UC Davis Cancer Center

Scientific accomplishments  
 

Molecular oncology program

$12.43 million in current research funding

65 ongoing research projects  
 

Research highlights and major accomplishments 2002-2005

• Developed and applied nano-technology to study protein-DNA interactions at single molecule resolution (Balhorn, Kowalczykowski, Nature 2001, Cell 2003)
• Discovered mechanism of negative regulation of Rad51 filament by Srs2 helicase (Kowalczykowski, Nature 2003)
• Discovered first bi-polar DNA helicase (Kowalczykowski, Nature 2003)
• Studied mechanism of Rad54 ATPase in recombination (Heyer, Molecular Cell 2003; Kowalczykowski, Nature Structural Biology 2003)
• Studied function of kinesins in chromosome segregation (Scholey, Nature 2004)
• Studied role of APC in chromosome segregation (Kaplan, Nature Cell Biology 2001, The Journal of Cell Biology 2004)
• Explored mechanisms of crossover control (Hunter, Cell 2004; Kowalczykowski, Cell 2004)
• Investigated mechanism of RecFOR in RecA-mediated recombination (Kowalczykowski, Molecular Cell 2003)
• Studied regulation and signal diversification of erbB/EGFR family kinases (Carraway and Sweeney, Cancer Cell 2002, Molecular Cell Biology 2003)
• Studied role of Etk tyrosine kinase in cell migration and androgen independence (Kung, Nature Cell Biology 2001, Molecular Cell Biology 2002)
• Investigated regulation and function of coactivator ACTR in androgen receptor signaling (Chen, Science 2003; Chen and Kung, Proceedings of the National Academy of Sciences 2003)
• Studied regulation of PML and PML-RAR by arsenic trioxide via MAP kinase  (Privalsky, Cancer Cell 2004, Molecular and Cellular Biology 2003)
• Developed a novel approach to identifying oncogene myc and E2F target genes (Farnham, Genes & Development 2003, Proceedings of the National Academy of Sciences 2003)
• Discovered a novel NAD-dependent signal pathway in cell survival (Lin SJ, Genes & Development 2004, Nature 2002)
• Discovered a novel cofactor for DNA methylase (Chedin, Proceedings of the National Academy of Sciences 2004)
• Established an in vitro system for mitochondrial fusion (Nunnari, Science 2004)

Cancer biology in animals program

$9.14 million in current research funding

41 ongoing research projects  
 

Research highlights and major accomplishments 2002-2005

• Characterized the PyV-mT models systems of mammary tumor development and progression (Galvez, Comparative Medicine 2004; Namba, Molecular Cancer Therapeutics 2004; Maglione, Breast Cancer Research 2004)
• Characterized the Nkx3.1/Pten model of prostatic neoplasia (Shapell, Cancer Research 2004; Abate-Shen, Cancer Research 2003; Park, The American Journal of Pathology 2002; Kim, Proceedings of the National Academy of Sciences 2002, Cancer Research 2002)
• Evaluated the roles of galectin-3 and galectin-7 in tumor biology (Ueda, Cancer Research 2003; Hoyer, The American Journal of Pathology 2004; Kopitz, Oncogene 2003; Sano, The Journal of Clinical Investigation 2003; Kuwabara, The Journal of Biological Chemistry 2002)
• Analyzed the role of c-Jun in tumorigenesis (Li, Developmental Cell 2003; Sprowles, Oncogene 2003; Palmada, The Journal of Cell Biology 2002)
• Used novel imaging technologies to follow tumor progression noninvasively in vivo (Abbey, Proceedings of the National Academy of Sciences 2004; Pollard, Investigative Radiology 2004; Chomas, Radiology 2003)
• Analyzed the molecular mechanisms behind herpes virus-induced malignant transformation (Montaner, Blood 2004; Sodhi, Proceedings of the National Academy of Sciences 2004; Lupiani, Proceedings of the National Academy of Sciences 2004; Hamza, Journal of Biological Chemistry 2004; Cui, Journal of Virology 2004; Chang, Journal of Virology 2004; Liao, Journal of Virology 2003; Montaner, Cancer Cell 2003; Izumiya, Journal of Virology 2003; Levy, Journal of Virology 2003; Penfold, Journal of Virology 2003; King, Veterinary Microbiology 2002)
• Characterized kinase dysfunction in spontaneous canine cancers (Shelly, submitted to Mammalian Genome; Zadovaskaya, Journal of Veterinary Internal Medicine 2004; Jones, Journal of Veterinary Diagnostic Investigation 2004; Downing, American Journal of Veterinary Research 2002)
• Conducted clinical trials of novel therapeutics and diagnostics in companion animals with cancer (Kent, Journal of Trace Elements in Experimental Medicine 2004; Pryer, Clinical Cancer Research 2003; London, Clinical Cancer Research 2003; Wisner, Investigative Radiology 2003; Liao, Blood 2002)
• Developed whole slide imaging technology [This technique captures the entire glass slide at 50,000 dpi and processes the image so that it can be displayed over the Internet. See: http://imagearchive.compmed.ucdavis.edu/]

Cancer therapeutics program

$13.82 million in current research funding

89 ongoing research projects  
 

Research highlights and major accomplishments 2002-2005

• Developed and reported three different novel Chemical encoding methods for small molecule and oligomeric “one-bead, one-compound” combinatorial libraries (Journal of the American Chemical Society 1992, 1993, 1994, patent pending)
• Reported a novel and highly versatile Chemical microarray method for proteomics research and for the development of diagnostics (Molecular Diversity 2004, patent pending)
• Reported the use of accelerated mass spectrometer (LLNL), in conjunction with protein sequencer, to determine the amino acid sequence of 14C-labeled protein at attomole sensitivity (Proceedings of the National Academy of Sciences 2001)
• Identified novel ovarian cancer glyco-markers with mass spectroscopy (patent pending)
• Developed effective 67Cu-chelation and novel chelate linkers for radioimmunotherapy (Clinical Cancer Research 2003)
• Discovered and developed preclinical data supporting a novel anti-CD-22 monoclonal antibody that has lymphomacidal properties in xenograft models (Blood 2003), leading to an NCI RAID award for humanization and formulation and pending clinical trials
• Developed and patented a novel library screening method to identify synthetic ligands that bind to cancer cell surface receptor (US Patent #6,670,142 B2, Dec. 30, 2003)
• Established a role for p21 in the suppression of apoptosis in breast cancer cells (Molecular Cancer Therapeutics 2003)
• Showed that galectin-3 inhibits apoptosis of tumor cells, possibly through interactions with Bcl-2, and that inhibitors against this protein may be therapeutic (Nature Reviews. Cancer 2004)
• Completed the first clinical trial of a multi-targeted kinase inhibitor in dogs with cancer that served as the basis for a Phase 1 human clinical trial of a similar Drug (Clinical Cancer Research 2003)
• Identified markers of tumor hypoxia as predictive factors for clinical benefit from the hypoxic cytotoxin tirapazamine and the anti-angiogenic agent SU5416 (Clinical Cancer Research 2003)
• Identified in vitro mechanisms of action of the cell cycle modulatory agent 7-OH staurosporine and provided new insights into the role of UCN-01 in abrogating the G2-M checkpoint following administration of DNA-damaging chemotherapy (Cancer Chemotherapy and Pharmacology 2003)
• Identified free tumor DNA in plasma as a predictive factor for patient outcome in clinical trials (Annals of the New York Academy of Sciences 2004)
• Established clinical and molecular predictors of survival in bronchioloalveolar cancer patients treated with the EGFR inhibitor gefitinib (Clinical Cancer Research 2004)

Cancer etiology, control and prevention program

$12.55 million in current research funding

51 ongoing research projects  
 

Scientific accomplishments 2002-2005

• Studied role of CYP2B, CYP2E, CYP2F and CYP4B in bioactivation of lung toxicants (Buckpitt and Plopper, Epidemiology 2002)
• Studied ozone-induced changes in glutathione in lung subcompartments of rats and monkeys (Plopper, Buckpitt and Wu, Toxicology and Applied Pharmacology 2003
• Explored metabolism of naphthalene and 1-nitronaphthalene in dissected airways (Buckpitt and Plopper, The Journal of Pharmacology and Experimental Therapeutics 2004, Drug Metabolism Reviews 2002)
• Described X-ray crystal structure for human epocide hydrolase (Hammock, Biochemistry 2004)
• Developed assays for cypermethrin, an environmental pesticide in water, and for pyrethrene and its metabolites in human urine (Hammock, Journal of Agriculture and Food Chemistry 2004, Chemical Research in Toxicology 2004)
• Studied the impact of soot and iron particles on biological responses in the lung of rats (Pinkerton, Pharmacology 2003, Environmental Health Perspectives 2003)
• Advanced understanding of the mechanism of TCDD-induced carcinogenesis  (Monk, Denison and Rice, Environmental Toxicology and Chemistry 2002, Marine Pollution Bulletin 2002)
• Developed assay for atmospheric oxidants (Burtis, Genetics 2004)
• Developed cancer risk estimates for Juarez, Mexico, based on study of Ah receptor-mediated activity from air particulates at the U.S.-Mexico border (Denison, Environmental Health Perspectives 2003)
• Examined individual variation of pyrethroid-selective esterases in human liver (Hammock, Analytical Biochemistry 2003)
• Studied impact on human mortality of environmental pollutants including dioxin, metals and diesel fumes (Hertz-Picciotto, Scandinavian Journal of Work, Environment & Health 2003)
• Found increased respiratory disease and potential endocrine disrupters (PCSs) associated with home heating with coal in the Czech Republic (Hertz-Picciotto, Environmental Health Perspectives 2003)
• Showed that African American males are consuming more carcinogenic heterocyclic amines than other U.S. racial or ethnic groups (Bogen, Journal of Chromatography B: Biomedical Sciences and Applications 2004)
• Discovered that human pet foods have carcinogenic heterocyclic amines (Knize, Mutation Research 2003)
• Showed that a number of foods, especially high-fiber ones, lowered the soluble heterocyclic amines available for adsorption into the blood, thus lowering the internal dose of the carcinogens (Kulp, Food and Chemical Toxicology 2003)
• Showed for the first time that the carcinogen PhIP, present in cooked meat, causes DNA changes in the human colon (Dingley, Proceedings of the American Association for Cancer Research 2004)
• Investigated the association of heterocyclic amines and meat intake with colon cancer in a population-based study (Butler, American Journal of Epidemiology 2003)
• Screened extracts of 22 dietary herbal supplements and 21 food products for cancer chemoprevention properties (Denison, Journal of Agricultural and Food Chemistry 2003)
• Studied anti-tumor and immune-enhancements properties of mushroom extract (Keen, Experimental Biology and Medicine 2004)
• Showed that mice smoking for just one month had much higher metastasis of injected breast tumor cells in the lung (Pinkerton and Erickson, Chest 2004)
• Reported that tobacco is the single most important reason for the excess cancer burden among African American men (Leistikow, Preventive Medicine, 2004)

Prostate cancer program

$4.29 million in current research funding

32 ongoing research projects  
 

Major programmatic and scientific accomplishments 2001-2004

• 15 newly funded peer-reviewed prostate cancer grants, four additional applications recommended for funding
• 11 clinical trials accruing prostate cancer patients
• Developed a functional assay for quantitating wild-type and mutant androgen receptor activities, and molecular alterations in progression to androgen independence (Cancer Research 2002, Prostate 2004)
• Established that p53 gain-of-function mutant alleles participate in the androgen-independent growth of prostate cancer (Cancer Research 2002, Prostate 2002)
• Defined the effects of nutritional supplements on DNA adducts, prostate cancer cells and in patients (Nutrition and Cancer 2003)
• Explored lycopene-induced G1 arrest and cyclin D down regulation in prostate cells (Journal of Nutrition 2003)
• Explored enhancement of radiation treatment for prostate cancer due to modulation of Bc12 and p53 (Cancer Research 2003, Cancer Biotherapy and Radiopharmaceuticals 2002, International Journal of Radiation Oncology, Biology, Physics 2003)
• Identified CTEN, a potential tumor-suppressor gene in prostate cancer (Cancer Research 2002)
• Identified LRIG1, a negative regulator of the HER family of receptors (2004, in press 2004)
• Described IL-8 activation of the androgen receptor through non-receptor tyrosine kinases (Oncogene 2004)
• Developed a new neuroendocrine mouse model of prostate cancer using gastrin-releasing peptide (GRP)
• Conducted pre-clinical studies that have led to investigator-initiated clinical trials in prostate cancer patients, including inhibition of prostate cancer growth by genistein and intermittent dosing of chemotherapy with either molecularly targeted proteasome or EGFR inhibitors (Urology 2004)
• Performed correlative science studies using the Clinical and Molecular Pharmacology Shared Resource, including one demonstrating the significant associations of N-telopeptide levels with overall survival, and osteocalcin levels with progression-free survival, in prostate cancer patients treated with a matrix metalloproteinase inhibitor.

Biomedical technology program

$8.1 million in current research funding

26 ongoing research projects  
 

Scientific accomplishments 2002-2005

• Developed a breast CT machine that may be more accurate than mammography, without requiring breast compression (Radiology 2001)
• Developed a new technology for spectroscopic imaging of bladder cancer by cystoscopy (Journal of Biomedical Optics, 2004A, Journal of Biomedical Optics, 2004B)
• Began work on a custom CT/PET system for breast imaging
• Developed bioaerosol mass spectrometry for the possible detection of lung and bladder cancer
• Began work on a project to improve diagnosis in clinical PET/CT by motion compensation
• Developed synthetic high affinity ligands (SHALs), and began exploring potential applications in cancer therapeutics and diagnostics (Chemical Research in Toxicology 2002)
• Developed ultra-sensitive quantitation of heterocyclic amine adducts using accelerator mass spectrometry (Molecular and Cellular Proteomics 2002)
• Explored bone metastasis biomarker for cancer detection and staging
• Developed and have begun evaluating technique for noninvasive characterization of hematopoietic cancer cells by Raman spectroscopy (Annals of Chemistry 2004)
• Began work on contrast-enhanced dual energy mammography (Radiology 2002)
• Completed initial work on a compact accelerator for proton therapy
• Researched multimodal methods of tissue ablation
• Worked toward development of high spatial/temporal resolution pharmacokinetics and pharmacodynamics of cancer therapeutics
• Began developing technology to enable image-guided surgery at the cellular level
• Developed novel short interfering hybrids DNA: RNA molecules (siHybrids) for gene silencing
• Demonstrated feasibility of integrated PET and CT imaging in the mouse (Physics in Medicine and Biology 2002)
• Designed a MINX system for small-animal imaging that could lead to a 200-400 reduction in radiation dose to the animal, compared to micro-CT
• Made advances in contrast-enhanced ultrasound imaging and Drug delivery
• Developed the feasibility of high-field gradient insulators which can enable the development of a very compact proton radiotherapy accelerator tube while still achieving the necessary particle (proton) energies to provide efficacious radiotherapy
• Developed hyperspectral microscopy for cancer detection at the microscopic level
• Developed quantitative evaluation of peripheral tumor perfusion and permeability using contrast-enhanced CT