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CANCER
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 Use
of Random Mutagenesis for Studies of Evolution and for Therapy
Manel Camps, Microbiology and Environmental Toxicology
The Camps laboratory uses molecular
genetic and computational approaches to study the biological
consequences of random changes in genetic information (mutations)
that occur spontaneously or as a result of environmental insults.
They couple the generation of random mutant libraries with specific
selections or screens to study the functional impact of point
mutations and to establish how genes evolve in response to selective
pressure. This work is relevant for the identification of risk factors
of disease, for understanding the origins of drug resistance, and for
engineering biological activities. The Camps laboratory also use induction
of random genetic alterations (mutagenesis) as an indicator of DNA
damage for high-throughput analysis of chemical libraries. Through
this approach, the Camps laboratory aims at exploiting the particular
susceptibility of rapidly replicating cells to DNA damage for therapeutic
purposes with the hopes of identifying candidates that complement or
enhance existing anti-tumor therapies. [More]
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 Marine
Natural Products as Anti-Cancer Compounds
Phil Crews, Dept. of Chemistry and Biochemistry
The Crews laboratory investigates
the chemical structure and biological activity of chemical compounds that are
derived from marine organisms. Among its many research projects, the laboratory
collaborates with scientists at other research institutions and pharmaceutical
industries to explore the identification and development of naturally occuring
compounds in the fight against cancer. [More]
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 How
Stem Cell Fate Is Decided
Camilla Forsberg, Dept. of Biomolecular Engineering
Camila Forsberg's research group focuses
on stem cell fate decisions that give rise to variant blood cell
types. Are such decisions made by the stem cell itself, by its descendant
multipotent progenitors, or both? To answer such questions, Forsberg's
group conducts molecular lineage tracing of HSC differentiation in
vivo. In order to elucidate the mechanisms of fate decisions,
they employ global analyses, such as genome-wide gene expression
analysis and chromatin remodeling assays. The ultimate goal of this
research is to facilitate our ability to direct specific fates and
improve clinical applications of hematopoietic and non-hematopoietic
stem cell therapy. [More]
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 Loss
of Growth Control and Cancer
Lindsay Hinck, MCD Biology
One in eight women in the United
States will develop breast cancer in her lifetime. Only about 15% of
these cancers have been linked to specific gene mutations; therefore
a major challenge in breast cancer research is to identify the causes
of the disease. We have identified Slits as breast tumor suppressors
that regulate several critical pathways controlling cell proliferation
and migration. Current research focuses on developing therapeutic strategies
to target these pathways. [More]
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 Lipoxygenase
Inhibitors as Potential Anti-Cancer Drugs
Ted Holman, Dept. of Chemistry & Biochemistry
Lipoxygenases are enzymes implicated in a broad range
of human cancers, as well as cardiac and inflammatory diseases. Ted Holman's
laboratory examines the enzymatic mechanism and biological function of lipoxygenase
in the hopes of developing novel inhibitors. In collaboration with UCSC Professor
Phil Crews, his laboratory has identified potent lipoxygenase inhibitors and
are currently characterizing their structure/function reactivity. The results
of this work will shed light on their potential as anti-cancer agents. [More]
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 Structure
and Functional Analysis of Spliceosomes
Melissa Jurica, MCD Biology
The Jurica lab uses the tools of structural biology
and biochemistry to investigate the cellular machinery responsible
for editing the information contained in the RNA transcripts of nearly
all of human genes. This machinery, called the spliceosome, splices
out intron sequences that interrupt gene transcripts and joins exon
sequences to make messenger RNAs that correctly encode for proteins.
The goal of Jurica's research is to understand how the spliceosome
is assembled and how it catalyzes the splicing reaction, but this is
..... [ More] |
 Mechanisms
that Control Cell Division and Cell Growth
Doug Kellogg, Dept. of MCD Biology
Cells show extraordinary diversity in size and
shape. The mechanisms by which cells control their growth and
size are poorly understood and represent a fundamental unsolved problem
in cell biology. The goal of the Kellogg laboratory's work is
to elucidate these mechanisms. Their approach is to use biochemistry,
genetics, and mathematical modeling to understand signaling networks
that are required for control of cell size and cell growth. [ More] |
 A
Small Molecule Approach for Studying Signaling Pathways Related to Cell Motility
and Cancer
Scott Lokey, Chemistry and Biochemistry
The laboratory of Scott Lokey uses
a small molecule approach, called chemical genetics, to study signaling pathways
related to cell cycle checkpoints and the actin cytoskeleton. In one study,
Lokey and his co-workers are developing screens of natural compounds that can
be used to examine how cells detect their own DNA damage. Studies such as these
might lead to development of a new class of chemotherapeutic agents. [More]
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 Light-Activated
Nitric Oxide Carriers: A New Path in Cancer Treatment
Pradip Mascharak, Chemistry and Biochemistry
Dr. Pradip Mascharak’s bioinorganic
chemistry laboratory conducts basic and applied research regarding metal-based,
nitric oxide (NO) carriers that release NO when activated by light. In
cancer cells, NO induces apoptosis (programmed cell death), which is the primary
cellular mechanism of tumor clearing in chemotherapeutic treatments. Unlike
conventional chemotherapy where the drug is distributed systemically, Mascharak’s
synthetic “NO donors” allow unique control over where, when, and
how much NO is released. This “photodynamic” approach has intriguing
implications for the development of drugs in treating skin and other cancers.
[More]
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 How
Bacterial Pathogens Sense and Respond to Host Environments
Karen Ottemann, Dept. of Microbiology and Environmental
Toxicology
Professor Karen Ottemann's laboratory investigates
how bacteria translate chemical and physical cues in their host environment
into adaptive responses. Mistakes in sensation and subsequent gene
expression by bacteria may result in their elimination by the host
immune response or peristaltic flow. Elucidation of such processes
will hopefully lead to identification of anti-bacterial drug targets.
Ottemann is particularly interested in the role of chemoreceptors
and chemotaxis associated with the bacterium Helicobacter pylori.
This pathogen infects some 3 billion humans and can lead to serious
disease, including ulcers and cancer. Ottemann and her colleagues
have discovered two of the first chemoreceptors known to aid in the
process of bacterial colonization. [More]
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 Molecular
Mechanisms of Cell Cycle Regulation and Cancer
Seth Rubin, Chemistry and Biochemistry
The Rubin laboratory uses a variety
of structural and biochemical techniques to investigate the molecular mechanisms
that control the eukaryotic cell cycle. The aim is to elucidate detailed molecular
pictures of protein-protein interactions and how these interactions are regulated
by structural and chemical modifications. Improper regulation of these protein
interaction networks is commonly associated with aberrant cell proliferation
and cancer. [More]
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 Assembly, Structure, and Regulation of the Telomerase Ribonucleoprotein
Michael Stone, Dept. of Chemistry and Biochemistry
The Stone Research Group combines
the use of biochemical and structural methods with newly emerging single-molecule
techniques to probe the dynamics of protein-nucleic acid interactions and the
molecular mechanisms of biological motors. Our current area of focus is
the structure and function of the telomerase ribonucleoprotein, an RNA-dependent
DNA polymerase that maintains genomic stability by synthesizing repetitive DNA
sequences at chromosome termini. These short DNA repeats provide the foundation
for specialized chromatin structures, called telomeres, which prevent deleterious
chromosome fusion events by differentiating chromosome ends from sites of DNA
damage. It has been shown that telomere length typically decreases with
every round of cell division, leading to the so-called ‘molecular clock’ hypothesis,
wherein telomere length serves as a signal to control cellular lifespan. This
notion is consistent with the finding that active telomere DNA synthesis is
normally restricted to rapidly dividing cell types such as stem cells and the
majority of human cancers. Our research seeks to elucidate physical mechanisms
governing telomere length regulation, and in turn establish a conceptual framework
within which to develop novel diagnostic and therapeutic strategies for human
disease. [More]
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 Cell
Cycle, Cytoskeleton and Pathogenesis
Bill Sullivan, Dept. of MCD Biology
The Sullivan lab uses the Drosophila embryo
as a model system to investigate the mechanisms that drive furrow
invagination during cytokinesis. Through a combination of cellular
and molecular genetic approaches, the Sullivan group has showed that
furrow formation requires coordinated cell cycle regulated and endocytic-based
vesicle recruitment. These studies have also identified a new role
for cell cycle checkpoints in coordinating the nuclear cycle with
cytokinesis. More recently, the lab has applied these approaches
toward understanding the mechanisms by which the widespread intracellular
insect pathogen, Wolbachia, influences host nuclear and
cytoplasmic cell cycles. [More]
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 Regulation
of Chromatin Structure and Gene Expression
John Tamkun, Dept. of MCD Biology
The Tamkun lab investigates regulation of
chromatin's high order structure and its role in gene expression.
Composed of DNA and proteins, chromatin's ability to fold enables
the eukaryotic genome to be packaged into an extremely small space
inside the nucleus of the cell. Proper transcription and replication
of the genome also depend upon precise regulation of these dynamic
structures, with defects in these processes believed to underly many
human diseases. [More]
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 The
Application of Molecular and Nanomaterial Systems to the Detection and Treatment
of Cancer
Jin Zhang , Dept. of Chemistry and Biochemistry
The Zhang research group is
interested in the application of molecular and nanomaterial systems in conjunction
with optical spectroscopy and related techniques for biomedical detection and
treatment, with emphasis on cancer therapies and cancer biomarker detection. Specific
projects include: 1) investigation of mechanisms of photodynamic therapy and
catalytic therapy based on porphyrins, phthalocyanines, and related compounds;
2) detection of small molecule, protein, and DNA cancer biomarkers using fluorescence
based on quantum dots (QDs) and surface-enhanced Raman scattering (SERS) based
on metal nanostrutcures; and 3) photothermal imaging and therapy of cancer using
unique metal nanostructures. This research involves systematic study of
the structural, optical, and photophysical as well as photochemical properties
of the materials using a combination of microscopy, x-ray, spectroscopy, and
electrochemistry techniques. [More]
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 Cellular
and Molecular Regulation of Antigen Presentation in Health and Disease
Martha Zuñiga, Department
of MCD Biology
The Zúñiga lab is interested
in the regulation of immune responses in health and disease. Major Histocompatibility
Complex (MHC) molecules (called HLA molecules in humans) present self, tumor,
and pathogen-derived antigens to the T cells. The presentation of MHC
molecules in different cellular contexts is of paramount importance in determining
immune responsiveness versus tolerance. One major project in the lab focuses
on mechanisms of immunological tolerance to cutaneous antigens. We have found
that skin-derived regulatory T cells can induce ..... [More]
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