Why It Is Important

The cost of bringing a new drug to market is now estimated to exceed $1 billion, with the timeline for developing a drug and getting it to market approaching 15 years. During the next 4 years, 9 of the top 10 and 18 of the top 20 best-selling drugs in the world will go off patent. A major challenge for the pharmaceutical industry is their lack of tools to identify promising candidates and to separate the winners from the losers early in the development process. Such tools have the potential to substantially reduce the cost to market for new drugs.

Our Approach

The cCRETE team will focus on assays of invasive potential and inflammatory markers which will be accomplished by measuring cell secreted factors in vitro and in vivo, including peroxide, TNF-alpha and matrix metalloproteinases (MMPs).  We propose to develop cell micro-systems where micro-patterned co-cultures of cancer and non-cancer cells will be juxtaposed with arrays of sensing elements for monitoring downstream readouts of cell-drug interactions.  Our group has also applied in vivo imaging to assess therapeutic efficacy and will validate the new assays with in vivo assays of cell invasion and inflammation.

To address this critical need, a team of cancer biologists, social scientists, bioinformatics experts and bio-engineers has been created to develop and validate high throughput bio-marker assays for the effect of new therapeutics on invasive cancers.  In addition, members of the group have developed novel small molecule therapeutics that effectively inhibit key pathways in these cancers; the success of these new therapeutics will require the development of bio-markers.  The important problem to be solved is the creation of high throughput and content rich assays to summarize the impact of therapeutics on cellular functionality.  The “rich” content required to fully characterize the response to therapy must go beyond the quantification of proliferation and apoptosis to evaluate invasive potential, inflammatory markers, markers of “stem-ness”, autophagy, metabolic pathways and senescence.

Impacts & Highlights

• Developed a novel platform for culturing cancer cells and detecting signals secreted by the cells, in collaboration with Genentech and the Revzin Lab
• Demonstrated 50 fold enhancement of drug delivery to an ablated margin in tumor models that span epithelial cancer and highly invasive mesenchymal phenotypes
• Developed molecular ultrasound imaging strategies that will be disseminated and used in a human study of HCC molecular imaging
• Working to develop a system of in vivo ultra-sound mediated nucleic acid targeting endogenous mesenchymal stem cells (MSCs) for accelerated connective tissue repair based on cell secretions of BMPs
• Installed an MRgFUS system in the SVM MRI to be used in the study of substance delivery across blood brain barriers with Stanford University

Team

Katherine Ferrara	Distinguished Professor of Biomedical Engineering
Steven Currall	Professor of Management
Ralph deVere White	Distinguished Professor and Director of Urology
Frederic Gorin	Professor and Chair of Neurology
Bruce Hammock	Distinguished Professor of Entomology & Nematology
Alexander Revzin	Professor of Biomedical Engineering
Anne Knowlton	Professor of Cardiovascular Medicine
Fitz-Roy Curry	Professor Emeritus of Physiology & Membrane Biology
David Segal	Professor of Biochemistry and Molecular Medicine
Rachel Pollard	Associate Professor of Veterinary Medicine: Surgical and Radiological Sciences
William Murphy	Professor of Dermatology
Kent Lloyd	Professor of Surgery
Edward Kim	Assistant Professor of Hematology & Oncology
Alexander Borowsky	Professor of Pathology
Lisa Even	Staff Research Associate of Biomedical Engineering
Josquin Foiret	Postdoc of Biomedical Engineering
Karen Gagnon	Specialist of Biomedical Engineering
Yandong Gao	Postdoc of Biomedical Engineering
Elizabeth Ingham	Staff Research Associate of Biomedical Engineering
Douglas Stephens	Research Engineer of Biomedical Engineering
Clifford Tepper	Associate Researcher of Biochemistry & Molecular Medicine
Chun-Yen Lai	Postdoc of Biomedical Engineering
Zee Malik	Knowlton Lab Investigator of Cardiology
Dong-Sik Shin	Postdoc of Biomedical Engineering
Sarah Tam	Specialist of Biomedical Engineering
Spencer Tumbale	Junior Specialist of Biomedical Engineering
Anthony Valenzuela	Staff Research Associate of Neurology
Guodong Zhang	Postdoc of Pharmacology & Toxicology
Leif Anderson	Graduate Student of Biomedical Engineering
Sean Kodani	Graduate Student of Pharmacology & Toxicology
Dipali Patel	Graduate Student of Biomedical Engineering
Matthew Silverstrini	Graduate Student of Biomedical Engineering
Samantha Tucci	Graduate Student of Biomedical Engineering
Andrew Wong	Graduate Student of Biomedical Engineering

For more information on this program, please contact Christine Parks ceparks@ucdavis.edu.