined protein and lipid fractions for elucidation of catalytic mechanisms.



Barth & Smith Laboratory

Summary:

Breast Cancer Program
Cancer / Oncology
Endocrine Tumors Program
Gastrointestinal & Pancreatic Cancer Program
General Surgery
Melanoma / Skin Cancer Program
Surgical Oncology



Berwin Immunology Lab



Brinckerhoff Laboratory

Summary:

Dr. Brinckerhoff's laboratory studies Matrix Metalloproteinases (MMPs), enzymes with the traditional role of degrading the extracellular matrix, but also with new and novel functions that include activating receptors and growth factors, mediating apoptosis and facilitating angiogenesis. The focus is on the collagenases (MMP-1 and MMP-13) that mediate connective tissue destruction in arthritic diseases and that contribute to tumor invasion and metastasis. She and her colleagues are investigating the genetic and epigenetic mechanisms that regulate the over expression of these enzymes, with the goal of specifically blocking their aberrant expression and reducing disease pathology.



Calsbeek Evolutionary Ecology Lab

Summary:

Reproductive costs of the Anolis lizard, sexual conflict of the Anolis lizard, male-limited dorsal pattern polymorphism in anoles, experimental manipulations of whole island populations of the Anolis lizard to study natural selection.



Chang Biochemistry Laboratory

Summary:

Research interests include cholesterol trafficking and structure-function of cholesterol acyltransferase.



Chen Biology Lab

Summary:

Areas of expertise include ecotoxicology, aquatic ecology, and multiple stressors.



Cole Genetics Laboratory

Summary:

Research interests include fluorescence recovery after photobleaching (FRAP) to examine the dynamics of Dbp5, a DEAD-box protein at nuclear pore complexes and assembly and function of the nuclear pore complex (NPC) and the role of the nuclear envelope in NPC biogenesis.



Compton Laboratory

Summary:

Work in this lab is aimed at understanding how chromosomes segregate efficiently during mitosis and meiosis in vertebrate cells. Using both in vitro and in vivo approaches, the assembly and function of the microtubule-based spindle is being dissected at the molecular level. This work has led to the characterization of both structural and motor proteins that are necessary for the organization of the microtubules into spindles during mitosis and meiosis. Current work is aimed at how this process is regulated during the cell cycle and at how these proteins coordinate chromosome movement during cell division.



Computational Molecular Biology, Gene Regulation Laboratory



Dunlap and Loros Laboratories

Summary:

Our laboratories and research are directed towards understanding the mechanism by which eukaryotic organisms keep time on a daily basis, and how this capacity to keep time is used to regulate metabolism and development. Circadian clocks with fundamentally identical characteristics are found in all groups of eukaryotic organisms, but the uses to which these clock are put reflects the diversity of evolution. Phylogenetically this ranges from the control of cell division and enzyme activities in unicells, to a firmly established involvement in plant and animal photoperiodism and in avian and insect celestial navigation, to multiplicity of human systems including endocrine function, work-rest cycles and sleep, and drug tolerances and effectiveness. Cell division in many tissues and organs within the human body is regulated on a daily basis by the clock, providing the theoretical basis for chronotherapy of cancer, and manipulation of internal circadian rhythms provides treatments for several kinds of sleep and affective disorders. The general layout of the feedback loop that makes up the clock and the identity molecular identity of some of the components, particularly the heterodimeric positive elements WC-1 and WC-2 that serve as positive elements in the loop, appear to be conserved among the Crown Eukaryotes (Dunlap Science 280, 1548-49, 1998; Cell 96, 271-290, 1999).



Eastman Laboratory

Summary:

Research projects in Dr. Eastman's laboratory are focused on preclinical development of novel cancer chemotherapeutic strategies, using primarily established drugs in combination with novel therapeutic agents. Cancer cell lines exhibit very variable responses to these strategies, so it is predicted tumors will also have variable response such that some will be highly sensitive. The goal therefore is to define the mechanisms of sensitivity and develop clinical trials targeted to patients with sensitive tumors.



Enelow Microbiology and Immunology Lab

Summary:

Immunopathogenesis of respiratory virus infection., Inflammatory and immune-mediated lung disease., Influenza pathogenesis.



Fejes-Toth Physiology Lab

Summary:

The major research interest of Dr. Náray-Fejes-Tóth is the cellular and molecular mechanisms by which steroid hormones regulate kidney function and blood pressure.



Fiering Laboratory

Summary:

This lab investigates the function of various cis-regulatory DNA elements in controlling transcription during mammalian development. Our present focus is on the beta-globin locus and in particular, how expression of one gene at the locus suppresses expression of other nearby genes.

We are also interested in mouse models of cancer and are developing novel mouse models. The influence of tobacco smoke exposure on the innate immune system is another area of research in the lab.



Galton Laboratory

Summary:

Program in Experimental and Molecular Medicine



Gerngross Nanoparticle Targeting Laboratory

Summary:

Nanoparticle targeting focuses on using magnetic nanoparticles to destroy malignant tumors.



Gladfelter Laboratory

Summary:

We study how the cell cycle evolved to function in multinucleated cells. Single cells with many nuclei are found in bones and muscles, in fungal pathogens and in many cancers. We use two evolutionarily related fungi, the uninucleated budding yeast (S. cerevisiae) and a filamentous, multinucleated fungus (A. gossypii) to identify how the cell cycle machinery may have diverged to support accurate division within the spatial requirements of a multinucleated cell. These two related organisms are an excellent pair for such studies because while the genomes share about 95% of the same genes, approximately 100 million years have passed since their common ancestor allowing for significant divergence between homologues. We employ a broad range of experimental approaches including in vivo timelapse microscopy, cell biology, mathematical modeling, biochemistry and genetics to explore how cell cycle networks direct nuclear division within the unique geometry found in cells where many nuclei share one cytoplasm.



Green Microbiology and Immunology Lab

Summary:

The primary interests of the lab focus on cell-mediated immunity to mouse retroviruses that cause either leukemia or immunodeficiency.



Hogan Lab



Israel Genetics Lab

Summary:

On Id2 and Id4 - genes involved in embryo development and cancer, mouse models for the development and malignancy of brain tumors.



Kinlaw Laboratory

Summary:

Our research seeks to understand the peculiar metabolic needs of tumors, and how they adjust to them, with an eye toward exploiting tumor metabolism in the clinic. We have recently focused on the “addiction” of tumors, including breast cancers, to a supply of fatty acids. This has led to insights related to the regulation of lipid synthesis in tumors, and the ability to target it in preclinical systems and clinical trials. We recently found that tumors may not only synthesize fatty acids, but may also take them up from diet-derived lipoprotein particles in the circulation. Our laboratory has developed unique reagents to study these pathways, including novel antibodies and genetically engineered mice. We have also consistently focused on studies aimed to establish the relevance of our findings to actual human tumors, including breast and prostate cancers, sarcomas, and lymphomas, and are involved in clinical trials of the use of unusual fatty acids to manipulate these pathways inpatients. 0
Hanover NH 03755



Kisselev Laboratory

Summary:

The Kisselev laboratory works on fundamental and translational aspects of proteasome pharmacology, biochemistry, and cell biology. Proteins in all living cells are constitutively synthesized and degraded. The 26S proteasome is a large (2.5MDa) ATP-dependent proteolytic machine, which is responsible for the majority of protein degradation in mammalian cells. The majority of its substrates are damaged and misfolded proteins. Cancer cells, especially those which produce large amounts of proteins (e.g., antibody-secreting multiple myeloma cells), generate excessive amounts of abnormal proteins resulting in a high load on proteasome in these cells and making cancer cells highly sensitive to proteasome inhibitors. Peptide boronate inhibitor of proteasome Velcade (bortezomib) is being used for the treatment of multiple myeloma and mantle cell lymphoma, and five other proteasome inhibitors are now undergoing clinical trials.



Leib Lab

Summary:

Immunology Program, Molecular Pathogenesis Program, Molecular and Cellular Biology Graduate Programs



Lewis Laboratory



Miller Laboratory

Summary:

Research in the Miller Laboratory focuses on the translational application of knowledge of cell signaling pathways to therapeutics for breast cancer. Our work spans the spectrum of basic cancer biology, through translational studies in mouse models and human tissues, and interfaces with clinical trials. We use an array of methods and technologies both in our lab and through interaction with core facilities, including mammalian tissue culture, molecular analyses of gene and protein expression, gene expression microarrays, chromatin immunoprecipitation, next-generation DNA sequencing, bioinformatics, protein microarrays, mass spectrometry, mouse models, and live animal imaging.



Moseley Biochemistry Lab

Summary:

We study the basic mechanisms that coordinate cell growth and division. At the heart of this coordination are signaling pathways that link cell polarity proteins with the core cell cycle machinery. We use a multi-disciplinary approach to identify these pathways, and then to understand how their activities are controlled by changes in cell size and shape. As many of these proteins are found at distinct sites in the plasma membrane, we have also become interested in the organizational principles that generate discrete compartments at the cell cortex. For this work, we use fission yeast cells as a model system because they allow us to combine a wide range of genetic, genomic, biochemical, and microscopy techniques. In addition, the basic cell polarity and cell cycle systems are well conserved between fission yeast and human cells, where they have important links to the generation of cancer.



Mulligan-Kehoe Vascular Research Lab

Summary:

Heart and Vascular, Angiogenesis



Mullins Laboratory

Summary:

Our lab studies the molecular mechanisms that govern T cell infiltration of metastatic cancers. We translate our basic research findings into novel therapies that induce or augment immune cell infiltration of refractory tumors, thereby enhancing the clinical efficacy of immunotherapy.



Multimodal Neuroimaging Lab

Summary:

Research Interests
Biomedical imaging; functional neuroimaging; physiological modeling; heart rate variability; stroke recovery; Alzheimer's disease

Current Research Projects

Biomagnetometer instrument development
Clinical optical-electric probes
Functional biomarkers for Alzheimer’s Disease
Neurosimulator for electroencephalography
Neurovascular coupling
Wireless neural probes



Pogue Laboratory

Summary:

Biomedical optics and lasers; medical imaging; image guided spectroscopy of cancer; photodynamic therapy; modeling of tumor pathophysiology and contrast



Rzucidlo Heart and Vascular Research Lab

Summary:

Vascular smooth muscle cell differentiation

Professional Interests:
1) Intimal hyperplasia and restenosis of stents is like a cancer of the arteries.
2)Connective tissue growth factor (CTGF) has recently been described as a novel profibrotic factor.
3) Polymer-based drug eluting stents have drastically reduced restenosis. Issues related to potential tradeoffs between efficacy and safety has received increasing attention due to increased risk of late thrombosis.
4) Sirtiuns have long been considered the anti-aging target. Since aging leads to a progressive decline in multiple organ systems, including the pancreas and heart it is not surprising that sirtiun benefits are now being realized in diabetes and CVD.



Saito Genetics Laboratory

Summary:

Our lab uses C. elegans genetics, biochemistry, and cell biology techniques to reveal the mechanisms that direct cells to either divide or arrest during development. We are interested in this decision since cells that are unable to properly control cell divisions can result in developmental defects and cancer. To understand how the cell-cycle machinery is controlled in response to developmental signals we use the highly regulated cell divisions of C. elegans as a model system.



Sanchez Laboratory

Summary:

"Cells have evolved intricate networks of proteins or signal transduction pathways that allow them to integrate internal or external signals in order to respond to specific cues during development and during stress. Molecules that originate from neighboring cells, tissues, and pathogens, can act over short and long distances to elicit a physiological response. Signaling pathways can also be triggered within the cell, as is the case when cells are placed under alert following DNA damage or when there is a problem with DNA replication. Such information is transmitted via protein-protein interactions and protein modifications and leads to the alteration of gene expression and other events that regulate cell division, DNA repair or cell death. Our laboratory focuses on checkpoint signaling events triggered by DNA damage or replication interference. We are taking genetic, biochemical and cell biological approaches to study these signaling pathways. We are interested in dissecting signaling complexes involved in the response to lesions that are caused by DNA damaging agents or stalled replication forks and determining how specific protein-protein interactions and cellular location are regulated to transmit this information. We are also interested in the interactions between the signaling molecules and the enzymes that function in DNA replication and repair.

The pathways that we study are involved in both the etiology and treatment of cancer. Loss-of-function mutations in mammalian checkpoint genes compromise the response to DNA damage at the cellular level and at the level of the organism lead to a predisposition to cancer. In addition, cancer therapies frequently rely on drugs or agents that trigger genomic instability by taking advantage of the fact that cancer cells have defects in the response to DNA damage."

For a description of projects, see research: http://www.dartmouth.edu/~sanchezlab/



Schaller Biology Lab

Summary:

"We are interested in the mechanisms by which plants grow and respond to changes in their environment. Plants make use of a diverse group of signaling compounds to regulate growth and development. Although some of these compounds were identified almost a century ago, only recently has significant progress been made in identifying the proteins involved in sensing and transducing these signals. Much of this work has been accomplished by using the plant Arabidopsis, which serves as a model organism for addressing basic questions in plant biology. My laboratory uses a combination of biochemical, molecular, and genetic strategies to analyze signaling pathways in Arabidopsis."

Research projects:
1. Mechanism of cytokinin signal transduction in Arabadopsis
2. Mechanism of ethylene signal transduction in Arabadopsis



Shworak Laboratory



Spaller Lab

Summary:

The Spaller lab specializes in the study of protein-ligand and protein-protein interactions of biological and medicinal significance, focusing on those that regulate oncogenic and neuronal signal transduction pathways. Our efforts encompass aspects that are both fundamental—investigating the underlying molecular and cellular mechanisms—and applied—developing reagents that will serve as molecular probes in biological studies, or as compounds for use in drug development.



Stan Microbiology and Immunology Lab

Summary:

We are a cellular and molecular biology laboratory doing research focused on the molecular mechanisms of microvascular permeability. We are interested in both normal permeability and the changes it incurs in inflammation and angiogenesis in tumors and wound healing.



Surgical Research Laboratory (SRL)

Summary:

The Surgical Research Laboratory (SRL) is a bench laboratory and experimental OR research facility located in the Borwell building that originated more than 30 years ago.

The SRL is operated under the oversight of the Department of Surgery and is directed by P. Jack Hoopes DVM, PhD.

The SRL experimental animal operating suite includes state-of-the-art anesthesia delivery and monitoring, dedicated clinical fluoroscopy/angiography, ultrasound as well as a laser and ionizing radiation laboratory. The facility contains five permanent microsurgery operating microscope positions. Imaging modalities currently available for use include MRI, CT, PET, micro CT, ultrasound, fluoroscopy, bioluminescence and fluorescence imaging for large and small animal models. Expertise and instrumentation for endoscopy and laparoscopy are also available. An advanced intraoperative imaging facility has been funded and is under development.

Our bench laboratory plays an integral part in Dartmouth being designated as a Center of Cancer Nanotechnology Excellence (CCNE) with a grant from the National Cancer Institute (NCI). CCNEs are tasked with integrating nanotechnology into basic and applied cancer research in order to provide new solutions for the diagnosis and treatment of cancer. Our lab focus is on determining the optimal way to use alternating magnetic field-excited magnetic nanoparticle-mediated therapy to treat cancer, either as already confirmed in the breast/head and neck or as potentially unidentified multi-focal micro-metastases that remain after initial re-treatment. This project has both basic science and translational goals that will enhance the understanding of magnetic nanoparticle-mediated therapy, and also will explore crucial parameters that must be determined in order to design clinical trials.



Taub Laboratory

Summary:

Two main themes: understanding 1) the biological basis of spatial cognition and 2) the neurobiological mechanisms underlying learning and memory.



Taylor Lab

Summary:

Our work focuses on vaccine and drug development for prevention and treatment of epidemic cholera, which is spread aquatically in unhygienic conditions. Our current efforts involve interference with the production and function of a protein, TcpA, that forms specialized pili on the surface of the marine bacterium, Vibrio cholerae and facilitates infection of humans. The pili allow the bacteria to self-adhere, forming particles that become entrapped within the architecture of the human intestine where the bacteria release cholera toxin, causing severe, life-threatening diarrhea. The research encompasses studies on epitope specific protective immune responses as well as selective drug targets for cholera prevention. The studies are generally applicable to a number of serious infectious diseases such as meningitis, hemorrhagic colitis, sexually transmitted diseases, and infections associated with cystic fibrosis.



Tiltfactor Laboratory

Summary:

The Tiltfactor™ Laboratory is a conceptual design lab that researches, designs, launches, and publishes games and interactive experiences related to technology and human values.

We are a human-centered laboratory asking the big, important questions about where our technology is heading, and how we might improve it. Looking at gender and technology, empathy in games, novel educational methods, while influencing design processes to be more humanist in nature —focusing on human values and concerns—Tiltfactor is the place to think about how technology is meaningful, and how it can be designed for a more just, equitable, and innovative society.



Tomlinson Laboratory

Summary:

This lab has several research projects ongoing in the laboratory with the common theme of using high-throughput genomics approaches to study gene/environment interactions in development and disease

First, this lab studies the role of the aryl hydrocarbon receptor (AHR) in adult-onset cardiovascular disease (CVD). These studies are a test of the Barker hypothesis, which originated from epidemiological studies to explain the correlation between low birth rate and CVD, diabetes, obesity, and other adult onset diseases. The concept of the Barker hypothesis has been expanded to include in utero insults such as exposure to environmental agents that might influence developmental programs that adversely affect the fetus. The expanded Barker hypothesis, simply stated, is that an in utero stress; be it nutritional, chemical (drug or toxicant exposure), or physical; increases the likelihood that children borne of that mother will develop adult onset diseases and that this enhanced risk of disease is passed on to subsequent generations.

Using a mouse model system, they are testing the hypothesis that an in utero exposure of a toxicant to the fetus alters global AHR-regulated gene expression and genome-wide methylation patterns to reprogram the developing CV system resulting in heritable, trans-generational adult-onset cardiovascular disease. Thus, the primary objective of our work is to (1) correlate genome-wide methylation and global RNA expression profiles to identify those genes, signaling pathways, and developmental programs affected by a toxicant exposure during development that leads to an adult disease, and (2) determine whether the epigenetic changes in the developmental programs are inherited.

A second project in the lab is to develop new genomics technologies to examine all levels of gene expression (Fig. 3). The project involves the study of the global expression of RNA at the levels of transcription, the roles of DNA methylation in gene expression, the rates of nuclear and cytoplasmic RNA turnover, the accurate measurement of steady-state mRNA levels, and the regulation of polysome entry.

A third project in our laboratory is to determine the role of the AHR in mediating the effects of curcumin (and arsenic) on cystic fibrosis. Approximately 3,500 babies are born with CF annually, which dooms them to a drastically impaired lifestyle and reduced lifespan. Both curcumin (Fig. 4) and arsenic are ligands for the AHR. We culture human bronchial airway epithelia isolated from a ΔF508CFTR-/- patient (CFBE) and isogenic cells (CFBE+wtCFTR) complemented with the wild type cystic fibrosis transmembrane conductance regulator (CFTR). The CFBE and CFBE+wtCFTR cells are manipulated by siRNA methods such that the Ahr gene is expressed at either relatively high or low levels. A distinct advantage of using this strategy is that by virtue of the integral role the AHR plays in response to environmental agents, any corresponding differences observed in the inflammatory response and in gene expression and regulation profiles are due to the differing capacities of the AHR response. Thus, these studies are a superb means to study gene (Ahr) / environment (As or curcumin) interactions and their roles in lung inflammation.



Turk Immunology Laboratory

Summary:

Research in the Turk Laboratory focuses on understanding how the immune system responds to progressive, poorly immunogenic cancers. We are interested in CD8+ effector and memory T cells that are primed by progressive tumors, and the CD4+CD25+ regulatory T cells that suppress these anti-tumor immune responses. Our overall goal is to generate durable protective immunity in tumor-bearing hosts, without the use of active immunization (vaccines). We focus on manipulating the host’s own immune milieu during tumor growth to induce long-lived protection against recurrent and metastatic disease.



Usherwood Microbiology and Immunology Lab

Summary:

Generation and maintenance of T cell memory, immune therapies

The Usherwood lab has a long-standing interest in T cell immunity to viruses, particularly persistent virus infections. The large majority of the human population is infected by multiple persistent viruses. In some cases (HIV, Hepatitis C) this results in disease in all or a large proportion of those infected. However in many cases infection is clinically silent, and the infected individual suffers no adverse effects. In fact there is some evidence suggesting persistent infection may be beneficial in aiding the immune response repel other infections. During viral persistence there is a dynamic equilibrium between the virus and the immune response. One of our missions is to understand this interplay, and to determine the effect that the persistent infection has upon responding T cells, and conversely how the T cell response keeps the infection under control for very long periods of time. An important long-term goal of the laboratory is to develop immunotherapies that can restore immune surveillance in immune suppressed patients who suffer disease due to the loss of immune control of persistent infection. These immunotherapies could potentially also be useful in other conditions such as enhancing immune surveillance against tumor metastasis.

We use predominantly one persistent and one acute virus infection models in the lab:

Murine gammaherpesvirus 68 (MHV-68, γHV-68)



Van Citters Laboratory

Summary:

Research Interests

Orthopaedic failure analysis and design; wear of polymers; polymer processing; biomaterials and surgical device design

Current Research Projects:

Joint replacement technology
Orthopaedic biomaterials and tribology
Polymer Processing



Vincenti Laboratory

Summary:

Research in Dr. Vincenti's laboratory examines IL-1-dependent stimulation of MMP-1 in synovial fibroblasts and chondrocytes. These studies have established that IL-1 activation of the nuclear factor-kappa B (NF-κB) and the extracellular signal regulated kinase (ERK) pathways are critical processes for transcriptional activation of MMP-1 in these cells. Ongoing research is defining specific components of these pathways that are involved. Specifically, they have found that RelA and Bcl-3 are two NF-κB family members that are absolutely required for gene activation. Furthermore, IL-1 activation of the ERK pathway leads to phosphorylation of the transcription factor C/EBPβ, which directly binds to the MMP-1 promoter and facilitates transcription.

A second project in the laboratory investigates a group of plant-derived compounds known as triterpenoids. These compounds inhibit inflammation and reduce inflammation-induced MMP gene expression. TP-222, which is a triterpenoid that is highly bioavailable through oral administration to mice, effectively inhibits MMP-13 gene expression by chondrocytes and MMP-9 expression by osteoclasts. They are particularly interested in the molecular mechanisms through which TP-222 reduces MMP mRNA levels in these cells. It is hoped that this work will lead to the development of novel drugs that block cartilage destruction in arthritis and bone erosion in arthritis and osteoporosis.



Weaver Radiology Lab

Summary:

Interests include MR elastography, magnetic nanoparticle imaging, using magnetic nanoparticles as biomarkers for temperature and tissue stiffness, MR acquisition and pulse sequence development, digital image processing.



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