TAG: "brain"

Total recall


UC Irvine memory expert James McGaugh recalls the heady days of a young university.

UC Irvine neuroscientist and founding faculty member James McGaugh stands in front of the campus building that is named after him. (Photo by Steve Zylius, UC Irvine)

By Scott Martelle

It was the winter of 1964, and James McGaugh already had what he considered a dream job. He’d earned a doctorate in psychology at UC Berkeley in 1959, taught for a few years at San Jose State College, done some postdoctoral work in Rome for a year, and then landed at the University of Oregon teaching and researching how the human brain works. “I was treated like a little prince up there,” McGaugh says. “They gave me everything I wanted. … I loved it there.”

Then the phone rang. McGaugh’s dissertation adviser from Berkeley was on the line, telling him about this new campus the University of California was creating on empty pastureland in a place called the Irvine Ranch. He suggested McGaugh put his name in to become the founding chair of an interdisciplinary department to study the brain and behavior.

It would be “the very first one in the world. And I was 32 years old,” says McGaugh, who followed the advice and was offered the position. “For a 32-year-old kid to get the opportunity to create a department of this kind – and to have full responsibility for that – I mean, that’s just mind-boggling. And I took it.”

He never left. As UCI nears its 50th birthday, McGaugh is one of only a few of those founding faculty and administrators who are still productive members of the campus community. His role has ranged from teaching to research to administration – he was executive vice chancellor for a while and is a co-founder of UCI’s Center for the Neurobiology of Learning & Memory (cnlm.uci.edu). But at heart, McGaugh has been a researcher, doing groundbreaking work on how the brain creates memories, which earned him election to the National Academy of Sciences.

It was work, he says, that he couldn’t have done anywhere else. Had he stayed in Oregon, McGaugh “probably would have been isolated and, over the long haul, … gravitated into teaching” and left research. “This was really, really good for me. Just amazing. Hell of a ride,” he says of his career at UCI. “I couldn’t have achieved, I don’t think, what I’ve achieved at any other place. I mean, it’s just incredible.”

At the age of 82, McGaugh remains active in his field, making regular trips to conferences and working within the CNLM. His continued involvement with UCI gives him a rare vantage point from which to view the university’s evolution from open ranchland to top education and research institution with more than 29,000 students, 1,100 faculty members and 9,700 staff members.

Rounding up the team

McGaugh arrived at UC Irvine in June 1964, about 14 months before the campus would open for its first students. His job was to recruit teachers and researchers for the new brain and behavior department (later called the Department of Neurobiology & Behavior), develop the curriculum and begin managing what would become one of the premier programs in the nation.

It was a position that held bright promise but also carried significant risk for a young research scientist – a risk McGaugh says he didn’t fully appreciate at the time.

“I was not sophisticated enough to know that it could have been the end of my scientific career, because that’s a heavy administrative load,” he says, sitting in his sun-drenched corner office in the CNLM’s Qureshey Research Laboratory. “But it was not the end of my scientific career, so I had a good time afterward. Those were wonderful days – terrific days.”

McGaugh recalls a relatively small cadre of administrators and faculty working to launch the university for the 1965-66 academic year and to foster its growth in the ensuing years. UC regents intended UCI to reach parity with UCLA, UC Berkeley and the other existing campuses, so recruiters for the Irvine campus targeted top talent.

“All of the deans who were eligible for the National Academy of Sciences when this place was founded were elected to the National Academy of Sciences after they got here,” McGaugh says.

Three of the early wave of faculty – Leland H. Hartwell, Frederick Reines and F. Sherwood Rowland – went on to win Nobel Prizes, though Reines’ was for work on neutrinos that he did before arriving at UCI and Hartwell’s was for work on cell growth after he left. Rowland’s Nobel recognized his discovery – at UCI – that man-made chemicals were eroding the Earth’s atmospheric ozone layer.

Blazing the trail

“We were just loaded with outstanding leadership, very high-achieving people who had positive outlooks on what [UC Irvine] was going to be,” McGaugh says. “The optimism was just around. It was fun.”

He credits some of those visionaries with laying solid groundwork and making pivotal hiring decisions.

Founding biological sciences dean Edward Steinhaus, he says, was instrumental in developing the biological programs and changing how universities structure the study of sciences, opting for an interdisciplinary approach over the traditional and more isolated “silo” approach.

“He originated the organization of biological sciences as it is today, divided in terms of levels of analysis rather than the kind of animals or plants that people work on,” McGaugh says, adding that UCLA and UC Berkeley eventually adopted a similar model. “He was really an intellectual pioneer.”

Surprisingly, McGaugh says, he and the other administrators had little trouble attracting new hires to a campus that at the time barely existed. That newness, he believes, was part of UCI’s appeal.

“Nobody turned me down,” he says. “There was an infectious excitement about what we were doing here. It was almost like summer camp.”

Riding high

Tight friendships grew, a function of relative geographic remoteness and a shared sense of mission.

“We knew each other, and we felt we were building something,” McGaugh says. “And now it’s much more isolated than that. I don’t have a sense of building or the campus. I only have a sense of what my department is doing and what the center is doing.

“I don’t know what’s happening in sociology. I don’t know what’s happening in English or history or engineering. I used to know all of that, but I don’t anymore because the campus is too big. I mean, there’s nothing bad about that; it’s just a natural consequence.”

The modern UCI is mostly what the young McGaugh had hoped it would be – the differences due to the campus’s evolving mission, the decreases in state funding for higher education and radical changes in Orange County itself. UCI is ranked first among U.S. universities under 50 years old – and seventh worldwide – by the London-based Times Higher Education, and it often places 12th or above in national evaluations of public universities. Still, McGaugh sees room for improvement.

“If you look at where we’re ranked and what we’ve achieved across campus as a now well-established university, it’s damn good,” he says. “We have really built a great university. Is it as great as I would like it to be? The answer is no. And I think there’s no reason we couldn’t rank No. 2 or No. 3.”

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Statins reverse learning disabilities caused by Noonan syndrome


UCLA mouse study shows drugs overcome mutation, even in adult brain.

Alcino Silva, UCLA

UCLA scientists have discovered that statins, a popular class of cholesterol drugs, reverse the learning disabilities caused by a genetic disorder called Noonan syndrome.

Their findings were published online Nov. 10 by the journal Nature Neuroscience.

The disorder, which is caused by a genetic mutation, can disrupt a child’s development in many ways. It often causes unusual facial features, short stature, heart defects and developmental delays, including learning disabilities. No treatment is currently available.

“Noonan syndrome affects 1 in 2,000 people, and up to half of these patients struggle with learning disabilities,” said Alcino Silva, the study’s principal investigator and a professor of neurobiology, psychiatry and psychology at the David Geffen School of Medicine at UCLA. “Our approach identified the mechanism causing the disease, as well as a treatment that reversed its effects in adult mice. We are excited about these findings because they suggest that the treatment we developed may help the millions of Noonan patients with intellectual disabilities.”

While many genes contribute to Noonan syndrome, there is one gene that causes about half of all cases. This gene encodes for a protein that regulates another protein called Ras, which controls how brain cells talk to each other, enabling learning to take place.

Working with first author Young-Seok Lee, Silva studied mice that were genetically engineered to develop Noonan syndrome. They discovered that the predominant mutation that leads to Noonan creates hyperactive Ras, which disrupts cellular conversations and undermines the learning process.

“The act of learning creates physical changes in the brain, much like grooves on a record,” said Silva, who also is a member of the UCLA Brain Research Institute and UCLA Integrative Center for Learning and Memory. “Surplus Ras tips the balance between switching signals on and off in the brain. This interrupts the delicate cell communication needed by the brain to record learned information.”

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UCLA-led team wins grant to tackle concussions among football players


New ‘microlattice’ helmet material would reduce head injuries, track collision impacts.

Architected Lattice, a new material designed to replace the foam inside football helmets, absorbs energy from the impact of collisions in order to help prevent concussion and traumatic brain injury.

A team of researchers from UCLA and Architected Materials that is developing breakthrough technology to reduce the number and severity of head injuries to football players today (Nov. 13) was named a winner of the Head Health Challenge II.

The Head Health Challenge is part of the four-year, $60 million Head Health Initiative, which is sponsored by the National Football League, General Electric and Under Armour. It is focused on improving the prevention, diagnosis and treatment of concussions and traumatic brain injury. Seven winning research teams were selected from among more than 450 Head Health Challenge II entrants from 19 countries.

The award comes with a grant of $500,000 for research, testing and development of the technology in the first year, with the potential for another $1 million in the second year.

The UCLA–Architected Materials group is developing a novel, energy-absorbing microlattice material, Architected Lattice, to improve the performance of football helmets. The material, designed to replace the foam used inside of today’s football helmets, will help prevent concussion and traumatic brain injury by absorbing energy upon impact while limiting peak loads.

Architected Lattice is light and breathable, and can be enhanced with a strain-sensing “smart lattice” to detect and transmit data about the impact of a collision. This data could help engineers and product designers make further improvements in helmet design and performance.

“We are honored to have been selected by the NFL, Under Armour and General Electric, and excited about the potential impact of developing the next generation of helmet pads with the Architected Lattice,” said Larry Carlson, director of advanced materials at the Institute for Technology Advancement at the UCLA Henry Samueli School of Engineering and Applied Science. “We believe that in addition to preventing or reducing injuries from high-impact collisions on the football field, this material can be used in a variety of sports and recreational applications.”

The research team includes material designers from Ventura, California-based Architected Materials, mechanical impact experts from UCLA Engineering, and brain science specialists at the David Geffen School of Medicine at UCLA. Along with Carlson, the research’s principal investigators are Alan Jacobsen, co-founder of Architected Materials, and Dr. Christopher Giza, director of the UCLA Steve Tisch BrainSPORT Program and a professor of pediatrics and neurosurgery.

“One of the key innovations with our Architected Lattice technology is that it can be manufactured quickly and cost-effectively, which differentiates our technology from traditional 3-D printing techniques,” Jacobsen said.

In preliminary tests, the material has outperformed commonly used vinyl nitrile for reducing transmitted peak force, a key metric for helmet pads.

“In addition to offering the potential to reduce sports concussions, the helmet’s unique material functions as a sensor that monitors impact to the brain,” Giza said. “Collaborative efforts like these powerfully showcase UCLA research teams’ role in developing innovative new ways to benefit public health.”

With more than 500 neuroscientists throughout campus, UCLA is a leader in research to understand the human brain, including efforts to treat, cure and prevent traumatic brain injury and brain disorders such as Alzheimer’s disease and epilepsy. The BrainSPORT Program was founded by Giza in 2012 and supported by a $10 million gift in May from philanthropist Steve Tisch.

In this video produced by General Electric, Under Armour and the NFL, researchers display a new helmet liner that absorbs significantly more energy than current materials, better protecting athletes from brain injury.

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Tolman, behavior and academic freedom


UC Berkeley day of talks honors pioneering professor.

In Tolman Hall, Seth Rosenfeld, author of "Subversives," connected the dots from Edward Tolman's stand against the UC loyalty oath to the Free Speech Movement. (Photo by Barry Bergman, UC Berkeley)

If you’ve ever been to Tolman Hall, you probably reached it not by rigid adherence to a series of mechanical steps — start at West Circle, go up Hilgard Way, first right to the end of Morgan Hall, then first left and voila — but by navigating via the map in your head. That is, you pictured its location, and figured out a suitable route.

If you’d made the trip Monday, you would have learned it was the man who lent the aging psychology building his name, longtime UC Berkeley professor Edward Tolman, whose pre-World War II work with rats in mazes changed how we think about how we think. His groundbreaking insights laid the foundation for the discovery of what’s been called “the brain’s GPS” — the underlying neural machinery of the cognitive map — and this year’s Nobel Prize in Physiology or Medicine.

Edward Moser, who shared the 2014 Nobel with his wife, May-Britt Moser, and John O’Keefe, gave the keynote address at Monday’s daylong celebration of Tolman’s legacy. While Moser and fellow neuroscientist David Foster, of Johns Hopkins University, gave technical presentations on their clinical research — with due credit to Tolman’s pioneering work in psychology — others highlighted his role as a pioneer in the realm of academic freedom.

In 1949, as McCarthyism raged, Tolman took a high-profile stand against the special “loyalty oath” demanded of UC employees by President Robert Gordon Sproul and the Board of Regents. Although he was fired, he not only won back his faculty position but was instrumental in winning the fight against the oath, which was ultimately found to be unconstitutional.

“The issue I am concerned with involves not communists but liberals,” explained Tolman, reading a letter to Sproul at a meeting of the Academic Senate. “For, when one reads the second part of the oath again, one discovers certain ambiguities of statement and meaning which would make it very difficult for many of us liberals to be certain just what we were being asked to commit ourselves to.”

He further objected that because only individuals can “believe,” it was dangerous to require faculty to disavow membership in organizations that “believe in” the overthrow of the U.S. government. This, he said, was “neither good psychology nor good civil rights.”

In 1963, the year before the Free Speech Movement — whose support from the Berkeley faculty, said author and journalist (and one-time Daily Cal reporter) Seth Rosenfeld, was an extension of the loyalty-oath fight — Berkeley’s new psychology building was dedicated in his name.

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The brain’s ‘inner GPS’ gets dismantled


UC San Diego research builds on Nobel Prize-winning science.

Imagine being able to recognize your car as your own but never being able to remember where you parked it. Researchers at the UC San Diego School of Medicine have induced this all-too-common human experience – or a close version of it – permanently in rats and from what is observed perhaps derive clues about why strokes and Alzheimer’s disease can destroy a person’s sense of direction.

The findings are published online in the current issue of Cell Reports.

Grid cells and other specialized nerve cells in the brain, known as “place cells,” comprise the brain’s inner GPS, the discovery of which earned British-American and Norwegian scientists this year’s Nobel Prize for medicine.

In research that builds upon the Nobel Prize-winning science, UC San Diego scientists have developed a microsurgical procedure that makes it possible to remove the area of the rat’s brain that contains grid cells and show what happens to this hard-wired navigational system when these grid cells are wiped out.

One effect, not surprisingly, is that the rats become very poor at tasks requiring internal map-making skills, such as remembering the location of a resting platform in a water maze test.

“Their loss of spatial memory formation was not a surprise,” said senior co-author Robert Clark, Ph.D., a professor of psychiatry. “It’s what would be expected based on the physiological characteristics of that area of the brain,” which is known as the entorhinal cortex and is the first brain region to break down in Alzheimer’s disease.

But the rats retained a host of other memory and navigation-related skills that scientists had previously speculated would be destroyed without grid cells.

“The surprise is the discovery of the type of memory formation that was not disrupted by the removal of the grid cell area,” Clark said.

Specifically, UC San Diego scientists were able to show that even without grid cells rats could still mark spatial changes in their environment. They could, for example, notice when an object in a familiar environment was moved a few inches and they could recognize objects, such as a coffee mug or flower vase, and remember later that they had seen these objects before.

Electrical recordings of signals transmitted from the hippocampus suggested that the animals had developed place cells – cells that are believed to convey a sense of location – and that these cells were firing when an animal passed through a familiar place.

“Their place cells were less precise and less stable, but they were present and active,” said Clark, who is also a research scientist at Veterans Affairs San Diego Healthcare System. “That was a surprise because we had removed the spatially modulated grid-cell input to these neurons.”

The axons of grid cells project into the hippocampus and it has been assumed that without this relay of information from the entorhinal cortex to the hippocampus, place cells would be unable to develop. “This is not the case,” he said.

“Our work shows a crisp division of labor within memory circuits of the brain,” he said. “Removing the grid-cell network removes memory for places but leaves completely intact a whole host of other important memory abilities like recognition memory and memory of fearful events.”

Co-authors include Jena Hales, Magdalene Schlesiger, Jill Leutgeb and Stefan Leutgeb, UC San Diego; and Larry Squire, Veterans Affairs San Diego Healthcare System and UC San Diego

This work was supported, in part, by the National Institute of Neurological Disorders and Stroke (1R01NS086947-01), National Institute of Mental Health (MH24600 and MH020002-13) and the Department of Veterans Affairs.

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Cal-BRAIN research program launched


First call for proposals has gone out.

Cal-BRAIN co-director Ralph Greenspan, who also heads up UC San Diego’s Center for Brain Activity Mapping.

Cal-BRAIN—a statewide research grants program that aims to revolutionize our understanding of the brain — is officially underway. The first call for proposals has gone out, and the program expects to announce its first awards in early 2015.

The program is seeking interdisciplinary teams from throughout the state to develop innovative new technologies for monitoring and analyzing wide-scale activity in the brain.

An initiative led by UC San Diego, Cal-BRAIN is short for California Blueprint for Research to Advance Innovations in Neuroscience. The program was signed into law in June and is the California complement to the federal BRAIN Initiative announced by President Barack Obama in 2013.

Ralph Greenspan, director of UC San Diego’s Center for Brain Activity Mapping, and Paul Alivisatos, director of the Lawrence Berkeley National Laboratory, are serving as Cal-BRAIN’s co-directors. Greenspan and Alivisatos are also co-authors of the initial proposals that led to both the BRAIN Initiative and Cal-BRAIN.

“We have laid the foundations for this important exploration of the brain in health and in disease, and we now look forward to being instrumental in the future of this research as well,” said UC San Diego Chancellor Pradeep K. Khosla. “UC San Diego is a natural leader to accelerate the development of ‘neurotechnology,’ as we have some of the world’s top scholars in both engineering and neurosciences.”

Cal-BRAIN has an initial allocation of $2 million. Seed grants in the first year will be a maximum of $120,000. Scientists from all California nonprofit research institutions are eligible to apply.

The call for proposals was approved by Cal-BRAIN’s California Advisory Board, which “represents all the major neuroscience research universities in California,” Greenspan explained.

To reduce the possibilities for conflict of interest, an out-of-state reviewing committee will assess the proposals. The first round of approximately 12 seed grants should be ready to announce by the end of January, Greenspan said.

“We’re eager to see the forward-looking research ideas that will come in,” said Greenspan, who is also associate director of the Kavli Institute for Brain and Mind at UC San Diego and professor in residence of neurobiology and cognitive science. “We have high hopes that California can play a major leading role in the national search for a better understanding of the brain.”

For more information on the program and to apply, visit the Cal-BRAIN website or write to info@cal-brain.org.

Cal-BRAIN is also seeking public input and will hold a Patients and Advocates Symposium on March 28 at the Sanford Stem Cell Consortium auditorium.

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Researcher receives award from American Academy of Pediatrics


Randi Hagerman honored with one of most prestigious awards for pediatricians in U.S.

Randi Hagerman, UC Davis

Randi Jenssen Hagerman, medical director of the UC Davis MIND Institute, Distinguished Professor of Pediatrics and Endowed Chair in Fragile X Research and Treatment, has received the prestigious C. Anderson Aldrich Award in Child Development for her outstanding contributions in the field of child development from the American Academy of Pediatrics (AAP), the professional organization for pediatricians in the United States.

The award recognizes pediatricians and non-pediatricians for their respective contributions to the field of developmental and behavioral pediatrics. It was presented at the American Academy of Pediatrics Section on Developmental and Behavioral Pediatrics national conference in San Diego on Oct. 12.

I am greatly honored by this award, humbled  after reading the list of previous recipients, and pleased that the AAP recognizes the importance of targeted treatments for individuals with neurodevelopmental disorders,” Hagerman said.

Hagerman is an internationally recognized clinician/scientist, director of the clinical trials program and founder of the Fragile X Research and Treatment Center at the MIND Institute. In 2001, with her husband, Paul J. Hagerman, UC Davis Distinguished Professor of Biochemistry and Molecular Medicine, she discovered fragile X-associated tremor/ataxia syndrome (FXTAS), a neurological disorder that affects older carriers of the fragile X premutation. In 1984 she co-founded the National Fragile X Foundation.

“This award is well-deserved recognition for Dr. Hagerman’s lifelong commitment to children with fragile X syndrome and their families,” said Leonard Abbeduto, Tsakopoulos-Vismara Endowed Chair of psychiatry and behavioral sciences and director of the MIND Institute. “She has helped thousands of people directly through her clinical care, and countless more through her groundbreaking research on the causes, consequences and treatment of FMR1-related disorders.”

“She also has trained and mentored a generation of pediatricians who will carry the field forward for decades to come,” Abbeduto continued. “It is certainly fitting that Dr. Hagerman is added to the list of luminaries who have received this award before her.“

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New target ID’d for personalized brain cancer treatment


UC San Diego finding focuses on a fusion protein.

Clark Chen, UC San Diego

Researchers at the UC San Diego School of Medicine have identified a new fusion protein found in approximately 15 percent of secondary glioblastomas or brain tumors. The finding offers new insights into the cause of this cancer and provides a therapeutic target for personalized oncologic care. The findings were published this month in the online edition of Genome Research.

Glioblastoma is the most common and deadliest form of brain cancer. The majority of these tumors – known as primary glioblastomas – occur in the elderly without evidence of a less malignant precursor. Secondary glioblastomas occur mostly in younger patients and progress from low-grade, less aggressive precursor tumors to glioblastoma, the most aggressive form of the disease.

“While genomic profiling is yielding improved understanding of primary glioblastoma, our understanding of secondary glioblastoma remains rudimentary,” said Clark Chen, M.D., Ph.D., vice chairman of research and academic development, Division of Neurosurgery, UC San Diego School of Medicine and a principal investigator of the study. “In this study, we used a technology called RNA-Seq to study the RNA sequences derived from 272 clinical tumor specimens from patients afflicted with secondary glioblastoma or precursor forms of this tumor.”

The study revealed that the RNA sequences of brain cancers become progressively more abnormal as the tumor become more malignant. Specifically, the frequency of aberrant RNAs fusing gene sequences not normally found next to one another increased with tumor grade. Most of these fusion junctions occur in seemingly random locations. However, transcripts involving fusions of the PTPRZ and MET gene were found repeatedly in clinical specimens derived from different patients. The study estimates that 15 percent of the secondary glioblastoma harbor this fusion.

“The recurrent nature of this fusion transcript suggests that the fusion did not arise by chance. Instead, it’s likely that the fusion actively contributes to the biologic behavior of the tumor,” said Chen, who collaborates with a multidisciplinary team at UC San Diego Moores Cancer Center. “Supporting this hypothesis, we demonstrated that glioblastoma cells expressing the PTPRZ-MET fusion are more invasive and patients afflicted with these tumors showed particularly poor survival relative to other secondary glioblastoma patients.”

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UC will lead effort to create library of brain cell activity


NIH program will advance fight against ALS, other neurodegenerative diseases.

Leslie Thompson, UC Irvine

UC Irvine will receive $8 million from the National Institutes of Health to establish one of six national centers dedicated to creating a database of human cellular responses that will accelerate efforts to develop new therapies for many diseases.

Leslie M. Thompson, UCI professor of psychiatry & human behavior and neurobiology & behavior, will partner with researchers from Cedars-Sinai Medical Center’s Regenerative Medicine Institute, the Gladstone Institute of Neurological Disease, UC San Francisco, Johns Hopkins University and the Massachusetts Institute of Technology.

They will study brain cell activity in motor neuron disorders including ALS and build a detailed archive of these disease “signatures” that identifies cell targets for new drug treatments. ALS, or amyotrophic lateral sclerosis, also called Lou Gehrig’s disease, attacks motor neurons, cells that control the muscles.

Overall, the NIH is awarding $64 million to six research groups to establish centers that support the Library of Integrated Network-Based Cellular Signatures program. The UC Irvine-based center will be called NeuroLINCS.

The goal of the LINCS program is to utilize the latest cutting-edge technology and scientific methods to catalog and analyze cellular function and molecular activity in response to perturbing agents – such as drugs and genetic factors – that have specific effects on cells. LINCS researchers will measure the cells’ tiniest molecular and biochemical responses and use computer analyses to uncover common patterns – called signatures. LINCS data will be freely available to any scientist.

“Human brain cells are far less understood than other cells in the body,” said Thompson, who’s affiliated with the Sue & Bill Gross Stem Cell Research Center and UCI MIND. “The collective expertise of NeuroLINCS investigators provides a unique opportunity to increase our knowledge of what makes brain cells unique and what happens during neurodegenerative diseases – with a strong focus toward effective treatments. We feel this will have broad application to a number of human brain diseases.”

She and her colleagues will study the effects, or signatures, of perturbing agents on induced pluripotent stem cell-derived neurons and glial cells from “unaffected” cells and those exhibiting the pathology of motor neuron diseases.

At UC Irvine, Thompson will work closely with the UCI Genomics High-Throughput Facility to explore gene expression patterns in these brain cells, which is expected to yield novel insights into pathways and gene networks that guide the development of cell signatures.

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UCSF, UC Berkeley scientists team up in new Center for Aging Research


Glenn Center exploring role of decline in protein quality-control in dementias, other illnesses.

Andrew Dillin, UC Berkeley

Researchers at UC San Francisco and UC Berkeley have teamed up to create an innovative, integrated center for research on neurodegenerative diseases. Supported by a $3 million grant from the Glenn Foundation for Medical Research, the new center aims to pave the way to developing novel treatments for diseases such as Alzheimer’s disease and Parkinson’s disease by investigating the many ways that proteins can malfunction within cells.

In particular, the center’s work will focus on a type of protein called the prion, which displays characteristics of infectious agents and is responsible for “mad cow” disease and a related, devastating human brain disorder known as Creutzfeldt-Jakob disease (CJD).

Stanley B. Prusiner, M.D., UCSF professor of neurology, and Andrew Dillin, Ph.D., the Thomas and Stacey Siebel Distinguished Chair of Stem Cell Research at UC Berkeley and a Howard Hughes Medical Institute investigator, will co-direct the new inter-campus program, known as the Paul F. Glenn Center for Aging Research. Ten additional researchers from UCSF and 13 from UC Berkeley will contribute to the center’s work, with more recruitments to come.

Stanley Prusiner, UC San Francisco

“The Glenn Foundation is pleased to welcome UCSF and UC Berkeley to the Glenn Consortium for Research in Aging,” said Mark R. Collins, president of the Glenn Foundation for Medical Research, which is based in Santa Barbara. “I had the pleasure to work with Dr. Dillin previously, when he led the Glenn Center for Aging Research at the Salk Institute for Biological Sciences prior to moving to UC Berkeley. I’ve known Dr. Prusiner and followed his work for many years and it is a propitious time for us to assist these two leaders in biological research to discover treatments for age-related neurodegenerative disease.”

In 1997, Prusiner, director of UCSF’s Institute for Neurodegenerative Diseases, received the Nobel Prize in Physiology or Medicine for his discovery of prions, which he demonstrated were an abnormally folded form of normal proteins that set up a template for replication in the brain. According to Prusiner, recent work provides persuasive evidence that, in addition to mad cow disease and CJD, many common neurodegenerative diseases, including Alzheimer’s and Parkinson’s, are caused by abnormally folded forms of normal proteins functioning as prions.

Dillin agrees that prions are ideal targets for research and novel therapeutic approaches. “The Glenn Foundation’s confidence to support our hypothesis is greatly appreciated,” he said, adding that the combination of UCSF’s medical mission with the strong basic research traditions of both campuses will make the new Glenn Center’s work uniquely powerful.

Proteins are crucial for many of a cell’s normal functions, but as people age, cells’ quality-control mechanisms become less efficient. Normally these systems ensure that proteins are properly formed, and target badly formed or “worn-out” proteins for destruction. But as the effectiveness of cellular quality control wanes over time, improperly formed proteins, including prions, can begin to accumulate.

Badly formed proteins, called “misfolded” by biologists, cannot carry out their required functions and, even worse, they can stick to one another and to other cellular components, sometimes leading to devastating physiological consequences. Prions are particularly problematic because they can act like a template, converting properly formed proteins into additional prions, essentially spreading protein misfolding like an infection.

Seeking ways to counteract the accumulation of misfolded proteins, the new Glenn Center’s researchers will investigate the many cellular quality-control mechanisms that act throughout a protein’s lifetime, from when proteins are first made, to the interactions that help them reach their proper functional state, to the transport processes that take them to their final destinations, to their ultimate degradation when they can no longer serve their purpose.

Together, the UCSF and UC Berkeley researchers affiliated with the center have complementary expertise in all of these areas, and the center’s ultimate goal is to develop new anti-prion drugs, Dillin said. “At Berkeley, we aim to build the basic scientific knowledge to leverage clinical and therapeutic discoveries at UCSF.”

According to Prusiner, “the newest research indicates that Alzheimer’s alone kills as many people every year as cancer does, but it only receives one-tenth of the funding that we dedicate to cancer research. We are grateful to The Glenn Foundation for their support in the battle against neurodegenerative diseases.”

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Tackling traumatic brain injury


Unprecedented partnership joins universities, FDA, firms, philanthropies.

UCSF neurosurgeon Geoffrey Manley (center) spoke at a White House conference Sept. 30 on the role of technology in future treatments for brain injury and post-traumatic stress disorder. Manley is flanked by Paul Alivisatos (left), director of the Lawrence Berkeley National Laboratory; and Kerry Ressler, a Howard Hughes Medical Institute Investigator from Emory University.

An unprecedented, public-private partnership funded by the Department of Defense (DoD) is being launched to drive the development of better-run clinical trials and may lead to the first successful treatments for traumatic brain injury, a condition affecting not only athletes and soldiers, but also millions among the general public, ranging from youngsters to elders.

Under the partnership, officially launched today (Oct. 1) with a $17 million, five-year award from the DoD, the research team, representing many universities, the Food and Drug Administration (FDA), companies and philanthropies, will examine data from thousands of patients in order to identify effective measures of brain injury and recovery, using biomarkers from blood, new imaging equipment and software, and other tools.

Each year more than 2.5 million people in the U.S. seek medical care for traumatic brain injuries that arise when blows to the body or nearby explosions cause the brain to collide with the inside of the skull. According to the U.S. Centers for Disease Control and Prevention, an estimated 2 percent of the U.S. population now lives with TBI-caused disabilities, at an annual cost of about $77 billion. No treatment for acute TBI and concussion has proved to be effective.

“TBI is really a multifaceted condition, not a single event,” said UC San Francisco neurosurgeon Geoffrey T. Manley, M.D., Ph.D., principal investigator for the new award and chief of neurosurgery at San Francisco General Hospital and Trauma Center (SFGH), a UCSF partner hospital. “TBI lags 40 to 50 years behind heart disease and cancer in terms of progress and understanding of the actual disease process and its potential aftermath. More than 30 clinical trials of potential TBI treatments have failed, and not a single drug has been approved.”

The new research initiative, called the TBI Endpoints Development (TED) Award, brings together leading academic clinician-scientists with innovative industry leaders in biotechnology and imaging technology, with patient advocacy organizations, and with philanthropies. The research collaborators will be collecting a broad range of long-term data from existing studies and databases, and integrating these into a dataset that can be interrogated for TBI associations and causes in a way that has never before been possible.

TED is specifically designed to overcome the difficulty in demonstrating the effectiveness of TBI drugs and medical devices by actively involving the FDA in clinical-trial design from the outset.

Although awareness of TBI has focused on athletes and warriors, the condition is widely prevalent across all populations, due to falls and motor-vehicle and other accidents.

“We know that the problem is far more extensive than reported,” Manley said. “We have evidence that even those patients who arrive at emergency rooms with signs and symptoms that suggest they’ve sustained a brain injury often are released with no indication of a possible TBI entered into their medical records, and with no recommendation for follow-up care.”

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UC receives nearly a quarter of NIH brain research grants


14 projects are led by researchers from six UC campuses.

The National Institutes of Health awarded UC researchers nearly a quarter of the $46 million in grants announced today (Sept. 30) in support of President Barack Obama’s BRAIN Initiative.

UC scientists have long been at the frontline of efforts to understand the brain’s inner workings — a pre-eminence reflected by the grants: Of the 58 NIH awards, 14 are projects led by researchers from UC Berkeley, UC Davis, UC Irvine, UCLA, UC San Diego and UC San Francisco.

Collectively, UC researchers will receive more than $10 million of the $46 million that the NIH is awarding for 2014.

“The human brain is the most complicated biological structure in the known universe. We’ve only just scratched the surface in understanding how it works — or, unfortunately, doesn’t quite work when disorders and disease occur,” said NIH Director Dr. Francis S. Collins in a statement. “There’s a big gap between what we want to do in brain research and the technologies available to make exploration possible.”

The BRAIN Initiative was launched last year by Obama as a large-scale federal effort to help scientists develop new tools and technologies to gain a deeper understanding of how the brain functions and to accelerate the creation of new treatments for neurological disorders.

“These initial awards are part of a 12-year scientific plan focused on developing the tools and technologies needed to make the next leap in understanding the brain,” Collins said. “This is just the beginning of an ambitious journey and we’re excited about the possibilities.”

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