Chao Family Comprehensive Cancer Center
Message from Dr. Frank L. Meyskens, Director

CANCER
RESEARCH                                  Progress Brings Hope                                              Summer 2010

Welcome Message from the Director

In this issue, we have several celebrations to note. On Tuesday July 27, 2010, Sprague Hall was the site for the grand opening of the Queen of Hearts Foundation Ovarian Cancer Research Laboratory and the Robert R. and Margaret L. Sprague Women’s Cancer Research Center. Over one hundred of our generous donors and friends were on hand to tour the new facilities, meet with investigators and hear senior university officials commend our progress and pledge continued infrastructure and other support for our cancer center. The buildout of the ground floor of Sprague Hall is complete and several research laboratories are already moving in. This is an exciting milestone for us.

A second exciting milestone was the certification of our Division of Hematology/Oncology through the American Society of Clinical Oncology (ASCO) Quality Oncology Practice Initiative (QOPI). This accreditation and certification process assures patients and their families that our oncology practice meets rigorous standards for high-quality cancer care. Ours is among the country’s first, and California’s only, QOPI-certified practice and is the only one in the U.S. that is directly affiliated with a NCI-designated comprehensive cancer center.

Much of this success is due to the dedication and diligence of our outgoing Associate Director for Clinical Research, Dr. Randall Holcombe. Randy is on his way to new challenges at Mount Sinai hospital in New York, where he will assume the positions of Director of Clinical Oncology for their Medical School and Medical Center, head of GI Oncology and Associate Director of their Cancer Institute. Please join me in thanking Dr. H. for his essential contributions and for many years of tireless effort, hard work and devotion to our cancer center. We all will sincerely miss you.

Dr. Hung Fan and his team at the Cancer Research Institute hosted their annual Campuswide Symposium on Basic Cancer Research at Sprague Hall on May 8, 2010. Rising stars Drs. Daniela Bota and Young Jik Kwon gave splendid seminars and the keynote address by Dr. John Rossi was outstanding. It was a great day of science.

Shared Resource Highlight: Optical Biology Core

Website:Optical Biology Core
Contacts: Director: J. Lawrence Marsh, Ph.D.
Facility Manager: Michelle Digman
Finance Manager: Jennifer Walker
Location: 5203 Biological Sciences II, UC Irvine, Irvine, CA 92697

The Optical Biology Core (OBC) provides researchers at UC Irvine and local Universities access to state of the art instrumentation and expertise in advanced in vivo imaging. The OBC houses a Zeiss 510 META NLO 2-photon scanning microscope and a Zeiss 510 META system. In collaboration with the Laboratory for Fluorescence Dynamics (LFD), a Zeiss LSM710 NLO two-photon confocal microscope, an Olympus FV1000 and the Olympus OV110 for small animal imaging are also available at the OBC. They provide workshops, training, consultation, and promote the use of unique imaging technologies to enhance individual research programs. They also optimize and develop instrumentation and keep up to date with the latest cutting edge technologies in confocal imaging.

The OBC directly supports research programs led by several cancer center members. Dr. Edward Nelson is developing novel nanotechnology for molecular profiling of tumor cellular elements. Micropallet arrays are composed of thousands to millions of selectable micorpallets on which cells are positioned. Multilaser excitation, using the LSM710, facilitates cell identification, and the high sensitivity essentially eliminates degradation of samples. Dr. Christine Suetterlin has identified a novel regulatory pathway that controls the organization and function of the centrosome. These studies rely on the LSM710 for fluorescence correlative spectroscopy to identify the flow of molecules from the membrane to the centrosome. Dr. Wen-Hwa Lee studies Hec-1, a prognostic marker for poor clinical outcome of breast cancers. The OBC equipment and facilities are essential tools for extended time-course studies and 3D reconstructions. Dr. Dave Fruman’s studies of TORC1/2 kinase inhibitors in leukemia cells, which were published earlier this year in Nature Medicine, relied on the multi-laser excitation for four-color fluorescence images.

Recent high impact publications

Dr. Ellis Levin and colleagues: ‘Heat shock protein 27 is required for sex steroid receptor trafficking to and functioning at the plasma membrane’, Mol Cell Biol 30, 3249-3261. Levin’s group has found that estrogen receptors and androgen receptors perform signalling functions at the cell membrane, in addition to their acknowledged roles as nuclear transcription factors. This paper used proteomics and mutational analyses to demonstrate the requirement for interaction with HSP27 for proper membrane localization. The implications of ER and AR at the cell membrane for breast and prostate cancer and for development of novel therapeutics are not yet fully known.

Dr. Anand Ganesan and colleagues: ‘Protein interaction network topology uncovers melanogenesis regulatory network components within functional genomics datasets’, BMC Systems Biology 4, 84-96. Dr. Ganesan has performed several RNAi-based functional genomics screens to uncover key components that regulate both normal pigmentation and melanomagenesis. This paper describes a novel protein-protein interaction topology network approach to target identification. The apporach identified novel components of well-characterized biological pathways from functional genomics datasets that could not have been identified by existing statistical and computational approaches.

Congratulations to the following cancer center members:

Dr. Young Jik Kwon received a National Sciences Foundation CAREER award worth $374,467 (direct costs) , to develop ‘Acid-Transforming Polypeptides as Stimuli-responsive, Efficient, Biocompatible, and Tunable Nonviral Gene Carriers’. The Faculty Early Career Development (CAREER) Program is a Foundation-wide activity that offers the National Science Foundation's most prestigious awards in support of the early career-development activities of those teacher-scholars who most effectively integrate research and education within the context of the mission of their organization. Such activities should build a firm foundation for a lifetime of integrated contributions to research and education.

Dr. Marian Waterman was awarded a $1,277,101 grant from the California Institute for Regenerative Medicine to study ‘TCF-3: A Wnt Pathway Effector and Nanog Regulator in Pluripotent Stem Cell Self-Renewal’. The Wnt pathway is central to the progression of several tumor types, and to the control of lineage specific differentiation of human embryonic stem cells as well as induced pluripotent cells.

Dr. Michael Cahalan has been elected to the National Academy of Sciences (NAS). Election to the prestigious NAS is one of the highest honors awarded to US scientists. His pioneering research on signaling molecules in T cells has identified promising therapeutic targets for treatment of autoimmune disorders, as well as being applicable to cancer. He is using two-photon microscopy to visualize the dynamics of immune cells as they interact in real time during immune responses. His group’s finding that inflammatory and autoimmune responses can be blocked while allowing normal immune system responses to fight off viral and bacterial infections also has applications in cancer treatment.

Upcoming Cancer Center events

We are looking forward to seeing you at the Annual Scientific Retreat, November 12-13, 2010, in Palm Springs! We also want to thank you in advance for your assistance and engagement as we work toward submission of the CCSG non-competing renewal, which is due at the end of November.

Editor’s corner

To continue with my past train of thought regarding science policy and NCI funding, I thought it would be interesting to compare and contrast the $6 billion NCI research budget to some numbers* from the biotechnology industry.

Three companies, Genentech, Celgene and Biogen Idec, together spent $5 billion on Research & Development in 2008. Their combined revenues were close to $20 billion. Genomic Health (makers of Oncotype Dx) earned $111 and 150 million in 2008 and 2009, respectively, while spending $29 and $36 million on R&D. Dendreon (Provenge) earned only $100,000 each year, but spent $50 and $60 million on R&D. Smaller companies Cell Therapeutics (Pixantrone) and Gen Vec (TNFerade) are spending $20 to 70 million per year on R&D with revenues less than $15 million.

A $6 billion budget, divided ONLY amongst the 60 NCI-designated cancer centers ($100 million each) would be only slightly more than the R&D spending of 2 average biotech companies per cancer center. And of course, the NCI funds are distributed not only to cancer centers. Total current NCI plus all NIH funding to our cancer center members is $55 million per year. So our cancer center members operate with a budget from NIH funding that is equivalent to the R&D spend at a mid-sized biotech. With a $6 billion budget, how much cancer research would be accomplished in biotech?

Comments and suggestions for future news items to Randy Berg (rberg@uci.edu)

*Data from http://finance.yahoo.com

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