TAG: "Translational medicine"

UCSF moves ahead with plans for new General Hospital research facility

SFGH building would support long-standing partnership, catalyze research progress.

In addition to being the city's safety-net hospital and a premier trauma center, San Francisco General Hospital is home to breakthrough research by UCSF scientists. (Photo by Steve Babuljak)

By Kate Vidinsky, UC San Francisco

It has been more than a decade since a baby was born HIV-positive in San Francisco.

This is no small feat, considering transmission of the disease from untreated HIV-positive mothers to their children used to occur in one of every four cases.

Thanks in large part to groundbreaking research from the unique partnership between UC San Francisco and San Francisco General Hospital and Trauma Center (SFGH), researchers are now focused on finding a cure for HIV, a disease that first emerged as an almost certain death sentence.

“The roots of the remarkable progress in HIV medicine over the last three decades can be traced to the partnership between UCSF and SFGH,” said Diane Havlir, M.D., a UCSF professor of medicine and chief of the HIV/AIDS Division at SFGH.

“Thanks to these efforts, we are now talking about curing HIV and aging in HIV – topics we never imagined, even a decade ago.”

The newly constructed San Francisco General Hospital and Trauma Center will open in 2015, providing an updated place to treat the city’s population. In line with these efforts to renew and refresh the SFGH campus, UCSF is hoping to to construct a new UCSF research building at SFGH.

The building would provide modern research facilities, centralize the research efforts that are currently spread throughout nine buildings at SFGH, and allow UCSF to comply with University of California seismic policies. It would house many research centers, affiliated programs and major labs that are dedicated to improving the health of the SFGH patient population and individuals worldwide.

“Our HIV researchers are recognized internationally for their collaborative approach, community involvement and close ties to the San Francisco Department of Public Health,” Havlir said. “A new UCSF research building at SFGH will bring together teams from different disciplines under one roof and undoubtedly catalyze progress for all its tenants.”

Historic partnership

The mutually beneficial partnership dates back to 1864, when Toland Medical College opened across the street from San Francisco’s county hospital to provide clinical training for doctors serving the citizens of the booming Gold Rush city.

For more than 140 years, the offspring of those two entities – UCSF and SFGH – have worked together to provide the best care for some of the city’s most vulnerable patients. Long recognized as San Francisco’s public safety-net hospital, SFGH provides primary, specialty and hospital care to everyone in San Francisco, regardless of their ability to pay.

The hospital also is home to the city’s only trauma center.

Nearly 2,000 UCSF physicians and staff work side-by-side at SFGH with 3,500 employees of the San Francisco Department of Public Health.

In addition to being an essential training site for UCSF physician residents, SFGH is a major research site for UCSF. The hospital receives about $150 million in research grants each year, which accounts for a quarter of all National Institutes of Health grants awarded to UCSF.

“Many of our clinicians are physician-scientists and do research dedicated to the needs of our patients. Their discoveries improve the health of our city and impact health worldwide,” said Sue Carlisle, Ph.D., M.D., vice dean of the UCSF School of Medicine.

Applying the research to benefit patients

Each year, more than 4,000 cases are treated in the SFGH Level 1 trauma center. Of those, about 1,100 involve some sort of musculoskeletal injury – usually resulting from car or motorcycle accidents, or a fall – and more than 200 are admitted for orthopedic surgery.

According to Theodore Miclau, M.D., chief of orthopaedic surgery at SFGH, research informs every aspect of his clinical practice.

“We incorporate a research component into everything we do and focus on translational problems that directly benefit our own patients, while paving the way internationally,” he said.

Miclau’s team has adopted a true bench-to-bedside approach that encompasses every aspect of orthopaedic research – from molecular biology and biomechanics lab work to traditional clinical and procedure-based studies. By examining how bones heal at the molecular and cellular levels, UCSF experts are developing new therapeutic strategies to make bones heal faster and then offering those therapies to patients at the hospital.

Building for the future

UCSF’s research programs at SFGH are currently housed in several buildings at SFGH, including the historic brick buildings that line Potrero Avenue.

These buildings no longer meet UC’s seismic safety standards and UCSF’s research operations must be relocated by October 2019.

The proposed site for the new research building is the parking lot adjacent to 23rd Street. Approximately 800 UCSF employees will work in the new building, including 200 UCSF physician-scientists and clinicians.

Earlier this month, San Francisco’s Health Commission unanimously approved a resolution supporting the first step in the approval process – a non-binding term sheet. The Board of Supervisors will consider the proposal in June.

Following approval by the San Francisco Board of Supervisors and the UC Board of Regents, UCSF will complete an environmental impact review (EIR). After completion of the EIR, it is anticipated that negotiations on the ground lease will be finalized and approvals sought by the Board of Supervisors and Board of Regents in spring/summer 2016.

“What makes our work successful isn’t the individual or the place. It’s the team,” Miclau said. “Having a new research building is critical because it keeps researchers and surgeons co-located. The ability to easily collaborate with others will help translate our findings in truly meaningful ways for our patients, which in the end is what we all ultimately strive for.”

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Drug, Device, Discovery and Development initiative moves forward

UC collaborative aims to speed the discovery, development of products that improve health.

By Carole Gan, UC Davis

On April 15, more than 40 scientists from across the University of California system and representatives from the biomedical industry met to discuss plans for strengthening UC’s position in drug, device and diagnostics development.

The meeting was part of the Drug, Device, Discovery and Development (D4) initiative, a collaborative effort among UC’s five medical campuses to pool resources and expertise to accelerate the discovery and development of products that improve health.

The full day event, held in San Francisco, consisted of panel discussions and breakout sessions, with the ultimate goal of creating an efficient model for multicampus collaborations with industry partners and setting up a UC Drug Discovery Alliance. D4 has been working in tandem with the University of California Biomedical Research Acceleration, Integration & Development (UC BRAID) program to define D4’s priorities.

“We have come a long way since the inception of D4 two years ago and are now in the position to take tangible steps forward on these priorities,” said June Lee, professor of medicine and director of early translational research at UCSF. “By bringing diverse stakeholders from all of our medical campuses together with leaders from the UC Office of the President and external stakeholders, we will be able to put together and execute on an informed plan.”

Michael Rogawski, professor of neurology, leads the D4 initiative for UC Davis. Other UC Davis representatives included Dushyant Pathak, associate vice chancellor for technology management and corporate relations, and Ahmad Hakim-Elahi, executive director for research administration and director of sponsored programs.

“The opportunities that we are addressing will greatly enhance translational research across the UC system and ensure that researchers’ promising discoveries achieve their potential for clinical impact,” Rogawski said. “All of our campuses have great science and unique strengths to offer, and working together, we will have an even more profound impact on the future of drugs, devices and diagnostics.”

Connecting with industry, stimulating drug discovery

The first panel addressed how to set up a successful collaboration between several UC institutions and an industry partner and featured representatives from UCSF, UC Irvine, UC Davis, MedImmune and Quest Diagnostics.

A number of topics generated robust discussions, including how to create a mechanism for connecting industry with academic researchers, streamlining the contracting process and managing complex collaborative projects. UC BRAID already has commenced work on multicampus agreements in the realm of clinical trials, and several suggestions were explored that would allow for the comparative advantages of each BRAID campus to be more readily apparent to the biopharmaceutical industry.

The second panel discussed enabling and stimulating early drug discovery in academia and debated models for the creation of the UC Drug Discovery Alliance. Representatives from UCSF, Gladstone Institutes, Takeda Pharmaceuticals, MedImmune and the National Institutes of Health participated.

Pharmaceutical companies are increasingly looking to academic institutions to supply de-risked drug targets and candidates. However, the challenges for an academic researcher to move from basic disease-related research to the identification and development of a drug candidate are immense. The UC Drug Discovery Alliance will support UC researchers by supplying expertise in drug development, access to UC core facilities and pilot funding, and will enable the translation of many more novel therapeutics projects from the lab to patients. The creation of quality data and robust intellectual property packages for projects  also will create significant value for the UC system.

The panel identified the need for institutional support, diverse sources of funding and partnerships within the life-science ecosystem as key areas of focus. There also was lively debate around the type of organizational model the UC Drug Discovery Alliance would adopt and how to engage industry partners.

Following the panel discussions, multiple breakout sessions were held to identify high priority action items and lay out next steps. Multicampus, cross-functional workgroups will now begin work to move specific initiatives forward. Next steps for the UC Drug Discovery Alliance include selecting a focus area, initiation of partnering and fundraising activities, and creating a business plan.

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Calico licenses technology from UCSF laboratory

Project seeks to develop potential therapies for cognitive decline.

Calico, a company whose mission is to harness advanced technologies to increase understanding of the biology that controls human lifespan, and UC San Francisco have partnered on an innovative project to develop potential therapies for cognitive decline.

Under the agreement, Calico will receive an exclusive license to technology discovered in the laboratory of Peter Walter, professor of biochemistry and biophysics at UCSF. Walter is an investigator in the Howard Hughes Medical Institute, member of the U.S. National Academy of Sciences and recipient of the prestigious Albert Lasker Basic Medical Research Award in 2014.

The agreement is focused on modulators of the integrated stress response (ISR), a set of processes activated in cells under conditions of stress. Under some circumstances, the ISR can be deleterious. For example, under certain circumstances the ISR may contribute to memory decline, a significant problem potentially addressed by the licensed technology.

“We are delighted to enter into this agreement with UCSF and we are excited to translate these research findings into potential treatments for age-related cognitive disorders,” commented Hal Barron, Calico’s president of research and development. “Peter is a world-class basic scientist whose insights have fundamentally changed our understanding of how cells function under stress.”

The work conducted in the Walter laboratory was led by Carmela Sidrauski, a former UCSF researcher and now a scientist at Calico.

“Calico will be a great partner to explore the promise of our research,” Walter said. “Their commitment includes conducting key additional research, hiring outstanding investigators like Carmela and providing critical development expertise.”

Under the terms of the agreement, UCSF will receive an undisclosed up-front fee, and potential milestone and royalty payments. Calico will take responsibility for further research, development and commercialization of resulting therapeutics.

This partnership was facilitated by the UCSF Office of Innovation, Technology & Alliances (ITA), which coordinates UCSF’s efforts in forging collaborations and licensing technologies that translate cutting-edge science on campus into therapies and products that directly benefit patients worldwide.

Calico (Calico Life Sciences LLC) is a Google-founded research and development company whose mission is to harness advanced technologies to increase our understanding of the biology that controls lifespan. Calico will use that knowledge to devise interventions that enable people to lead longer and healthier lives.

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Taking up the tricorder challenge in the spirit of ‘Bones’

UC San Diego professor heads Qualcomm Tricorder XPRIZE physician oversight team.

By Patti Wieser, UC San Diego

Working on the Qualcomm Tricorder XPRIZE is, well, a bit infectious.

“’Star Trek’ is one of the things that tugs on the heart strings of many around the world and I’m not immune to that,” said Gene “Rusty” Kallenberg, M.D., professor and vice chair, Department of Family Medicine and Public Health at the UC San Diego School of Medicine.

Kallenberg is leading the physician oversight team for the Qualcomm Tricorder XPRIZE for which the UC San Diego Clinical and Translational Research Institute (CTRI) has been selected as the testing site. Inspired by the medical tricorder in the “Star Trek TV series and movies, the Qualcomm Tricorder XPRIZE is a global competition sponsored by the Qualcomm Foundation to develop a consumer-friendly, mobile device capable of diagnosing and interpreting 15 physiological conditions and capturing vital health metrics. Ten teams from six different countries have been selected as finalists. As part of the final testing round, teams will compete in both diagnostic experience evaluations and consumer testing, beginning this summer. The final judging and awards ceremony will then take place in early 2016 to coincide with the 50th anniversary of the Star Trek TV show.

“We are very excited to partner with UC San Diego on this important stage of the competition,” said Grant Campany, senior director, Qualcomm Tricorder XPRIZE. “Our finalist teams are developing real medical Tricorder devices that must diagnose 15 medical conditions and capture five vital signs, but the submissions must also be packaged in a consumer-friendly manner. Therefore, this final testing phase is critical in seeing how consumer testers recruited by UC San Diego respond to the overall experience.”

In his Qualcomm Tricorder XPRIZE role, Kallenberg is enlisting the support of physicians in the recruitment of consumer testers for the experimental devices. To help him, he assembled a physician oversight team, made up of UC San Diego physicians Dustin Lillie, Benjamin Johnson and Amy Leu. Consumer testers are volunteers with one or more of the 15 conditions who will test the devices and provide feedback via surveys. Kallenberg is confident the project will attract physicians and consumer testers alike.

Empower patients

“It’s intriguing, intellectually challenging and very much on the cutting edge of health care technology for enabling self-assessment, self-diagnosis and self-monitoring,” Kallenberg said. “A tricorder could empower patients.”

The physician oversight team first had to ensure there was enough epidemiological data to support the ability to find an adequate number of consumer testers.

“Having enough people is the biggest challenge,” Kallenberg said. “Cases for acute conditions such as pneumonia will come from day-to-day acute care settings and our primary care and emergency medicine colleagues; those for chronic conditions such as diabetes and atrial fibrillation will come from patient databases; and rarer conditions such as melanoma and tuberculosis will come from either specialty colleagues/clinics or county health departments.”

The team also is addressing the work flow associated with testing.

“How do you talk to potential testers, how do you gauge their willingness to help, and how do you logistically and mechanically carry out the testing?” Kallenberg asked.

His team is developing steps for orienting testers to the particular device they will use, having them use it, and enabling them to assess the user friendliness and experience of each. The project, while not actually a research study, has Institutional Review Board (IRB) approval in its capacity for oversight on patient privacy rules for the consumer testers. The testers, who are not research subjects, will be informed they are using prototypes.

The physician oversight team also will be in charge of monitoring any medical emergencies and fielding questions during the testing.

“This is a test of the devices’ ability to detect conditions which we already know testers have by virtue of other gold standard tests used in clinical practice,” said Kallenberg. “They will be testing a specific device to see if it can detect their condition.”

Some tests will take about an hour; others will require longer periods.

Kallenberg became involved in the project more than a year ago at the request of Erik Viirre, M.D., Ph.D., the medical and technical director for the Qualcomm Tricorder XPRIZE and an adjunct professor in the departments of neurosciences, surgery and cognitive science at UC San Diego. Viirre believed Epic, UC San Diego Health System’s electronic medical record system, would be an obvious way to identify patients as potential consumer testers, and asked Kallenberg if he would oversee the testing process.

“One thing about academic medicine is you get approached about interesting projects all the time and the other thing about academic medicine is you often say ‘yes,’” said Kallenberg with a grin. “I thought this project was intriguing from the start. Once the oversight team came together and we got into the project, it became infectiously fascinating.”

From house calls to high-tech tricorders

Kallenberg hails from a family of physicians. As a youngster, he often accompanied his father, a GP, on house calls in Cincinnati’s underserved Over the Rhine district, to poor suburban homes with pot-bellied stoves and dirt floors, and to nursing facilities. Kallenberg described his dad as “very much old-style general practice medicine.” Kallenberg also had “bunches of uncles who were physicians and surgeons so medicine was pretty much in the blood,” he said. Contemporary relatives with medical connections include Kallenberg’s wife and his brother, both physicians; his sister, a nurse/counselor; and in-laws, nieces and nephews who have direct or indirect links to medicine. Along his path — from growing up in Ohio to receiving a medical degree at the University of Cincinnati College of Medicine and completing his internship and fellowship training at Harbor-UCLA County Medical Center, to caring for patients, teaching medical students and supporting an integrative medicine approach — Kallenberg has marveled at medical and technological advancements that improve the lives of humans.

Star Trek: The Next Generation made him a true Trekkie, but since the beginning, the show has sparked his interest in medical technology and created an abiding interest in the medical staff of Starfleet starships. “I’ve always kept an eye on the physicians in ‘Star Trek,’” he said. “I use Bones (McCoy), Beverly Crusher and Voyager’s Emergency Medical Hologram duty officer as examples of primary care physicians when talking to medical students.”

He lauded the philosophy of Star Trek” and described creator Gene Roddenberry as a “genius” who tapped into what was truly essential about mankind. “The wonderful thing about ‘Star Trek is that it exemplified what humanity could be and hopefully will become,” Kallenberg said. “The series had human, philosophical stories about life, with ethical challenges and conundrums, and wonderful adventures, and they had the timeline for achieving that enlightened state about right, too — the 2400s!”

For Kallenberg and his team, the Qualcomm Tricorder XPRIZE is a Star Trek-inspired adventure that just may move the tricorder from science fiction to science reality.

“Wired health care is the next step, and the Qualcomm Tricorder XPRIZE is part of that future,” Kallenberg said.

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Quest to create a real-world tricorder

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UC complex contraception registry established to enhance family planning

UC collaborative taps into cross-campus searchable database to help improve patient care.

“You can have a big impact in a woman's life if you are able to identify that she has a need for more contraceptive counseling.” – Sheila Mody, UC San Diego

By Patti Wieser, UC San Diego

With support from the UC Office of the President, the family planning fellowship-trained specialists at the five UC medical center campuses – led by Sheila Mody, M.D., at UC San Diego – have established a UC-wide complex contraception registry.

“We are looking at how women with medical conditions access family planning specialists for contraception and how they make contraceptive decisions,” said Mody, the first family planning specialist at UC San Diego.

Last summer the Complex Contraception Registry–UC Family Planning Collaborative Study began recruiting patients with medical conditions such as diabetes, cardiovascular disease, epilepsy, migraines, cancer and organ transplants. Currently, 75 participants are enrolled in the registry, which is on ClinicalTrials.gov, a service of the National Institutes of Health. The registry contains demographics, diagnoses and contraceptive method.

Many women with complex medical conditions who do not wish to become pregnant are not receiving in-depth contraception counseling from their primary or subspecialty care clinicians, and often they are not using contraception, Mody said. Several, she added, have conditions that could worsen with pregnancy or for whom pregnancy could be complicated by the medical condition.

“You can have a big impact in a woman’s life if you are able to identify that she has a need for more contraceptive counseling. If the recommendation is for a patient to prevent pregnancy at this point in her life, we want to help her achieve that,” said Mody.

She is supported through an institutional NIH K12 award and mentored by UC San Diego Clinical and Translational Research Institute (CTRI) Executive Committee member Christina Chambers, Ph.D., M.P.H.

Groundbreaking work

“The work Dr. Mody is doing is groundbreaking in terms of preventing ‘preventable’ birth defects,” said Chambers, a professor of pediatrics at UC San Diego. “When we are prescribing medications known to have the potential to cause birth defects, it is essential to couple this with effective contraception counseling.”

A family planning fellowship-trained specialist can also recommend contraceptive methods that won’t interfere with therapy. For example, if a patient is taking medication for epilepsy and is concerned about drug-drug interactions, the specialist might recommend an intrauterine device rather than an oral contraceptive.

Mody said bringing the five medical campuses together with inter-institutional support and resources has a greater impact on patient health. The collaborative partners include UC Davis, UC Irvine, UCLA, UC San Diego and UC San Francisco.

“In order to progress the research knowledge about family planning with these medical conditions, it is helpful to have the UCs work together so we can improve patient care,” Mody said.

The UC partnership is also important for tackling state-specific research questions and policy issues.

UC ReX employed for research data

The collaborative employed UC Research Exchange (UC ReX), an initiative of UC Biomedical Research, Acceleration, Integration, and Development (UC BRAID), a consortium of the five UC medical center campuses. The UC ReX Data Explorer is a secure online system that enables cross-institution queries of clinical aggregate data from 13.6 million de-identified records. The collaborative then used the UC systemwide IRB Reliance Registry to streamline its administrative processes. Reliance is a regulatory initiative that enables UC campuses to rely on the Institutional Review Board (IRB) approval received by another UC campus.

“We began by using UC ReX. We wanted to get numbers of potential participants with different diagnoses. UC ReX enables us to search by age, gender, medical condition or diagnosis, and we were able to get rough estimates,” Mody said.

Through CTRI, the researchers also used Research Electronic Data Capture (REDCap) for data entry. REDCap is a secure Web application for building and managing online surveys and databases.

“All of these tools have definitely helped us launch this project,” said Mody.

UCOP and each medical center campus provided funding for the study.

“We received a generous grant to do our first research together and develop the collaborative as a whole,” Mody said.

The effort included combining its family planning journal clubs and salary support for research assistants at five study sites.

“Seeing the concept come to life has been very fulfilling. Everyone’s hard work, dedication and vision for the study’s potential have really contributed to its success,” she said. “The key is not to work in silos.”

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Quest to create real-world tricorder

XPRIZE teams will test Star Trek-inspired medical devices at UC San Diego.

Mark 1 tricorder from the Star Trek TV series.

By Scott LaFee, UC San Diego

Seeking to boldly go where medical science has not gone before, the Clinical and Translational Research Institute (CTRI) at UC San Diego has been named the official testing site for the $10 million Qualcomm Tricorder XPRIZE, a global competition sponsored by the Qualcomm Foundation to develop a consumer-friendly, mobile device capable of diagnosing and interpreting 15 physiological conditions and capturing vital health metrics.

The XPRIZE competition is inspired by the tricorder medical device that debuted in the original 1966 “Star Trek” TV show and was frequently featured in subsequent series and movies.

“Of course, the tricorder in ‘Star Trek’ was originally fantasy, a wonderful bit of science fiction,” said Gary S. Firestein, M.D., CTRI director, dean and associate vice chancellor of translational medicine at UC San Diego. “But the idea – and this XPRIZE competition – symbolizes a very real vision of how we can shape a healthier future with creative use of cutting edge discoveries. It’s emblematic of our focus on ‘disruptive innovation’ to improve human health. We are looking forward to working with XPRIZE in the quest to seek out new technologies.”

CTRI will serve as the physical location of the test program, with doctors, technicians and staff providing logistical and personnel management. CTRI will be responsible for recruiting up to 480 volunteers to serve as consumer-testers, gaining their consent and instructing them in the use of the devices, overseeing device testing and conducting follow-up surveys.

Late last year, 10 teams were selected as finalists for the Qualcomm Tricorder XPRIZE. The teams come from the United States, Canada, India, Taiwan, Slovenia and the United Kingdom, representing both academic and private enterprises.

Beginning in early summer and for several months, these teams will have their entries evaluated at UC San Diego on specific measures of health assessment and consumer experience. For example, the devices must accurately diagnose a set of health conditions, such as diabetes, atrial fibrillation, stroke, tuberculosis, chronic obstructive pulmonary disease, pneumonia and hepatitis A. They must also capture real-time health metrics, such as blood pressure, respiratory rate and temperature.

“A tricorder could empower patients to capture reliable diagnostic data that will help them self-evaluate symptoms they are having and better prepare them for discussing their symptoms with their health care team,” said Gene “Rusty” Kallenberg, M.D., professor and vice-chair, Department of Family Medicine and Public Health in the UC San Diego School of Medicine.

Final results will be announced in 2016 – the 50th anniversary of the original Star Trek series. First prize is $7 million, with $2 million for second place and $1million for third.

The CTRI testing site team will include physician-monitors, clinical coordinators, a database programmer and technical advisors. Kallenberg and a physician oversight team will direct preparatory tasks prior to testing, then medically monitor emergencies, field medical questions and handle issues requiring medical opinion or interventions during testing.

Coordinators trained in managing clinical trials will oversee the XPRIZE testing experiences of consumer-testers. The database programmer will program and produce reports to identify potential consumer-testers by location and/or department or by disease condition.

The team will also include staff from the Qualcomm Institute at UC San Diego to provide technical support. The Qualcomm Institute’s role will be to capture relevant data from the multiple participants in the test scenario (the tricorder, the consumer tester, the XPRIZE on-site technician and the on-site test monitoring tools), transfer that data to a central repository and perform review, analyses and scoring based upon captured metrics.

Testing will occur at CTRI’s Center for Clinical Research on the UC San Diego campus, UC San Diego Medical Center – Hillcrest, and at primary care clinics and some specialty clinics in the UC San Diego Health System.

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UC San Diego, UCSF launch new Cancer Cell Map Initiative

Collaboration aims to determine how all of the components of a cancer cell interact.

Cultured HeLa cancer cells. (Image by Thomas Deerinck, National Center for Microscopy and Imaging Research, UC San Diego)

Researchers from the UC San Diego School of Medicine and UC San Francisco, with support from a diverse team of collaborators, have launched an ambitious new project – dubbed the Cancer Cell Map Initiative or CCMI – to determine how all of the components of a cancer cell interact.

“We’re going to draw the complete wiring diagram of a cancer cell,” said Nevan Krogan, Ph.D., director of the UC San Francisco division of QB3, a life science research institute and accelerator, an investigator at Gladstone Institutes and co-director of CCMI with Trey Ideker, Ph.D., chief of medical genetics in the UC San Diego Department of Medicine and founder of the UC San Diego Center for Computational Biology & Bioinformatics.

In recent years, progress in genome sequencing has made it possible to decipher hundreds of mutations found in a patient’s tumor. But in only a few cases do scientists understand how these mutations give rise to cancer or indicate what treatments to pursue.  More puzzling still, the mutations found in each patient are almost always different – even though they can lead to the same type of cancer.

It has long been thought that, while these mutations are unique to individuals, they hijack the same hallmark cancer pathways or genetic circuits. To interpret genomic data, researchers say the complete wiring diagram of the cell is needed, one that details all of the connections between normal and mutated genes and proteins.

“We have the genomic information already. The bottleneck is how to interpret the cancer genomes,” said Ideker.  A comprehensive map of cancer cells would help – and accelerate the development of personalized therapy, the central aim of “precision medicine.”

Krogan agreed: “The key to understanding genomic information is being able to place it into biological context. Mutations in tumor DNA that at first appear to be unrelated may in fact be clustered in specific pathways or multi-protein machines in the cell. The information, in context, will point to areas that we can target with specific therapies.”

The CCMI combines expertise at UC San Diego in extracting knowledge from big biomedical data sets with advances developed at UCSF for experimentally interrogating the structure and function of cells. It is a multimillion dollar collaboration between the UC San Diego Moores Cancer Center and the UCSF Helen Diller Family Comprehensive Cancer Center; funded by QB3 at UCSF, UC San Diego Health Sciences and support from Fred Luddy, founder of ServiceNow, a provider of enterprise service management software.

“The combination of medical research and high technology is our best opportunity to understand and rid the planet of insidious diseases like cancer,” said Luddy, who is a member of the Moores Cancer Center advisory board. “I am thrilled and flattered to have the opportunity to be able to support this great frontier.”

Scott Lippman, M.D., and Alan Ashworth, Ph.D., F.R.S., directors of the UC San Diego and UCSF comprehensive cancer centers, respectively, will provide access to tissue samples donated by patients being treated for cancer. The samples constitute a library of mutations associated with the disease.

“The CCMI is an example of the best kind of collaborative science,” said Lippman. “It draws together the strengths of multiple institutions and combines them in ways that are exponentially more powerful. And it is fundamentally driven by real people – actual patients with cancer. It is their stories, and the stories contained within their DNA, that will ultimately help us reveal cancer’s darkest and most difficult secrets.”

Added Ashworth: “Over the last few years, genome analysis has revealed many of the commonly occurring mutations in human cancer. Optimal exploitation of this will require a detailed understanding of how these genetic changes subvert normal cellular functions. The insights that this project will create will be critical in achieving this goal. I am tremendously excited to be involved in this initiative.”

The CCMI will provide key infrastructure for the recently announced alliance between UC San Diego Health Sciences and San Diego-based Human Longevity Inc., which plans to generate thousands of tumor genomes from UC San Diego cancer patients. It also will leverage resources and information from the National Cancer Institute (NCI), including large databases of cancer genomes and pathways that are being developed in collaboration with the San Diego Supercomputer Center and UC Santa Cruz.

David Haussler, director of QB3 at UC Santa Cruz and creator of the NCI Cancer Genomics Browser, said, “This is an exciting opportunity to utilize the unique NCI repository of 1.5 petabytes of cancer genomics data, combined with proteomic and functional data, to dive deeper into the molecular processes of cancer.”

Primary partners at UC San Diego are the Division of Genetics and the Department of Medicine in the UC San Diego School of Medicine and UC San Diego Moores Cancer Center. At UCSF: QB3, the Department of Cellular and Molecular Pharmacology and the Helen Diller Family Comprehensive Cancer Center.

Several other institutes, resources and biotechnology companies are also involved, including the Gladstone Institutes in San Francisco, the Clinical and Translational Research Institutes at both UC San Diego and UCSF and Thermo Fisher Scientific Inc., based in Massachusetts.

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Lens-free microscope can detect cancer at cellular level

UCLA researchers develop device that can do the work of pathology lab microscopes.

Tissue sample image created by a new lens-free microscope developed in the UCLA lab of Aydogan Ozcan. (Image by Aydogan Ozcan, UCLA)

By Bill Kisliuk, UCLA

UCLA researchers have developed a lens-free microscope that can be used to detect the presence of cancer or other cell-level abnormalities with the same accuracy as larger and more expensive optical microscopes.

The invention could lead to less expensive and more portable technology for performing common examinations of tissue, blood and other biomedical specimens. It may prove especially useful in remote areas and in cases where large numbers of samples need to be examined quickly.

The microscope is the latest in a series of computational imaging and diagnostic devices developed in the lab of Aydogan Ozcan, the Chancellor’s Professor of Electrical Engineering and Bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science and a Howard Hughes Medical Institute professor. Ozcan’s lab has previously developed custom-designed smartphone attachments and apps that enable quick analysis of food samples for allergens, water samples for heavy metals and bacteria, cell counts in blood samples, and the use of Google Glass to process the results of medical diagnostic tests.

The latest invention is the first lens-free microscope that can be used for high-throughput 3-D tissue imaging — an important need in the study of disease.

“This is a milestone in the work we’ve been doing,” said Ozcan, who also is the associate director of UCLA’s California NanoSystems Institute. “This is the first time tissue samples have been imaged in 3-D using a lens-free on-chip microscope.”

The research is the cover article today (Dec. 17) in Science Translational Medicine, which is published by the American Association for the Advancement of Science.

The device works by using a laser or light-emitting-diode to illuminate a tissue or blood sample that has been placed on a slide and inserted into the device. A sensor array on a microchip — the same type of chip that is used in digital cameras, including cellphone cameras — captures and records the pattern of shadows created by the sample.

The device processes these patterns as a series of holograms, forming 3-D images of the specimen and giving medical personnel a virtual depth-of-field view. An algorithm color codes the reconstructed images, making the contrasts in the samples more apparent than they would be in the holograms and making any abnormalities easier to detect.

Ozcan’s team tested the device using Pap smears that indicated cervical cancer, tissue specimens containing cancerous breast cells, and blood samples containing sickle cell anemia. In a blind test, a board-certified pathologist analyzed sets of specimen images that had been created by the lens-free technology and by conventional microscopes. The pathologist’s diagnoses using the lens-free microscopic images proved accurate 99 percent of the time.

Another benefit of the lens-free device is that it produces images that are several hundred times larger in area, or field of view, than those captured by conventional bright-field optical microscopes, which makes it possible to process specimens more quickly.

“While mobile health care has expanded rapidly with the growth of consumer electronics — cellphones in particular — pathology is still, by and large, constrained to advanced clinical laboratory settings,” Ozcan said. “Accompanied by advances in its graphical user interface, this platform could scale up for use in clinical, biomedical, scientific, educational and citizen-science applications, among others.”

In addition to Ozcan, the principal authors of the research were Alon Greenbaum, a UCLA Engineering graduate student and a research fellow at HHMI, and Yibo Zhang, a UCLA Engineering graduate student. Other authors were UCLA Engineering graduate student Wei Luo, undergraduate researchers Alborz Feizi and Ping-Luen Chung, and Dr. Shivani Kandukuri of the department of pathology and laboratory medicine at the David Geffen School of Medicine at UCLA.

The research was supported by the Presidential Early Career Award for Scientists and Engineers, the National Science Foundation, the National Institutes of Health, the Army Research Office, the Office of Naval Research and the Howard Hughes Medical Institute.

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Big data in biosciences, health care is focus of new UCLA research center

Institute for Quantitative and Computational Biosciences will advance biomedical sciences.

Alexander Hoffmann and his colleagues will collaborate with mathematicians to make sense of a tsunami of biological data. (Photo by Reed Hutchinson, UCLA)

By Stuart Wolpert, UCLA

A new research institute at UCLA may eventually provide doctors with tools to more accurately tailor medicines for individual patients, which could both improve quality of care and minimize the side effects associated with today’s medicine.

The Institute for Quantitative and Computational Biosciences will employ multidisciplinary research to study how molecules and genes interact. Its goal: unlocking the biological basis of health and disease by tapping the power of big data and computational modeling.

“UCLA’s Institute for Quantitative and Computational Biosciences will have a major, positive impact on human health,” said UCLA Chancellor Gene Block. “It will engage exceptional faculty from the life sciences and physical sciences, and our David Geffen School of Medicine and Henry Samueli School of Engineering and Applied Science to ensure that UCLA is at the forefront of research that will help usher in a new era of personalized health care, and to transform research and education in the biosciences.”

The institute is led by Alexander Hoffmann, professor of microbiology, immunology and molecular genetics in the UCLA College, whose research aims to understand how our genes interact to ensure health or produce disease — and the roles played by such factors as food, environmental stresses, infectious agents and pharmaceuticals. Among the diseases for which Hoffmann’s research may lead to significant progress are cancer and immune disorders, because they are caused by errors in cellular decision-making.

Hoffmann says that biology’s million-dollar question is how genes and environment interact to ensure health or cause disease, he said. As UCLA researchers work to answer that question, they will collaborate with UCLA mathematicians who will create mathematical models that help them make sense of a tsunami of biological data.

“Biology is entering a new phase,” Hoffmann said. “So far, biology has been much less math-based than the other sciences. Since the sequencing of the human genome in the early 2000s, there has been an irreversible change in the way biology and biomedical research are being done. At UCLA, we will lead research in that direction and connect basic and applied sciences in an unprecedentedly productive collaboration.”

Victoria Sork, dean of the UCLA Division of Life Sciences, said the institute’s approach represents the “new life sciences” and predicts that the new center will accelerate discovery and translational application in many areas, including medicine, the environment, energy, and food production and food safety.

“Technological breakthroughs are enabling scientists to analyze not only one gene at a time, but how hundreds or thousands of genes work together,” Sork said. “Combined with big data, new knowledge of critical gene networks will lead us to a better understanding of what makes humans healthy.”

The road to “precision medicine”

Dr. A. Eugene Washington, vice chancellor of UCLA Health Sciences and dean of the David Geffen School of Medicine at UCLA, said the new era of personalized medicine will offer higher-quality health care — and possibly lower-cost care — because genetic information will give health providers better knowledge about individual patients.

“We are likely to see significant change in health care in the coming years as genetic data for individuals become more widely available,” Washington said.

In fact, big data already has begun to transform health care. In the past, doctors treating people with a certain disease might have relied solely on their own or their colleagues’ experience treating others with the same disease. Now, instead of relying on a small number of case studies, physicians can turn to mountains of data to guide their approach.

“We haven’t yet begun to fully tap into the knowledge we have about how we have treated millions of patients,” said Dr. Steven Dubinett, director of the UCLA Clinical and Translational Science Institute, and UCLA’s senior associate dean for translational research and associate vice chancellor for research.

“Now, with the rise of big data, we have the capability to utilize a network of brains in a highly sophisticated manner so that all our experience at UCLA, in the University of California system and the many other hospitals with which we share data can be brought to bear on patient treatment in a way that was not possible before.”

The result may be not only personalized health care, but “precision medicine”—the ability for doctors to accurately predict positive health outcomes for patients, Dubinett said.

The move to big data also is dramatically changing the skill sets required for life sciences and biomedical researchers: Increasingly, backgrounds in mathematics, computer science and physics will be highly sought after. Already, UCLA is planning new programs through which computational scientists will train clinicians so they can understand how to work with large sets of data and apply the insights they gain to treating patients.

In addition, UCLA has established a doctoral program in bioinformatics, and the Clinical and Translational Science Institute, in which UCLA is one of four partner institutions, is at the forefront of utilizing big data in clinical care — including developing new pharmaceuticals and bringing important new discoveries into the community.

Much of the data UCLA faculty will work with will come from the University of California Research eXchange, which manages an extremely large repository of clinical data — more than 12 million patient records. Dubinett said UCReX is in the process of adding millions of additional records through partnerships with other Los Angeles medical institutions and, eventually, other academic medical centers in California and throughout the U.S. (Patients’ identities are not released to researchers.)

Dubinett said UCLA will be a national leader in this revolution in personalized health care, in part because UCLA’s medical center is part of its main campus — something that is not the case at many other research universities. That close proximity makes it easier for doctors to collaborate with experts in biomedical informatics and other fields, and has been a lure for many of the exceptional scientists joining the effort.

To strengthen the new institute, UCLA has hired nine faculty members since July 2011 and has plans to hire additional faculty in the next several years. One of the new hires was Leonid Kruglyak, who came to UCLA from Princeton University in 2013. Kruglyak uses big data in his genetics research and, according to Sork, is a “brilliant superstar of the highest stature.”

Among the other outstanding faculty members UCLA has hired, Sork said, are two at the cutting edge of computational biology: Matteo Pellegrini, professor of molecular, cell and developmental biology, and Xinshu (Grace) Xiao, an associate professor of integrative biology and physiology. Both are in the UCLA College.

From individual genes to entire ecologies

Pellegrini, co-director of the institute, said the move to big data also will enable scientists to significantly broaden the scope of their research.

“We’re going from a paradigm where scientists studied individual genes to one in which they will study organisms and even entire ecologies — sequencing the genomes of communities of organisms and understanding how they interact,” Pellegrini said. “Technology is making science very exciting, presenting enormous opportunities to revolutionize our understanding of biology at the genome-wide level and to apply these techniques to answer all kinds of questions.”

Hoffmann said that in the past, one of the major challenges in biology research was generating data. “Now, the challenge is how to make sense of a tsunami of scientific data, to discover the critical patterns and to tell the signal from the noise,” he said. “The opportunities to develop accurate predictions are unprecedented.”

“These examples are just the tip of the iceberg,” said Hoffmann. “The power of combining big data computational tools with computational modeling based on hard basic science is leading a revolution in the bio- and health sciences that provides unimagined opportunities to humanity.”

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New drugs from fish oil could air artery repair

Interdisciplinary collaboration key to translating academic research into tangible innovations.

Kevin Lance, a graduate student in Tejal Desai's lab, holds up a tiny "wrap" that could be placed around an artery or vein and slowly release a fish oil-derived drug to prevent vascular scarring. (Photo by Kathleen Masterson, UC San Francisco)

By Kathleen Masterson, UC San Francisco

Every year, more than a half-million Americans undergo procedures to have a narrowed coronary artery propped open with a small metal mesh tube, or stent. The procedure is common for certain patients who’ve experienced a heart attack or other arterial blockages, and it helps to restore blood flow.

But in about 1 in 4 cases (1 in 3 if it’s your leg artery), the vasculature tissue starts renarrowing again after the procedure, effectively regrowing the blockage. The problem of excessive vascular scarring isn’t limited to stents, but also affects many other common procedures such as angioplasty, bypass surgery, and placement of fistulas or grafts for patients on dialysis.

“When we operate on an artery it always causes an inflammatory reaction and a subsequent scarring response just like anywhere else on your body, even the skin,” said Michael S. Conte, M.D., chief of vascular & endovascular surgery at UCSF.

If this inflammation continues, the cells surrounding the tiny metal cage still treat the area as injured, and ultimately grow back in.

But a common class of naturally occurring molecules from fish oil could change all that.

It turns out that when the body heals naturally it’s a two-step process: first it generates compounds to promote inflammation, and when those wane, the body sends in a second set of compounds that actively stops inflammation.

These anti-inflammation signaling compounds are derived in the body from dietary fish oil, and Conte and collaborators Charles Serhan of Harvard University and Tejal Desai, Ph.D., chair of the UCSF Department of Bioengineering and Therapeutic Sciences, are using them to develop treatments to prevent ongoing inflammation in blood vessels.

Desai has been working on stents from a different angle; her lab at the School of Pharmacy focuses on therapeutic microtechnology and nanotechnology. If successful, their collaboration could help prevent arteries and veins from closing up again after surgeries, such as a stent implant or an angioplasty, a procedure where a balloon is temporarily inserted into the artery or vein to open it up.

“What we’re trying to do is turn an angioplasty into a mosquito bite: we want it to get injured and resolve, not get injured and scar,” said Conte.

Interdisciplinary collaboration like that of Desai and Conte is key to translating academic research into tangible innovations. Partnering with industry is also vital in getting technologies to patients: UCSF’s Innovation, Technology and Alliances supports hundreds of researchers to make science come alive by procuring licenses, partnering with industry sponsors and filing patents.

ITA helped Conte and Desai file a patent for their combination drug-device approach. Theirs is one of 48 patent filings this fiscal year, while overall UCSF holds a total of 631 active patents. Additionally, ITA negotiated nearly 400 industry-sponsored research deals and new clinical trial agreements.

Conte and Desai also won an NIH grant that specifically funds promising vascular research that could be translated into a medicinal use. The grant keeps them on a tight timeline to get their product up to speed for testing in humans.

To date, Conte has shown the drug reduces vascular scarring in mice and rabbits after they undergo an angioplasty. Not only did the drug lead to less scar tissue build-up, but they found a reduction in the presence of white cells weeks later, suggesting healing was accelerated.

With the help of UCSF’s Innovation, Technology & Alliances team, the researchers have filed a patent for their combination drug-device approach.

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UC translational medicine leaders chart course

UC BRAID holds annual retreat in San Diego.

UC BRAID program leaders (from left): Jennifer Grandis (UC San Francisco), Lars Berglund (UC Davis), Deborah Grady (UC San Francisco), Steven Dubinett (UCLA), Gary Firestein (UC San Diego) and Dan Cooper (UC Irvine). (Photo by Courtney McFall, UC San Francisco)

By Patti Wieser, UC San Diego

With plans to “think boldly” about the next phase of integrating resources and talent, representatives of the University of California Biomedical Research Acceleration, Integration, and Development (UC BRAID) program staked out future directions during the annual retreat Nov. 7 at UC San Diego. Plans on the horizon include integrating informatics across the UC enterprise, expanding UC Research Exchange (UC ReX – a federated multisite clinical data repository), developing industry partnerships, and expanding the systemwide network for clinical and translational research.

The meeting, which focused on innovation, collaboration and acceleration, drew more than 80 translational medicine researchers, administrative leaders, staff and faculty representing eight UC campuses. The participants also discussed major achievements and potential new areas of focus.

“We are extremely excited about our progress as we continue to create an environment that decreases barriers to biomedical research and creates new tools to facilitate research,” said Gary S. Firestein, M.D., UC BRAID chair, director of UC San Diego Clinical and Translational Research Institute (CTRI) and dean and associate vice chancellor of translational medicine at UC San Diego. “UC BRAID serves as a model for collaborative consortia.”

Established in 2010, UC BRAID, in collaboration with the University of California Office of the President (UCOP), is a joint effort of the five UC biomedical campuses to catalyze, accelerate and reduce the barriers for biomedical, clinical and translational research across the UC system. The UC BRAID consortium — UC Davis, UC Irvine, UCLA, UC San Diego and UC San Francisco — pools data, resources and expertise to reach this goal. UC Riverside, UC Santa Barbara and UC Santa Cruz and UCOP also participated in this year’s UC BRAID meeting.

Lars Berglund, incoming chair of UC BRAID, welcomed the retreat participants. “BRAID is not a goal. It is a means for reaching our goals,” said Berglund, M.D., Ph.D., director of the Clinical and Translational Science Center and senior associate dean of research at UC Davis. The retreat provided a snapshot of “who we are” and energized the participants to continue fulfilling BRAID’s mission. “Enhancing collaboration between the UC system partners will advance the translational research initiative by disintegrating barriers that have evolved,” he said.

Rachael Sak, R.N., M.P.H., director of UC BRAID, discussed the evolvement of UC BRAID during her presentation about leveraging a UC network. “We have a shared vision: to integrate resources and talent across UC to accelerate research that improves health. We are leveraging these, developing Institutional Review Board (IRB) and contracting metrics, and shaping into a collaborative network,” she said. Sak, noting how far the organization has progressed since it was established, cited the following two major successes of UC BRAID during this past year:

Cross-UC clinical trial recruitment: Building upon its accomplishments in cohort discovery and IRB reliance, UC BRAID is developing more advanced cross-campus participant recruitment strategies and services.

National leadership in NIH National Center for Advancing Translational Sciences (NCATS) projects: UC BRAID is at the core of two recent initiatives, Accrual to Clinical Trials and IRB Reliance, supported by NCATS to enable a national network that can conduct large, multicenter clinical trials.

William Tucker, interim vice president of research and graduate studies and executive director of Innovation Alliances and Services with UCOP, presented a talk, “Leveraging UC’s research enterprise for value: President Napolitano’s initiatives that involve research.” Tucker said these initiatives include stimulating research and discovery in areas of strategic importance that benefits California and the world, and improves human lives, the environment and the economy. He lauded BRAID for doing a “great job” of organizing itself and leveraging the system and common practices. Tucker’s takeaway message was: “Think boldly.”

Other presenters were Mike Palazzolo, director of UC BRAID Center for Accelerated Innovation; Doug Bell, chair of UC ReX; Mike Caliguiri, project director for IRB metrics; Eric Mah, project director for IRB reliance; and Dan Dohan, project director for EngageUC. Breakout sessions at the retreat focused on biobanking and biorepositories, child health, contracting, regulatory, drug and device discovery and development, and UC ReX.

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6 translational science trends that will improve your health

Trends highlighted in podcasts range from team science to big data for health.

By Deborah Grady, UC San Francisco

Translational science, also known as bench-to-bedside research, aims to translate biomedical discoveries into useful applications and treatments, such as a drug, device, diagnostic or behavioral intervention, that impact health and health outcomes.

At UC San Francisco, my colleagues and I at the UCSF Clinical and Translational Science Institute (CTSI) are collaborating and innovating in ways that are transforming health care as we know it.

We’re also looking ahead at the trends and influences that are reshaping – and more importantly, accelerating – translational science, all with a focus on improving health. We partnered with Carry The One Radio to produce podcasts on each of the trends.

Learn more about the podcasts or listen to the full playlist here.

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