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Training Faculty
- Daniel Donoghue, PROGRAM DIRECTOR
Regulation and activation of receptor tyrosine kinases; FGFR mutations
in multiple myeloma and other cancers; cyclin-like proteins and control
of cell cycle regulation.
- Karen Arden
Forkhead (FOXO) family transcription factors and their importance in
cancer; mammalian cancer genetics.
- Gerry Boss
Ras activation in breast, lung and prostate cancers using a novel
enzyme-based method; importance of the Ras-related proteins, Rap 1
and Rho, in human tumors; mechanism of nitric oxide (NO) regulation of
vitamin B12 (cobalamin)-dependent reactions such as methionine synthase.
- Michael Burkart
Natural product biochemistry, and organic synthesis and derivatization
of antitumor compounds; assessment of these molecules as improved
therapeutics using biosynthetic pathways of individual enzyme systems
that act on precursors and/or derivatives of antitumor molecules.
- David Cheresh
Tumor angiogenesis, tumor cell invasion and metastasis; molecular
mechanisms that regulate tumor cell and endothelial cell survival,
migration and invasion; role of alpha V integrins and their ligands
in regulation of the epithelial to mesenchymal transition; disruption
of angiogenesis and tumor growth by small molecule Raf kinase pathway
inhibitors.
- Michael David
JAK/STAT signaling; role of interferons in activation of early
response genes and antiproliferative responses; and modulation of
signal transduction pathways by pathological events such as malignant
transformation.
- Steven Dowdy
Regulation of G1 cell cycle progression in cancer; consequences of
genetic and epigenetic alterations and activating mechanisms of cell
cycle machinery.
- Jack Dixon
Role of specific phosphatases in cancer and tumor suppression;
ability of the tumor suppressor PTEN, a PTPase, to dephosphorylate
phosphatidylinositol 3,4,5-triphosphate.
- Xiang-Dong Fu
Mechanisms and regulation of pre-mRNA splicing in eukaryotic cells;
deregulation of alternative splicing in cancer; functional studies of the
SR (for serine and arginine-rich) family of non-snRNP splicing factors,
and regulation of SR proteins by phosphorylation.
- William Gerwick
Marine natural product isolation and identification, including the
isolation of antiproliferative agents from marine algae and cyanobacteria;
anticancer drug discovery using mechanism-blind (solid tumor selective
cytotoxins) as well as mechanism-based strategies (epigenetic targets).
- Gouri Ghosh
High-resolution structure studies of protein/nucleic acid complexes
involved in transcription and splicing, including NF-N:B, IN:B, and
IN:B-kinase (IKK); mechanism of NF-N:B dimerization; transcriptional
regulation by NF-N:B; role of serine/arginine rich proteins (SR proteins)
in pre-mRNA processing.
- Partho Ghosh
Mechanisms of growth factor receptor activation; Met (hepatocyte growth
factor receptor, HGFR); Listeria monocytogenes InlB as a mimetic of
hepatocyte growth factor (HGF); inflammation and cancer; regulation of
inflammatory responses.
- Christopher Glass
Nuclear receptors and regulation of gene expression; molecular
crosstalk between nuclear receptors and toll-like receptors; role of
macrophage/cancer cell interactions and nuclear receptor derepression
in the development of hormone resistance.
- Alexander Hoffmann
Importance of NF-N:B regulated signaling networks in cell survival
and proliferation; use of knockout mice for NF-N:B and IN:B genes to
examine NF-N:B signaling networks; cancer-associated roles of NF-N:B
in inflammation, apoptosis and senescence, and potential strategies for
therapeutic intervention.
- Tony Hunter
Tyrosine phosphorylation in regulation of cell cycle and control of cell
proliferation; role of the focal adhesion kinase (FAK) and associated
proteins in cytoskeletal regulation; mammalian cyclins and their role
in cell cycle control.
- Randy Johnson
Hypoxia and hypoxic response via the transcription factors HIF-1 alpha
and c-jun; transgenic studies of angiogenesis involving VEGF responses
to hypoxia; initiation of tumorigenesis by hyperproliferative events in
vivo; mammary function and tumorigenesis.
- Jan Karlseder
Biological functions of mammalian telomeres; telomere dynamics in
premature aging diseases and human cancer; interactions between the DNA
damage machinery and telomeres; telomere processing during the cell cycle;
telomere shortening as an approach to regulate cancer cell growth.
- Richard Kolodner
Mechanisms of genetic recombination and related repair events;
maintenance of genomic stability; identification of genes that prevent
the accumulation of deletion mutations and chromosomal translocations;
genetic functions involved in hereditary non-polyposis colon cancer
(HNPCC).
- Elizabeth Komives
Regulation by protein-protein interactions in signal transduction
including protein kinases and NF-N:B/IN:B interactions, studied by
various methods including proteomics, amide exchange, NMR, surface
plasmon resonance and calorimetry.
- Tadeusz Molinski
Discovery of natural products from marine sponges and cyanobacteria
as leads for antitumor agents; isolation, structure elucidation and
synthesis of compounds with activity in cancer cell models, including
in vivo cell lines; isolation of novel alkaloids with pro-apoptotic and
antitumor properties.
- Cornelis Murre
Function of E2A proteins during lymphocyte differentiation and
development; importance of E47 in programmed cell death during T-cell
lineage differentiation; development of T cell lymphomas resulting from
loss of E2A activity.
- Alexandra Newton
Protein kinase C; signal transduction; membrane biochemistry.
Biochemistry of kinases that transduce lipid signals, particularly
protein kinase C (PKC), the phosphoinositide kinase (PDK-1), and Akt
(protein kinase B); molecular regulation of PKC by phosphorylation and
by interactions with PDK-1; identification of a novel scaffold protein
for PKC.
- Amy Pasquinelli
Role of regulatory RNAs in gene regulation; homologs of let-7 RNA and
its target lin-41 and their role in differentiation; micro RNAs and
their role in human cancer.
- Bing Ren
Development of bioinformatics tools, such as genome wide location analysis
(GWLA), to study in vivo function of transcription factors involved in
tumorigenesis; identification and function of E2F target genes in DNA
damage checkpoint and repair pathways, chromosome segregation, and the
mitotic spindle checkpoint.
- Michael Rosenfeld
Signaling pathways involved in normal and neoplastic development of
neuronal and endocrine systems; molecular regulation of nuclear receptors;
novel co-activators and co-repressors (NCoR) of nuclear receptors; histone
acetyltransferases and deacetylases in ligand-dependent transcriptional
activation.
NOTE: Dr. Rosenfeld
was recently awarded seed money from the UCSD Moores Cancer Center
in the amount of $20,000 for his project entitled
"Molecular Mechanisms Underlying Ewing's Sarcoma:
Roles of Novel Non-coding RNAs."
For more details, click
here.
- Deborah Spector
Regulation of human cytomegalovirus (HCMV) early gene expression by
viral transactivator proteins; control of cell cycle by HCVM infection;
altered transcription, subcellular localization, and stability of key
cell cycle and DNA repair regulatory proteins by HCVM infection; in vivo
pathogenesis of CMV.
- Susan Taylor
Biochemical and biophysical studies of cAMP-dependent protein kinase
(PKA); application of PKA structural/functional information to
entire protein kinase family; control of PKA-mediated signaling by
phosphorylation, myristylation, and interactions with regulatory subunits
and anchoring proteins (AKAPs).
- Roger Tsien
Regulation and role of messengers such as Ca2+, cyclic AMP, and nitric
oxide; engineering of new molecules to detect and manipulate intracellular
biochemical signals; noninvasive imaging of specific mutant versus normal
mRNAs in tumors.
- Judith Varner
Molecular mechanisms regulating tumor angiogenesis; importance of integrin
receptors in tumor angiogenesis; interactions of PKA, the small GTPases
Rho and Rac, and focal adhesion regulatory proteins (FAK and paxillin)
in cell migration and metastasis; interactions of ECM proteins and their
integrin receptors.
- Geoff Wahl
DNA repair and control of DNA replication. Role of chromosome breakage
in gene amplification; strategies to eliminate amplified genes from
cancer cells; maintenance of genome integrity and regulation of cellular
responses to DNA damage by p53; mechanisms of spindle inhibitors to
induce multiple rounds of DNA replication without an intervening mitosis.
- Jean Wang
Control of apoptosis by DNA-damage activated signaling pathway involving
mismatch repair proteins and c-Abl; defects in apoptotic pathways leading
to drug resistance of mismatch repair-deficient tumors; identification
of DNA damage-activated RB dephosphorylation in S-phase cells.
- Matt Weitzman
Interactions between viruses and cellular DNA repair machinery;
virus-mediated transfer of genetic material into target cells;
inactivation of the Mre11-Rad50-NBS1 DNA repair complex during adenovirus
infection.
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