The Beauty of Team Research: Del Monte Institute Tackles Neurological and Neuropsychiatric Diseases from All Fronts
After 30 years in the states, his Dublin brogue has softened to a barely-detectable lilt in the turn of certain words and phrases. But John Foxe, PhD, who came to America in 1986 to run Division I Track and Field for Iona College in New York City, hasn’t lost a bit of the engaging, convivial spirit or “craic” so characteristic of his Ireland roots.
Travel advisors note that if you stop and ask a Dubliner for directions, they’ll most likely take you there themselves—and entice you to stop for a pint along the way. That genuine delight in conversation and innate ability to form connections with others are traits easy to see in Foxe, a 50-year-old father of three who still has the lanky physique of a miler and possesses a brimming energy and curiosity not unlike his pediatric patients. A neurobiologist, Foxe has devoted his career to finding ways to improve the lives of people—primarily children—suffering from intellectual and developmental disorders such as autism and schizophrenia.
With more than 25 years of clinical and scientific experience in the field, he came from New York City’s Albert Einstein College of Medicine to Rochester in 2015 to take the helm of The Ernest J. Del Monte Institute for Neuroscience. For certain, his keenly present, vibrant personality helped make him an easy choice to lead a daunting charge. Since his arrival he has worked collaboratively to break down barriers between individual laboratories, centers and departments focused on the nervous system across the University, and sculpt multi-investigator teams to more competitively confront and solve the “wicked” problems slowing discovery. The aim is to significantly speed the translation of new discoveries, and more effectively treat and prevent humankind’s most deadly and debilitating neurological and neuropsychiatric diseases.
“It’s a bit like putting together a great relay team, where each runner brings a specialized set of abilities to form a winning unit,” says Foxe, who as former director of Research for Einstein’s Children’s Evaluation and Rehabilitation Center was responsible for uniting pediatric scientists in a similar way.
“I love drawing together like-minded individuals and trying to help them reimagine a framework for accomplishing something. Right now in neuroscience, we can’t move the needle without teams that tackle major problems from all fronts and multi-methodological, multi-scalar perspectives. There are fundamental neuroscientific questions that simply can’t be broached at the level of an individual laboratory or investigator.”
That a well-functioning nervous system depends upon precise communication and perfectly-timed signals across the wiring of the brain and spinal cord, is an irony not lost on Foxe.
“Everything depends on synchronicity, doesn’t it?” says Foxe. “In very simple terms neuroscience is all about improving our understanding of the connectivity between our neurons and the molecular soup that’s in our brains. That’s what creates your sensations, your perceptions and your cognition, and if there’s something wrong with your cognition, there’s either something wrong with the soup, or something wrong with the connectivity of the networks.”
Vice dean for Research Steve Dewhurst, PhD, says The Del Monte Institute is well-poised to become a national destination for people seeking advanced care for neurological disorders under Foxe’s collaborative vision.
“We have been on the verge of novel therapeutics in this area for many years and this movement will make them a reality,” he says. “As our knowledge of brain function explodes, Rochester is prepared to lead the next chapter of neuromedicine research that will translate these findings into meaningful interventions for afflicted patients, and effective disease prevention methods to advance the health of populations.”
A Devastating Puzzle of Disorders
Together, neuroscience-related diseases are the leading cause of disability in the U.S.—affecting 18.7 million people—and represent the most unmet medical need in the industrialized world.
There are more than 600 different types of devastating neurological disorders—diseases of the brain, spine, connecting nerves and muscles—including brain tumors, epilepsy, Parkinson’s disease, Huntington’s disease, muscular dystrophy, cerebral palsy, ALS and stroke, as well as lysosomal storage diseases (Tay Sachs, Gaucher, Krabbe, Batten) and less-familiar conditions such as frontotemporal dementia.
Neuropsychiatric disorders—which involve the structure and function of the brain in relation to specific psychological processes and overt behaviors—include childhood intellectual and development disabilities (autism, ADHD, fetal alcohol syndrome, tic disorders), neurodegenerative diseases (Alzheimer’s and dementia), psychosis (schizophrenia), mood disorders (depression, bipolar disorder, mania), neurotic disorders (anxiety, OCD, PTSD) addictions (chemical dependency, gambling), as well as eating and sleep disorders.
For the majority of these diseases, there is yet no definitive cure beyond ameliorative medications and therapies. Early and accurate diagnosis and intervention remain critical to improving quality and duration of life. The bulk of URMC research continues to focus on this important target, with prevention being the ultimate goal.
“These are the fundamental problems of humankind and they can only be solved by unraveling the deep mysteries of the brain,” says Foxe. “If you ask older people what their major health concern is, they won’t say heart disease, cancer, falls or even incontinence. Almost 95% will say, ‘I want my mind to stay sharp.’ We all expect to get frail and for our bodies to give up on us, but we don’t want our minds to give up on us. Our minds and memories are fundamental to who we are. We want to be present as long as we can with our kids and grandkids. Anyone who knows the horrors of advanced Alzheimer’s disease doesn’t want that for themselves or anyone around them. It’s a torturous way to pass your final years.”
Increasing the Bandwidth
Across the country, universities like Rochester are coming up against the limits of research as it has traditionally been done, Foxe says. The image in popular culture of the lone lab-coated researcher hitting upon a brilliant idea is fast becoming outdated.
Foxe meets with doctoral students in the Del Monte Institute's new administrative office space.
“Pick up the daily paper or peruse the Internet and one is beset with story after story about tough medical and societal challenges that won’t be solved with facts alone,” he says. “They have innumerable causes, are interconnected with other problems and rarely have single acceptable solutions. Hundreds of studies can be carried out, and still the answer can be elusive.”
Some of the blame lies in an all-too-common “loading dock” approach to science, which has been likened to scientists following the model of a factory where widgets are produced and then trundled out to the loading dock where someone eagerly waits to pick up the supposedly useful product. But the product may not, in fact, be at all useful to a patient if it doesn’t take into account the full set of complications in the real world.
“You can’t fault individual scientists for not thinking more broadly, because funding is so difficult, that their primary worry becomes just to keep their labs funded and open,” he says. “They develop their niche and what often happens is that when they’re asked to do something at the team level, they often just don’t have the bandwidth. In this way, the system has become inherently conservative—when the one discipline that can’t afford to be conservative is science.”
Solving today’s biggest health problems demands a more ambitious, complex approach, says Foxe. Researchers with different kinds of expertise need to put their heads together. Scientists and decision-makers need to interact regularly and become more familiar with each other’s worlds. Patients and families need to be closely involved, and novel funding streams need to be explored, including partnerships with industries and organizations.
“We need stakeholder-engaged, solutions-focused, interdisciplinary work if our scarce science resources are to be mobilized,” he says. “We have to alleviate resource worries so researchers can devote time to projects at the team level. That’s where philanthropy and private donors become crucial. You can’t expect the government to come in and do that. The government is mostly going to fund stuff that’s absolutely destined to work. That’s great, that needs to happen, but that’s not how new discoveries are made.”
A National Powerhouse
Assistant professor of Neuroscience Krishnan Padmanabhan, Ph.D., works with first-year neuroscience grad student Emily Warren. His lab explores, from a multisensory perspective, how memories shape our response to future experiences, and how this association is disrupted in neurological disorders.
Rochester, says Foxe, has a tradition of being “top of the class” in neuroscience and has the key ingredients, not only in the Medical Center but across the University, to create a new paradigm.
Dozens of widely published, internationally-regarded neuroscientists have made their mark in Rochester, such as Maiken Nedergaard, MD, DMSc (the role of the glymphatic system in eliminating brain toxins), Steve Goldman, MD, PhD (glial cell transplantation in Huntington’s disease and multiple sclerosis), Ray Dorsey, PhD, MBA (web- and mobile-based technologies and therapeutics for treatment of neurodegenerative diseases), Bradford Berk (MD/PhD ’81) (cellular mechanisms in the vascular system), Robert Griggs, MD (pharmacologic treatments for Duchenne muscular dystrophy), Marc Halterman (MS ’99, MD/PhD ’02, Res ’03, Flw ’06) (pharmacologic agents to protect the brain after stroke and trauma), Tristram Smith, PhD (behavioral interventions for autism spectrum disorder), Susan Hyman, MD (diet and nutrition in autism spectrum disorder), and Krystel Huxlin, PhD (retraining the brain to see after stroke), to name just a few.
The SMD’s Department of Neuroscience (formerly the Department of Neurobiology and Anatomy) now chaired by Foxe, has roots dating to 1929, as one of the five original basic science departments of the school. It was first in the medical school to offer formalized graduate training leading to advanced degrees (MS and PhD).
Collaboration has always been the department’s hallmark. Former chair Carl Mason, MD, initiated ties with Orthopaedics and Neurosurgery, and former chair Wilbur Smith, MD, partnered with Pediatrics to provide fellowship training in Pediatric Neurology. It was former chair Carl Knigge, MD, who first steered the department’s focus toward the neural sciences (leading a national trend), a shift that was fully realized under former chair John Sladek, Jr., MD, who changed the department’s name to Neurobiology and Anatomy in 1985. Over the years, Neuroscience nurtured its close ties with clinical disciplines, reflected in the large number of students who complete the department’s medical and graduate training.
The Department of Neurology, chaired by Bob Holloway, MD (Res ’93, MPH ’96), ranks 10th in NIH funding. Neurology, Neurosurgery and Neuroscience are currently responsible for 25% of the Medical Center’s research, making URMC a hub for global research networks conducting multi-center clinical trials. And clinically, Neurology and the Department of Neurosurgery, chaired by Webster Pilcher (MD/PhD ’83, Res ’89), are ranked among the best programs in the country by U.S. News and World Report, with Strong Hospital noted for the most advanced brain and spinal surgical program in the state.
The team research initiative Foxe is spearheading as director of The Del Monte Institute taps the scientific prowess of all of these departments, and extends to include researchers in the departments of Psychiatry, Pharmacology & Physiology, Otolaryngology and other specialties. But it also reaches further to draw upon the brainpower across the UR’s River Campus, within the School of Nursing, the Eastman Institute for Oral Health and Warner School of Education.
“World class neuroscience is woven into the fabric of the University, with basic and translational investigators working across more than a dozen departments and centers,” says Foxe. In 2016 he led an exhaustive assessment of UR’s current team-based neuroscience programs, identifying 17 centers of excellence in the process.
"World class neuroscience is woven into the fabric of the University, with basic and translational investigators working across more than a dozen departments and centers."
One of the first in the nation to offer an undergraduate program in neuroscience, the University is now among the top institutions in the world for studying multisensory integration (how sight, sound, touch, smell and taste are integrated in the brain), and is home to pioneers in optics technology development and applications.
“Additionally, we have exceptional computer science and data analytics experts, amazing technological abilities to monitor brain activity, and one of the best biomedical engineering departments in the country,” says Foxe. “Very few universities possess this span and depth of expertise. It opens the door to developing new devices, new sensors and new ways to monitor and interface with humans. Our Center for Health and Technology then gives us a vehicle to get these technologies out the door and test their benefits in real-life situations. Pooling our abilities across the campus gives us a whole new vista to study multisensory integration.”
Basic science investigators also have the ability now to recapitulate a human disease in a mouse or rat model in a matter of weeks, rather than years, to test new antibodies and techniques. These genetic engineering capabilities have exploded in the last decade, “significantly advancing our ability to understand the underlying mechanisms of neurologic diseases,” he says.
A more subtle but equally important advantage is Rochester’s culture, says Foxe.
“Having worked in big-city institutions, Rochester is friendlier and people talk more readily. We also have geography on our side. The undergraduate campus is nested against the graduate campus and Medical Center, with the Rochester Center for Brain Imaging (RCBI) in the middle as a fulcrum. It’s very easy to go back and forth, which isn’t the case at most places.”
Of course, a crucial element is that University leaders believe in the effort’s value.
Kerry O'Banion, M.D., Ph.D., and M.D./Ph.D. student Dawling Dionisio-Santos work in O'Banion's lab. Their team explores the role of neuro-inflammation in Alzheimer's disease, and conducts related studies on radiation's effects on the brain.
“The folks at the top of the chain here get it,” he says. “The philosophy of bigger team-led science is being supported in the president’s office, and in the dean’s office. That makes it easier for me to do my job. They’ve made a massive investment in renovation and creating new space for us, and to free up resources the labs need to work at the team level.”
Vice chair of Neuroscience Kerry O’Banion, MD, PhD, who was tapped by Foxe to lead the effort to synergize research on Alzheimer’s and dementia-related diseases, says it helped to have “someone from the outside to pull people out of their comfort zones and stir things up. John’s good at doing that, and at the same time advocating for what researchers need. He also realizes that what really matters to scientists is to be a part of building something super-cool.”
Setting the Pace
Transforming an entire research program might seem a huge feat for a self-described former “dumb jock” who didn’t take his first science course until his 20s. But Foxe—who grew up running the craggy coastal roads of Dublin and posted sub 1:50 minute half-mile times in college—has a habit of making marathons look like sprints.
His athletic talent earned him a scholarship to Iona College, where he took “bits and bobs” of courses to maintain NCAA eligibility, eventually earning a degree in Psychology.
“Science wasn’t even on my radar,” he says.
But in his senior year, one of his professors—a devoted track and field fan—persuaded Foxe to take a physiological psychology course, which “blew my mind” and sold him on pursuing a career in the field.
However, with no science training, he was advised to find a job as a lab technician. After knocking on dozens of doors, one professor took a chance on him—David Stapells, MD, at Einstein College, who was using electrophysiology to record brainstem responses in preemies.
“The first time I saw the recording of brain activity of a baby born as early as 15 weeks premature, I was completely hooked,” says Foxe, who published his first paper with Stapells. “I found it extraordinary that you could track how an auditory stimulus propagated through the brain of a tiny infant, and learn meaningful things about the health of their neural architecture. I was floored by it, and still am 25 years later. I find that same excitement in knowing we can literally watch the inter-workings of the human mind.”
When Foxe applied to Einstein for grad school, he was admitted provisionally, and had to scurry to complete a hefty slate of undergrad science courses in a 10-week summer session to start in the fall. There, he was inspired by, and collaborated with, neuroscience professor Steve Walkley, PhD, who later recruited Foxe to teach the medical school’s neuroscience course for 12 years. Meanwhile Foxe also worked seven years at CUNY, directing the PhD program in cognitive neuroscience and co-directing its children’s research unit. He also led the Cognitive Neurophysiology Laboratory at the Nathan S. Kline Institute for Psychiatric Research.
Then in 2010, he was recruited to create and direct a new clinical pediatric research initiative within Einstein’s Children’s Evaluation and Rehabilitation Center (CERC), one of the largest U.S. clinics that evaluates, diagnoses and treats children and adolescents with autism, ADHD, cerebral palsy and hearing impairments. Foxe engaged basic science researchers from across the institution to assist CERC clinical researchers in investigating the genetic, neurologic, physiologic and environmental causes of these conditions. What emerged was a high-tech, multi-methodological lab where basic science projects of healthy individuals are conducted in tandem with clinical studies of affected populations to develop novel assays.
Foxe—whose efforts paid off in restoring the CERC’s top-tier NIH funding it had lost a decade earlier—wants to replicate what he did at Einstein on a much grander scale in Rochester.
What drives him is the same enthusiasm he had when he watched those first brainstem recordings of neonates. But there is also a renewed sense of urgency.
“I get impatient when I think about how many people are suffering…waiting for cures. But I also have a relentlessly optimistic view of things. I know we can create something truly special here. I just try to move the goalposts a little bit every day, even if it’s an inch at a time.”