One Neuroscientist’s Quest to Create Healthier Brains

Photo by Elisabeth Fall

When Bruce Miller was recruited to UC San Francisco by neurology chair Stephen Hauser, MD, and Nobel Prize-winning professor Stanley Prusiner, MD, in the late 1990s, the University had just lost funding for its state-sponsored dementia center.

Miller, MD, a behavioral neurologist from UCLA, would have to build a new center from scratch.

“It had been a neglected area, and I decided I was going to try to give the best possible care to everyone we saw, because what San Francisco really needed was great care for cognitive disorders,” says Miller, who launched the Memory and Aging Center (MAC) in 1998.

Now, expanding the reach of this work, Miller has been tapped to co-direct a new $177 million Global Brain Health Institute (GBHI).

Bringing Basic Science to the Bedside

In many ways, the trajectory of Miller’s work is emblematic of the integration seen within the entire neurosciences field over the last decade, as its broad range of disciplines become increasingly interdependent and attract unprecedented levels of investment.

Today UCSF has one of the largest and strongest neuroscience communities in the country, including the No. 1-ranked neurology and neurosurgery departments in National Institutes of Health (NIH) funding, the top neurology and neurosurgery residency programs, and one of the five leading PhD programs in neuroscience.

Bruce Miller and Bill Seeley are tracing predictable patterns of a disease’s progression along brain circuits to help researchers diagnose patients with more accuracy and evaluate treatments by enabling them to visualize whether a drug halts or alters a disease’s path. Photo by Susan Merrell

A major emphasis of Miller’s clinical research at,the MAC, for instance, is diagnostic brain imaging, bringing new dimensionality to clinicians’ patient assessments, which previously were based primarily on behavioral patterns. Using advanced MRI technology, Miller and MacArthur “genius” Bill Seeley, MD, are tracing predictable patterns of a disease or disorder’s progression along brain circuits. These patterns help researchers diagnose patients with more accuracy and evaluate treatments by enabling them to visualize whether a drug halts or alters a disease’s path.

Such diagnostic imaging also will be used to evaluate the effectiveness of potential new drugs that Prusiner is developing just one floor above in the Sandler Neurosciences Center. Prusiner has partnered with Daiichi Sankyo, a leading Japanese pharmaceutical company, to create a fully automated microscopy screening system that can run 24 hours a day, seven days a week. In the past year, these rapid, high throughput screening procedures have yielded promising drug candidates for neurodegenerative diseases.

Miller’s work is evidence that basic science can and does find its way to the bedside. 

“One of my big goals was to build a center where someday, Stan Prusiner’s work in basic science and drug discovery would come directly into my patient population,” says Miller. Right now, in fact, the MAC has 80 translational projects in process and hundreds of patients participating in dozens of the most advanced clinical trials the field has to offer.

Miller continues to meet monthly with Hauser and Prusiner so that they can keep abreast of each other’s work and how it could be applied in the clinic.

An Inspirational Model

Today, the MAC hosts more than 3,000 patient visits a year, and it served as a primary inspiration for the new Global Brain Health Institute. The institute – which Miller will co-direct with Ian Robertson, PhD, chair of psychology at Trinity College Dublin and founding director of the Trinity College Institute of Neuroscience – was established with a $177 million gift from Atlantic Philanthropies.

Stephen Hauser, chair of neurology, and Stanley Prusiner, Nobel Prize-winning professor, have been leading neuroscience research at UCSF for decades, and were instrumental in recruiting Bruce Miller to UCSF. Photo by Cindy Chew

The GBHI will train and connect 600 cross-disciplinary leaders from all over the world so that they can apply their scientific and clinical expertise to create culturally appropriate practices and preventions in their home countries. In turn, they will nurture a new cadre of local leaders.

“We have tried to build a program that Chuck Feeney, founder of Atlantic Philanthropies, would be proud of,” says Miller, who holds the A.W. and Mary Margaret Clausen Distinguished Professorship in Neurology. “By focusing on underserved populations using cutting-edge science – whether it is social science, arts or basic science, we will use them all – to deliver better care to people across the world and in particular to protect people from age-related neurodegenerative conditions.”

Including the GBHI gift, the neurosciences at UCSF will have benefited from a wave of approximately $300 million in philanthropic investment over the last two years. This influx of private philanthropy has been earmarked for many areas, including basic science, education and clinical research.

With this gift, Feeney’s Atlantic Philanthropies support for UCSF has blossomed to approximately $500 million, and the organization is the single largest contributor to the University of California system.  

Investing in the Brain

Recent investments in UCSF neurology and neurosciences – on both the public and private level – point to the incredible depth of the research here and its potential to produce breakthrough treatments for dementia, mood disorders, traumatic brain injury and many other areas.

Here is an overview of the highlights from the past few years:

Private Philanthropy

Kavli Institute for Fundamental Neuroscience ($20 million) – The Kavli Foundation’s gift will establish a research institute focused on gaining a deeper understanding of plasticity, the brain’s remarkable capacity to modify its own structure and function.

Child, Teen and Family Center ($50 million) – An anonymous donor’s gift will establish a new center, scheduled to open in 2019, offering an  array of mental health services and provide a base for research and training to advance the prevention and treatment of mental illness.

Mood Disorders Research ($20 million) – The Ray and Dagmar Dolby Family Fund’s gift supports the Department of Psychiatry’s research on mood disorders, aiming to rapidly advance the understanding and treatment of depression, bipolar disorder and related illnesses.

Public Grants

SUBNETS Initiative for Psychiatric Disorders ($26 million) – The Defense Advanced Research Projects Agency (DARPA) funded this project as one of the first launched in support of President Obama’s Brain Initiative. Led by UCSF’s Edward Chang, it employs advanced technology to better understand and treat common, debilitating psychiatric disorders.

Dementia Care Ecosystem ($10 million) – The Centers for Medicare & Medicaid Innovation’s grant to UCSF and University of Nebraska Medical Center creates a web-based model of dementia care to provide around-the-clock consultations for patients and their families, online education and remote monitoring.

Traumatic Brain Injury Clinical Trials ($17 million) – The Department of Defense funded an unprecedented, public-private partnership, led by UCSF’s Geoffrey Manley, to drive the development of better-run clinical trials and may lead to the first successful treatments for traumatic brain injury.

“This is an extraordinary moment in UCSF’s history, as we revolutionize care for people that bridges the fields of psychiatry, neurology and neurosurgery – areas that were traditionally thought of as separate,” said Hauser, who's also the Robert A. Fishman Distinguished Professor of Neurology.

“The incredible generosity of Atlantic Philanthropies is pivotal for us as we generate unprecedented momentum and enable creative new research that will change the face of our understanding of and treatments for dementia and other neurological conditions.” 

Focusing on Prevention

Achieving Miller’s, and now the GBHI’s, global vision means creating model programs in San Francisco and Dublin that can be replicated around the world. For Miller, that means growing the MAC from its sweet spot at the intersection of basic science and clinical care.

The GBHI is focused on the approximately 30 percent of dementia/brain disease that researchers believe is preventable. Such causes include smoking, depression, a lack of exercise, obesity, untreated hypertension, falls that lead to catastrophic results, or delirium that goes untreated. 

The need is overwhelming. Alzheimer’s disease is the fifth leading cause of death in the United States – killing one in three seniors – and it is the country’s biggest killer, in terms of health care costs. Alzheimer’s, which is on the rise, has a $203 billion price tag.

This situation is much the same in every country with a sizable elderly population around the world, according to Miller.

“A third of the $200 billion this country spends on Alzheimer’s and related disorders could probably be cut if we just instituted the right policies across the United States,” says Miller, who last year received a grant from the Centers for Medicare and Medicaid Services to create a web-based model for dementia care that will help provide round-the-clock consultations for patients and their families. “We can think of what can be achieved in our own cities, San Francisco and Dublin, as microcosms and translate our successes to other parts of the world.”

The microcosm Miller envisions will be transdisciplinary – spanning sectors and disciplines. “We will bring health economists, public policy leaders, artists, poets and many more into our midst to think about how their specialties can lead to better health for our aging population,” says Miller. “Together we will ask, ‘How can we diminish cardiovascular risk factors, loneliness, isolation and sadness, which we know are risk factors of cognitive decline.”

Bolstering the Ranks in Neuroscience

The GBHI is also about bolstering the ranks of scientists and clinicians in the neurosciences. The institute will take the most talented and ambitious people across the world into UCSF’s training programs and teach them about neuroscience, the growing epidemic of dementia, public policy interventions and health economics.

Miller is confident that GBHI will have a firm foundation of talent at UCSF. “I have a Nobel prize-winning scientist on the floor above me; I am meeting with Peter Walter, a Lasker Winner, and Gladstone Neuroscience Director Lennart Mucke, about potential drugs for our patients that they have developed; and I am working with the best trainees in the world,” says Miller. “Where else can you do that?”

Miller is never more excited than at the prospect to heal and learn.

“I feel like every year I have been here it’s like going to medical school all over again. The GBHI is going to be the last chapter of medical school that I get to participate in,” Miller says. “It’s going to teach me so much that I don’t know about: health economics, public policy. I am thrilled at this chance now.”