Dr. Robert H. Brown, Jr.

 

 

Dr. Robert H. Brown

Dr. Robert H. Brown, Jr.

Robert H. Brown Jr., DPhil, MD, the Leo P. and Theresa M. LaChance Chair in Medical Research and chair of the Department of Neurology at the University of Massachusetts Medical School (UMMS) and UMass Memorial Medical Center, is an internationally known researcher and physician leading the quest to cure neurodegenerative and neuromuscular diseases like amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease.

Renowned for his groundbreaking basic and clinical research on the inherited and genetic basis of neurodegenerative and neuromuscular diseases, Dr. Brown has a record of significant discoveries in identifying gene defects that elucidate how ALS causes neurons to die. In 1993, a team of researchers led by Dr. Brown discovered the first gene linked to the inherited form of ALS, called SOD1.

Each year, it is estimated that 5,000 people in the United States are newly diagnosed with ALS, a progressive, neurodegenerative disorder affecting the motor neurons in the central nervous system. As motor neurons die, the brain’s ability to send signals to the body’s muscles is compromised, leading to the loss of voluntary muscle movement, paralysis and eventually death from respiratory failure. The average survival rate for patients with ALS is three to five years.

ALS is a fundamentally untreatable disease, and its cause is still not entirely understood. About 10 percent of ALS cases arise because of inherited genetic defects. The cause of the remaining 90 percent of cases, known as sporadic ALS, is still unknown. One hypothesis is that in these cases, the disease is triggered by a combination of genetic susceptibility and exposure to one or more adverse environmental factors. For example, there is growing evidence that head trauma may predispose patients to ALS and related cognitive decline.

Development of new therapeutics to treat ALS depends on better understanding how the disease works. In October 2010, Brown and his team at the University of Massachusetts Medical School reported evidence suggesting that the SOD1 gene, which is implicated in 20 percent of inherited cases of familial ALS, also plays a part in the more common, sporadic forms of the disease. Brown’s research showed that under certain conditions and absent a mutation in the gene, a normal SOD1 protein can have the same toxic characteristics that are found in mutated forms of the gene. In select cases of sporadic ALS, these toxic proteins are present.

When he began researching ALS over 20 years ago, Brown believed that one day his work to identify the genes implicated in the inherited form of ALS would yield new insights into the more common, sporadic form of the disease. These findings are the first evidence that genes implicated in inherited ALS also play a role in the sporadic form of the disease.

Dr. Brown joined the University of Massachusetts Medical School as chair of neurology in May 2008, in part, because of the work of its internationally known scientists unraveling the mechanisms that turn genes on and off. UMMS is home to some of the world’s leading researchers in the field of RNA biology (RNA interference or “RNAi,” is a gene-silencing mechanism for which UMMS Professor Craig C. Mello shared the Nobel Prize in Physiology or Medicine in 2006), which Dr. Brown believes holds immense potential as a therapeutic for neurodegenerative diseases such as ALS, with its ability to create and regulate the complex patterns of gene expression. Initiated by Dr. Brown, an ALS-related arm of these efforts includes a program to silence the activity of mutant ALS genes that make the toxic proteins that trigger the disease. Working in conjunction with researchers at the Gene Therapy Center at UMMS, Dr. Brown is accelerating efforts to devise novel gene therapies that can access the brain and spinal cord for diseases such as ALS.

Shortly after joining UMMS, Brown and his colleagues identified a new genetic mutation linked to ALS which is estimated to account for 5 to 10 percent of inherited cases. Discovery of this mutation, called FUS/TLS, was named one of the most cited papers from 2008 to 2010 by Thomson Reuters. Though it’s still not clear how the FUS/TLS mutation causes ALS, scientists know that the FUS/TLS protein plays a number of roles in the neuron cell. In healthy neuron cells, the FUS/TLS protein is located predominately in the cell nucleus. Samples from patients with the FUS/TLS mutation show a concentration of the FUS/TLS protein in the cytoplasm of the cell, however, outside of the nucleus. This misplaced protein is believed to contribute to cell death in neurons.

Brown has also identified disease genes in other inherited neurodegenerative and neuromuscular diseases such as hyperkalemic periodic paralysis, Miyoshi muscular dystrophy and hereditary sensory neuropathy.

Dr. Brown and his team have been very fortunate to receive support from a diversity of groups, including the locally-based organization, Angel Fund, and national partner, CVS Pharmacy, both of which have been raising money for ALS research for more than 10 years.

Outside of the lab, Dr. Brown is known as a compassionate clinician and physician, caring for patients suffering from neurodegenerative diseases. He is well known for his work with patient advocacy groups and charitable organizations.

Dr. Brown has received many honors for his extraordinary commitment to finding cures for neuromuscular diseases, including induction into the Institute of Medicine. He was also the recipient of the National A.L.S. Foundation Fellowship from 1980 to 1982, Plenary Lecturer at the American Academy of Neurology in 2002 and 2007, and is a member of the American Neurological Association. In 2011 he was named a member of the Association of American Physicians (AAP).

Dr. Brown graduated from Amherst College with a degree in biophysics in 1969. He went on to complete a doctorate of philosophy in neurophysiology at Oxford University and received his medical degree from Harvard Medical School in 1975. Following medical school, Dr. Brown completed his internship in internal medicine at Peter Brent Brigham Hospital and his residence in neurology at Massachusetts General Hospital. In 1983, Dr. Brown completed a research fellowship in neuroscience at Children’s Hospital in Boston.

In 1975, Brown joined Harvard Medical School as a clinical fellow and rose to the rank of professor of neurology in 1998, while also serving as Director of the Day Neuromuscular Laboratory and of the Muscular Dystrophy Association Clinic. Internationally recognized for its research and clinical care programs, Brown founded the Day Neuromuscular Laboratory in 1984 to investigate neuromuscular diseases. Dr. Brown continues his work with the Day Neuromuscular Laboratory today at the University of Massachusetts Medical School.

WORCESTER — Robert H. Brown Jr., MD, DPhil, an internationally known researcher and physician who has led the quest to cure neuromuscular diseases like ALS, has accepted the appointment of chair of the Department of Neurology at the University of Massachusetts Medical School and UMass Memorial Medical Center.

“This appointment has the potential to be truly transformational to our clinical and research missions and has broad institutional implications,” says Terence R. Flotte, MD, executive deputy chancellor, provost and dean at UMMS. “Dr. Brown’s outstanding international stature and vision, which bridge translational research and clinical care, are emblematic of how our academic health sciences center is capitalizing on the life sciences moment in Massachusetts.”

Brown comes to UMass Medical School and UMass Memorial Medical Center from Harvard Medical School and Massachusetts General Hospital, where he has been Professor of Neurology and Director of the Day Neuromuscular Laboratory and of the Muscular Dystrophy Association Clinic. Brown founded the Day Laboratory in 1984 to investigate neuromuscular diseases, and it has become internationally recognized for its research and clinical care programs. Brown is renowned for his work on the inherited basis of neurodegenerative and neuromuscular diseases and has a record of significant discoveries in amyotrophic lateral sclerosis (ALS) and neuromuscular disorders, including some types of muscular dystrophy. He will join UMMS and UMass Memorial in October.

In 1993, Dr. Brown and colleagues defined mutations in a gene as one cause of familial ALS. He has already collaborated with UMass Medical School Professor of Biochemistry & Molecular Pharmacology Zuoshang Xu, MD, PhD, in his work to develop an RNA interference-based approach that may herald a treatment for certain neurodegenerative diseases. (RNA interference, or “RNAi,” is a gene-silencing mechanism for which UMMS Professor Craig C. Mello shared the Nobel Prize in Physiology or Medicine in 2006.)

“I am thrilled that Bob Brown has chosen to bring his research group to UMass Medical School,” said Dr. Mello. “In addition to being a truly outstanding scientist who has made seminal discoveries relating to the genetics of neurodegenerative disease, Bob is one of the most dedicated physicians I have ever met. Having identified the genetic basis for familial ALS, he could simply wait for others to develop therapies based on his discoveries. But Bob knows that his patients don’t have the luxury of time. He comes to UMMS and UMass Memorial with one clear purpose in mind, to develop advanced therapies for ALS and other devastating diseases. We are honored to welcome Dr. Brown and his colleagues to this community and we are eager to redouble our own efforts to further his important work.” Brown graduated from Amherst College, Harvard Medical School and Oxford University, where he received a doctorate in neurophysiology. He has received many honors for his extraordinary commitment to finding cures for neuromuscular diseases, including induction into the Institute of Medicine.

“The appointment of Bob Brown ushers in an exciting new era in translational medicine at the University of Massachusetts Medical School,” said Michael F. Collins, MD, interim chancellor. “His work as a physician and a researcher has had a major impact in the field of neurology, so the opportunities for advancing research and treatment by joining this scientific community are immense. The University of Massachusetts Medical School is at the center of a revolution in the life sciences, and leaders like Dr. Brown are a key reason why we’ll be successful.”

“Dr. Brown’s extraordinary experience as a clinician and leading researcher at a prominent academic medical center makes him a superb choice for this position,” said John G. O’Brien, president and chief executive officer of UMass Memorial Health Care. “UMass Memorial, in addition to providing great patient care, is poised to be a leader in clinical research, and Dr. Brown is extremely enthusiastic about the opportunities awaiting him here. This is an important moment in the history of this institution.”