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Johns Hopkins Medicine
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Eric Vohr
  Joanna Downer

  -- Two Nobel laureates among guest speakers; Solomon Snyder honored

The Johns Hopkins University School of Medicine celebrated its sterling track record in brain sciences at a pioneer-rich symposium Nov. 11 in the Thomas B. Turner Auditorium on the school’s East Baltimore campus.

The event marked the 25th anniversary of the founding of the Department of Neuroscience at Johns Hopkins by Solomon H. Snyder, M.D., and his leadership of the department, along with the contributions of the departments of Psychiatry, Neurosurgery and Neurology, which is celebrating its 35th anniversary.

Speakers at the symposium were Nobel laureates Richard Axel and Eric Kandel and fellow neuroscientists Cornelia Bargmann, Roger Nicoll, Carla Shatz, William Newsome III, Fred Gage and Huda Zoghbi. Hopkins neuroscientists Rick Huganir and Snyder opened and closed the symposium, respectively, which served as a prelude to the start of the annual meeting of the Society for Neuroscience Nov. 12 in Washington, D.C.

Guest speakers described their research advances -- from understanding smell and vision, to probing the science of memory and decision-making, to investigating how new brain cells work, to revealing the problems behind balance-destroying diseases called spinocerebellar ataxias.

But beyond the symposium’s brainpower, there’s a lot of neuroscience happening at Hopkins, whose faculty contributions deliver both context and background to the symposium’s theme of “Discovery and Hope.”

Each of the four brain sciences departments is described in the “primer” below, and a few researchers in each are briefly profiled.

The Department of Neuroscience officially came into being on July 1, 1980, with Solomon Snyder, M.D., in charge. For 25 years, Snyder has led the department and shaped its growth. He’s stepping down as director this year, which is part of the impetus for the celebration.

For years earlier, Hopkins boasted plenty of neurophysiologists -- Snyder, Vernon Mountcastle, David Hubel, Joseph Coyle, David Robinson and many others -- and neuroanatomists -- David Bodian, for one -- scattered among various departments. The department's founding offered the chance to formalize the basic science effort and to grow.

In the mid 1980s, the Howard Hughes Medical Institute selected Johns Hopkins as one of four sites for the new HHMI Neuroscience Institute. In 1986, Snyder and other faculty advisers recruited the first three HHMI neuroscience investigators to Hopkins and added two more investigators whose primary appointments were in the Department of Molecular Biology and Genetics. In subsequent years, neuroscience faculty already at Hopkins were eligible to become HHMI investigators within the Neuroscience Institute.

The Department of Neuroscience is the largest of the eight basic science departments at the Johns Hopkins School of Medicine, and includes the Zanvyl Krieger Mind/Brain Institute located on The Johns Hopkins University’s Homewood campus. The department’s faculty, including those whose primary appointments are in other departments, investigate brain cells and nerves on a cellular and molecular level, study the cues that control their development, probe the underpinnings of diseases affecting the brain, and delve into cognition and behavior and ways to model those abilities on computers. The work of a few neuroscience faculty members is described below.

Sol Snyder, M.D.
Snyder’s lab was the first to isolate and identify brain cells’ docking points for opiates as well as to uncover the brain’s own opiates. For this work, Snyder received the Albert Lasker Award in 1978. In more recent years, Snyder's laboratory has uncovered new neurotransmitters -- molecules that brain cells use to communicate with one another -- including nitric oxide and carbon monoxide, proving that gases can act as neurotransmitters, too.

His lab has also discovered that the tiny yellow molecule bilirubin, known well as the culprit behind jaundice, is part of a potent and natural process to detoxify dangerous, highly reactive oxidants.

Just this year, he and his colleagues reported that a strange molecule laden with phosphate groups actually transfers phosphates onto proteins, a role previously known only to belong to a well-studied molecule called ATP. ATP and the molecule Snyder's lab identified, known as IP7, turn proteins “on” and “off” by adding phosphates to them.

Rick Huganir, Ph.D.
Rick Huganir, professor of neuroscience, studies the basis of learning and memory, probing how brain cells form connections and communicate with each other. Central to investigations in his laboratory and a few others at Hopkins are the molecular details of two processes: one that prevents one brain cell from reacting to messages from another, and one that maintains the reaction when the stimulating trigger is no longer there.

Among his achievements are the engineering of a forgetful mouse, work done with the laboratory of Michela Gallagher, Ph.D., professor of psychological and brain sciences in the Krieger School of Arts and Sciences at The Johns Hopkins University.

Alex Kolodkin, Ph.D., and David Ginty, Ph.D.
In the laboratories of Alex Kolodkin and David Ginty, both Howard Hughes Medical Institute investigators and professors in the Department of Neuroscience, researchers are identifying and studying the molecular signals that guide nerves’ growth during development and enable their connections to correct targets throughout the body.

As a postdoctoral fellow, Kolodkin led the discovery of the largest known family of these so-called guidance cues -- a group of proteins called semaphorins -- that, in general, repel the growing tip of nerves, keeping them from making a wrong turn.

Among other projects, collaborations between the Ginty and Kolodkin labs are probing exactly how these semaphorins, similar guidance cues and their cell surface receptors called neuropilins direct nerves to their appropriate targets and enable connections to be established. Ultimately, the researchers’ work in fruit flies and mice could help shed light on how to promote regrowth of human nerves damaged by injury or disease.

The Department of Neurology at Hopkins finds its roots in the turn of the 19th century, when Hopkins’ first neurologist, Henry Thomas, published widely on both peripheral and CNS aspects of unchecked syphilis -- the common neurological ill of the day. For year, attempts were made to put neurology on equal footing with psychiatry. But it wasn’t until 1967 that an official department was formed under chair Guy McKhann. McKhann instituted a research based agenda that uses the institution’s exceptional grounding in neuroscience to tackle neurological disease.

Richard Johnson, the next chair, continued in a similar vein, shoring up basic and clinical science and making the department a magnet for training clinician scientists.

Today, with John Griffin as head, the faculty has grown to 105 members. And advances continue to be made in critical fields, such as pediatric epilepsy, cognitive neuroscience, cerebrovascular medicine, neuroimaging, neuromuscular and neuroinfectious disease, neurointensive care and, more recently, neuroimmunology.

The work of a few of the neurology department’s faculty members is described below.

Ted Dawson M.D., PH.D.
Ted Dawson is responsible for many advances in the neurobiology of disease thanks to his participation in the identification of the mechanisms of brain cell death and neurodegeneration.

Dawson’s discoveries have led to innovative approaches and enhanced the development of new agents to treat neurologic disorders, such as, stroke, Parkinson’s disease and Alzheimer’s disease.

Dawson is the Leonard and Madlyn Abramson professor in neurodegenerative diseases, the director of the Neuroregeneration and Repair Program in the Institute for Cell Engineering and the director of the Parkinson’s disease and Movement Disorder Center at Hopkins.

Valina L. Dawson PH.D.
Valina Dawson’s lab is best known for its work studying the mechanism of injury that occurs following stroke. Her lab is actively researching which proteins are responsible for the brain protective properties associated with the phenomena of “preconditioning.”

Her lab also investigates gene mutations linked to Parkinson’s disease and how these mutations might contribute to the loss of brain cells. This work will hopefully lead researchers to new therapeutic opportunities.

Valina Dawson is the director of the Program in Neuroregeneration and Repair in the Institute for Cell Engineering and a vice-chairman of the Department of Neurology.

Valina Dawson was recently recognized by the ISI as one of the 100 most cited neuroscientists in the last decade.

Justin McArthur M.B.B.S., M.P.H.
Justin McArthur, acting chair of the Department of Neurology, has devoted his career to the investigation of the neurological manifestations of AIDS. For the past 20 years, he has been closely associated with the Johns Hopkins AIDS Service and initiated the HIV Neurology Consultation Program there.

As previous chair of the neurology committee of the AIDS Clinical Trials Group, he has been involved in numerous clinical trials of agents for HIV-associated neurological diseases. In addition, McArthur has developed a cutaneous nerve laboratory at Hopkins to better understand how diseases of the nervous system are linked to HIV.

McArthur also serves as co-chair of the American Neurology Association’s Long Range Planning Committee.

Jeffrey D. Rothstein M.D., Ph.D.
Jeffrey Rothstein studies neuromuscular diseases such as amyotrophic lateral sclerosis (ALS), epilepsy, spinocerebellar ataxia.

His lab recently discovered that beta lactam antibiotics have the ability to activate brain genes to turn on production of glutamate transporters – a known therapeutic target for treating neuromuscular diseases. In collaboration with the National Institutes of Health (NIH), his group is now screening more than 100,000 chemicals to identify effective drug therapies.

Rothstein organized the Robert Packard Center for ALS Research at Johns Hopkins and serves as medical director. This is the first multi-institutional, multinational collaborative academic organization devoted to understanding the cause of ALS and translating the information into new drug therapies.

Rothstein is also the co-director of the Muscular Dystrophy Association/Amyotrophic Lateral Sclerosis (MDA/ALS) Clinic, and vice chairman for research in the Department of Neurology.

Neurosurgery’s offerings to brain science at Hopkins begin with the noted neurosurgeons Harvey Cushing and Walter Dandy, who, even before the 1920s, had grounded that specialty in research. They not only lowered brain surgery mortality to less than 10 percent, but also advanced the idea of neurosurgeons as scientists.  Though their studies were largely clinical, their targeted studies of brain anatomy and physiology paved the way for research to come.

In 1946, Earl Walker succeeded Dandy as director of the Division of Neurosurgery and carried on work in research. His focus was epilepsy -- its origins, its various forms and its effects on brain physiology -- as well as the surgery, making Hopkins a center of national repute.

When Donlin Long signed on at Hopkins in 1973, he made sure it was to head a proper Department of Neurosurgery, not a division. During his watch, Long set up formal subspecialties within the department as well as “centers of excellence” that uniquely crossed disciplines to investigate specific problems.

In 1987, neurosurgeon Henry Brem continued the spirit of research-based medicine pioneered by Cushing and Dandy with a bench to bedside emphasis on brain tumor therapy.

Today, three of the 31 faculty in the department have won the Grass Foundation Award, the top prize for neurosurgeons doing research.

The work of a few of the neurosurgery department’s faculty members is described below.

Fred Lenz, M.D.
Fred Lenz, director of functional neurosurgery, has revolutionized the understanding of human thalamic organization and been involved in the introduction of new treatments for movement disorders. Lenz continues to show how the thalamus and cerebral cortex relay and interpret sensory and motor information.

His work has revealed that both chronic pain and movement disorders can reorganize the thalamic representation of the body -- the homunculus. His studies have also refined techniques used to make deep brain stimulation a viable option for patients with movement disorders like Parkinson’s disease.

Gregory Riggins, M.D., Ph.D.
Gregory Riggins’ research focuses on locating and analyzing molecular targets for brain cancer therapy. He also screens for small-molecule inhibitors of brain cancer mutations.

His lab has recently found that a neural developmental gene, OTX2, is amplified in many medulloblastoma -- the most common pediatric brain cancer.

His lab is also known for initiating and coordinating the SAGE Genie Website for the National Cancer Institute and the Cancer Genome Anatomy Project. This Website is the largest public expression database. It uses SAGE to quantify gene expression in most all genes expressed in over 250 different samples from cancers and normal tissues.

Riggins is the first recipient of the Irving J. Sherman Research Professorship in Neurosurgery Research.

Rafael Tamargo, M.D.
Rafael Tamargo, current director of cerebrovascular neurosurgery, has done extensive research into the molecular mechanisms of vasospasm -- the narrowing of the arteries within the brain after stroke -- and established that inflammation is the root cause for this problem. Along with Richard Clatterbuck, Tamargo has introduced new and promising controlled-release polymers with nitric oxide for treatment of vasospasm. In addition, Tamargo has expanded the surgical approaches to aneurysms.

Psychiatry began at Hopkins just after the turn of the 20th century, in an atmosphere slightly out of sync with the rest of the country. Whereas Freudian psychoanalysis was widely accepted and practiced in America, Adolph Meyer, “the dean of American psychiatry,” and the department’s first director, preferred a broader, more utilitarian approach to mental illness.

Meyer’s psychobiology espoused a holistic view of patients, one that took in all aspects of their lives -- including the physical -- to reach them at a psychological level. Among other things, his approach brought a new way to assess patients, the psychiatric workup that became a Hopkins hallmark and the cornerstone of what’s used today worldwide.

During Meyer’s directorship, and that of successor John Whitehorn, 1941 1960, efforts centered on defining psychiatric disease and the psychiatrist/patient relationship. Under director Joel Elkes, 1965 1973, who encouraged forays into the new field of psychopharmacology, Sol Snyder began his meteoric career in molecular neuroscience, and Joe Brady became a figure in landmark studies in behavioral neuroscience.

But it was under Paul McHugh, 1975 1998, that brain based science at Hopkins bloomed. Under his watch, the departmental research portfolio grew from about $1 million to $30 million. A clinician scientist by training and a man of conviction by anyone’s standards, McHugh saw a firm grounding in science as psychiatry’s best hope.

Today, director J. Raymond DePaulo maintains the drive to understand the biology of psychiatric illness. He’s broadened support of underlying molecular biology, genetics and even neuroanatomy -- via the newest neuroimaging, for example -- while simultaneously encouraging direct interaction with patients.

The work of a few of the psychiatry department’s faculty members is described below.

Adam Kaplin, M.D., Ph.D.
Adam Kaplin’s specialty is psychiatric complications of neurological diseases. His research has focused on mechanisms of neuronal stimulation, communication and injury. He currently focuses on immune-mediated mechanisms of depression and cognitive impairment in Transverse myelitis, multiple sclerosis and related autoimmune neurologic disorders, and the role of chemical messengers, called cytokines, in these processes.

Since 1999, Kaplin has served as the chief psychiatric consultant to the transverse myelitis and multiple sclerosis centers at Hopkins. He is an integral collaborator for the clinical and research endeavors of these centers, with an expertise in investigating the biological basis of autoimmune effects on mood regulation and cognition, and the care of patients afflicted with these complications. Kaplin is on the board of medical advisors to the Transverse Myelitis Association and the Montel Williams MS Foundation.

Constantine Lyketsos, M.D.
Constantine Lyketsos heads the Johns Hopkins Memory Center and co-directs its geriatric psychiatry and neuropsychiatry division. Lyketsos has shaped the center into this country’s number one site for dementia diagnosis and care, especially for Alzheimer’s disease.

In his research, he has worked to show that dementia is more than losing thinking ability and memory; it goes hand in hand with depression, delusions and agitation. More recently, Lyketsos has suggested that prompt, aggressive therapy for depression and other non memory symptoms may slow the fall into full-blown dementia. He’s presently testing that idea while fostering a deeper look into the biology of dementia in the hope of developing better treatments. The latter’s especially crucial, given the huge number of baby boomers who will soon stretch psychiatry’s resources.

Jennifer Payne. M.D.
Jennifer Payne has made a career out of studying gender differences in mood disorders and has helped establish a new Hopkins clinic dedicated to treating mood disorders in women.

Payne has discovered that the trait of being sensitive to hormonal change seems to run in some families whose members have been known to suffer with major depression and may therefore have a genetic basis. 

Her recent work, for example, suggests that postpartum depression runs in families, which led her to look at genes turned on or off by estrogen. One of the focuses of her study is the gene for BDNF, a nerve-stimulating molecule newly tied to bipolar disorder.

Sarah Reading, M.D.
Sarah Reading is a psychiatrist using advanced MRI techniques to better understand the relationship of brain structure and brain function in patients with schizophrenia, bipolar disorder and Huntington’s disease.

Her current projects utilize functional MRI (to study brain activity) and diffusion tensor imaging (to study neural circuitry) during specific tasks of cognitive function.

Reading is a recipient of a Johns Hopkins University Clinician Scientist Award
and a recipient of the Johns Hopkins Hatten S.Yoder III Memorial Fellowship for research in schizophrenia.

Christopher Ross, M.D., Ph.D.
Christopher Ross has made great advances in the study of how genes cause neuropsychiatric disorders. His team is using cellular and molecular approaches to study the pathogenesis of Huntington’s disease, Parkinson’s disease, other neurodegenerative disorders, and psychiatric disorders such as schizophrenia.  

They have discovered genetic mutations underlying several diseases and are identifying novel genes as candidates for diseases whose causes are currently unknown. They have developed cell and mouse models of neurodegenerative diseases and schizophrenia, which they are using to test for novel therapeutics.

Akira Sawa M.D., Ph. D.
Akira Sawa heads a research team whose focus is to better understand the pathogenesis of psychiatric illnesses, especially schizophrenia, at the molecular level.

Recent advances in neuroscience suggest that schizophrenia is a brain disorder stemming from an abnormal origin of neurodevelopment, resulting in a disturbance of some neurotransmitter systems. These advances have led Sawa’s team to study some of the genes potentially involved in schizophrenia, including DISC-1 (disrupted-in schizophrenia). DISC-1 was identified as a disrupted gene in a large Scottish family with major mental illnesses such as schizophrenia.

His team also reported that a cancer gene might have a role in neurodegenerative conditions like Huntington’s disease. In addition, they discovered a novel function of the enzyme glyceraldehyde-3-phosphate dehydrogenase in cell death.