Previous Fellows

Previous Massachusetts General Hospital Fellows

2011 | 2010 | 2009 | 2008 | 2007 | 2006 | 2004 | 2003 | 2002 | 2001 | 2000 |

Nicte Mejia-Gonzalez, MD, 2011 Rappaport Research Scholar

 

Nicte Mejia's research seeks to improve clinical outcomes for patients with chronic neurologic conditions such as Parkinson disease.  She particularly focuses on addressing the impact of racial and socioeconomic factors on neurologic care and outcomes.  Funding from the American Academy of Neurology is allowing her to merge her movement disorders clinical research career with neuroepidemiology projects to address possible health disparities.  Her study, Race/Ethnicity and Access to Deep Brain Stimulation among Parkinson Disease Patients, was just selected for a Scientific Session platform presentation at the upcoming American Academy of Neurology annual meeting.  Using ten years of a U.S.-wide dataset, she evaluated the effect of race and ethnicity on access to deep brain stimulation for Parkinson disease patients.  She documented that Black and Hispanic/Latino Parkinson disease patients were significantly less likely than Whites to receive deep brain stimulation in the U.S. between 1998-2007.  This disparity in odds of receiving deep brain stimulation was not accounted for by adjusting for age, sex, socioeconomic status, hospital-specific characteristics, or geography: OR=0.09 (CI 0.06-0.14) for Blacks and OR=0.73 (CI 0.61-0.87) for Hispanic/Latinos when compared to White patients.  She plans to replicate these research findings using a different dataset that includes greater clinical detail, apply qualitative research methods to better understand this disparity, and propose targeted interventions to close this treatment gap.

Nicte became an Instructor in Neurology at Harvard Medical School and Assistant in Neurology at MGH in July of 2010.  She has blossomed since transitioning from fellowship training to her new academic position, as others in our field learn about her research focus.  She actively collaborates with researchers across medical disciplines at MGH and other institutions on projects related to neurologic health equity.  The journal Neurology invited her to write an editorial published in late 2010, which will have longstanding impact on how neurologists perceive and address racial and social disparities.  She has given Grand Rounds on the impact of racial and social factors on stroke care for the TeleStroke network.  Nicte has also successfully mentored two Harvard Medical School students who are underrepresented in medicine towards receiving scholarships to attend the upcoming American Academy of Neurology annual meeting.  She is active at an institutional and national level in committees that pertain to neurologic education, clinical research training, and workforce diversity.  She also participates in community outreach activities including speaking to underrepresented students who visit MGH on pursuing scientific and medical careers.

Dr. Mejia plans to further develop her clinical research initiatives through local and U.S.-wide collaborative studies on access to neurologic care and clinical outcomes. She plans to obtain K, and subsequently R01, funding to solidify her neurologic health equity and clinical outcomes research activities.  She hopes to extend her academic endeavors internationally within five years of becoming faculty, especially by collaborating with clinical researchers in developing areas of the world.  Her ten year plan is to: 1) become a well established, productive, and innovative clinical researcher with neurologic clinical outcomes and health equity research collaborations globally; 2) lead initiatives aimed to improve patients' access to quality neurologic care; and 3) be an active educator and mentor on neurologic outcomes and health equity research.

Mireya Nadal-Vicens, MD, PhD, 2010 Rappaport Research Scholar

Mireya Nadal-Vicens, MD, PhD is rigorously trained in basic laboratory science in the field of brain development. Her research and training plan relates to establishing a new model for depression and social defeat, and in this work she draws from several disciplines and departments at MGH/Harvard, including psychiatry, neuroscience, pharmacology, and genetics.

Mireya earned a BA from Harvard College, an MS in Neuroscience from Stanford University, and a PhD in the Department of Neuroscience at Harvard Medical School. During her PhD thesis work, Mireya studied the molecular signaling cascade responsible for the generation of neurons and glial cells during early brain development, working with newly discovered neural stem cells.  From her graduate work, Mireya co-authored a paper in Cell and two publications in Science.  She has been a Howard Hughes funded junior investigator and her graduate research was well-received and covered in the popular press.   

Mireya’s current work focuses on developing a new animal model of depression for the purpose of novel drug development.  As you know, depression is a chronic and often disabling disorder that is responsible for an enormous burden of suffering and economic cost.  Of note, is that virtually all of the medications in our arsenal for the treatment of depression are based on a few biological mechanisms that have been known for the past 40 years.  Though the number of drugs marketed for psychiatric disorders has increased dramatically over the past several decades, the number of truly novel molecular mechanisms has been stagnant.  In order to pursue this research, Mireya is collaborating and working with researchers in a variety of fields, including genetics, neuroscience, pharmacology, and drug development.  Mireya has been conducting her current research under the shared mentorship of Jordan W. Smoller, MD, ScD, an Assistant Vice Chair for Research in the Department of Psychiatry, and Dr. Edward Kravitz, the George Packard Berry Professor of Neurobiology at Harvard Medical School.  Mireya is a member of the Psychiatric Genetics Program in Mood and Anxiety Disorders, directed by Jordan Smoller, as well as a co-Investigator and member of the Center for Anxiety and Traumatic Stress Disorders, directed by Dr. Mark Pollack.  In addition, Mireya has begun to establish collaborations with researchers in the Center for Human Genetics Research, as well as establishing contacts with the Broad Institute, a multidisciplinary institute that spans MIT, Harvard and its affiliated hospitals.  These interdisciplinary efforts in Mireya’s research work are vital for the success of her research and are consistent with a new mission for collaborative research across Harvard and our hospital departments.

The fundamental hypothesis of Mireya’s work is that a novel, simple model of depression, brought about by adverse social interactions, can serve as a platform to test compounds to identify new drug/medication candidates capable of preventing depression-like behavior.  This model may reveal basic elements of how stress and genes interact to produce key features of mood disorders including depression, aggression, and helplessness. The model is based on the phenomenon of “social defeat” which has been shown in mouse studies to capture key biological elements of human depression and resilience.  The power of this model is the finding that social conflicts are particularly effective at inducing features of depression.  Her model extends this phenomenon of social defeat to a simpler model system—the fruit fly, Drosophila melanogaster.  The biology of Drosophila has been studied in exquisite molecular and genetic detail over the past one hundred years.  Thus, she can leverage the many sophisticated genetic tools that already exist to study this system.  Male fruit flies can reliably be induced to fight over limited resources and will do so instinctively in their very first social encounter, with one fly going on to win and the other abandoning the arena. The experience of losing changes the defeated fly in a profound and long-lasting manner.  After a single fight, the defeated fly will virtually never go on to win a subsequent encounter, even when they are more experienced than their subsequent opponents.  Losing an encounter seems to bias their future actions toward repeated defeat, even though they seem perfectly capable of fighting appropriately.  It appears that a switch has been thrown, and a single defeat defines their future behavior.

Mireya is working to discover the molecular components of this switch mechanism, to uncover how social conflict changes the brain.  The system she is perfecting is simple enough that this is a feasible and realistic goal.  With a molecular switch in hand, she can use it to screen an array of compounds to identify novel pharmaceutical agents.  This may lead to entirely new avenues of treatment for mood disorders.  It is her goal to progress from understanding in molecular detail how adversity changes the brain, to developing novel treatments based on those discoveries.

Mireya has presented her research at national meetings and she has been invited to publish her findings in a well-respected journal.  She is in the process of preparing a manuscript describing her social defeat paradigm and the novel and unexpected effects of current psychiatric medications on this behavioral assay (lithium leads to increased resilience whereas depakote leads to the stabilization of an initial winner/loser phenotype).  Meanwhile, Mireya has also been a co-investigator on a number of human trials in both bipolar and anxiety disorders.  She is preparing to conduct research in a translational way (using her invertebrate model to test candidate genes identified in human studies, while also preparing to conduct human trials on candidate genes identified in invertebrate systems).  This attribute makes her a powerful force for research in psychiatric neuroscience.

Mark W. Albers, MD, PhD, 2008 Rappaport Research Scholar

The focus of Dr. Albers’ laboratory is to gain a mechanistic understanding of early pathogenic processes of neurodegenerative diseases that are modifiable or reversible. Using mouse genetics, his lab has specifically tailored olfactory neurons to express disease genes associated with Alzheimer’s disease in a reversible manner, such that the disease gene can be turned off by feeding the mice a low-dose antibiotic. Patients with Alzheimer’s disease and Parkinson’s disease suffer olfactory deficits early in the course of their disease, pointing to a particular susceptibility of this neural circuit to the pathogenesis of these diseases, and making the olfactory system a logical starting point. Moreover, the olfactory neural circuit is one of the best-understood neural circuits in the mammalian brain. Characterization of this mouse model has uncovered a novel action of an Alzheimer’s disease gene – expression of this gene in less than 1% of the primary olfactory neurons is sufficient to cause olfactory deficits in behavioral assays. Reversal of the disease gene expression affects a complete recovery of the behavioral deficit in adult mice.

The generous support from the Rappaport Family Fund afforded Dr. Albers’ team the opportunity to learn that olfactory neurons are dying at an accelerated rate when the disease gene is expressed. This is the first mouse neuron population shown to be susceptible to this disease gene. This advance has generated exciting studies that delve into the molecular mechanisms leading to accelerated neuronal death and to develop a system to screen for molecules that interfere with this neurodegenerative process. Insights gained from these studies may contribute to the development of an effective therapy for these devastating diseases. The funds provided by the Rappaport Family helped support investigator salaries and defrayed costs associated with laboratory work, ultimately facilitating this important research. Dr. Albers’ findings will be published as well as presented at two international meetings.

Giulia Fulci, PhD, Neurosurgery, 2007 Rappaport Research Scholar

The Rappaport Award has been of immeasurable support in allowing Dr. Fulci’s research and career to move forward. Her research focuses on increasing efficacy of oncolytic virotherapy for brain tumors through transient suppression of the host’s innate antiviral defense responses. Oncolytic virotherapy is performed with viruses that selectively replicate in and kill tumor cells. Thus, these viruses can generate a progeny that spreads through the tumor while sparing the surrounding normal tissue. This is an excellent means to deliver an anti-tumor agent to isolated malignant cells that infiltrate the normal brain and that cause rapid re-occurrence of the cancer after standard treatments. Dr. Fulci is currently establishing a new magnetic resonance imaging (MRI) technique that allows monitoring in brain tumor patients the presence of antiviral immune responses, the intratumoral spread of the virus and the tumor response to the treatment throughout the therapy.

In summary, Dr. Fulci is establishing a state-of-the-art diagnostic tool that can evaluate in a quantitative and non-invasive fashion all three parameters and therefore provide fundamental information about the progress of the treatment. Through the Rappaport Family Fund, Dr. Fulci has received the support needed to obtain preliminary data for a National Institutes of Health R21 grant application that was recently awarded. This grant established her as an independent researcher and allows her to pursue her scientific interests. Moreover, her results were recently accepted for a presentation at an international meeting on gene therapy. 

Mohammed R. Milad, PhD, Psychiatry,2007 Rappaport Research Scholar

Thus, the support from the Rappaport Family Fund has allowed 1) the initiation of an important line of research to help understand differences between men and women in learning not to fear, 2) the scientific development of a post-doctoral fellow, and 3) the scientific development of a junior faculty member in the department of psychiatry.

Eric M. Morrow, MD, PhD, Psychiatry, 2007 Rappaport Research Scholar

The Rappaport Award has provided important support for Dr. Morrow's research. Dr. Morrow’s research has focused on neurodevelopmental and genetic mechanisms that are root causes of childhood neuropsychiatric illness such as autism and related disorders of cognitive development.  During this year, Dr. Morrow has completed 3 projects which are now under review:  1) The first project involves using high-density SNP microarrays to identify loci in patients with autism from special founder populations. These patients were recruited as a part of the International Homozygosity Mapping Collaborative, an international genetics effort that Dr. Morrow co-directs. In this project, mutations in a gene were discovered in a subtype of autism involving comorbid seizure disorder. 2) In a second study, mutations in autism and mild mental retardation were discovered in a gene name alpha-neurexin-1.  3) In a third manuscript under review, Dr. Morrow conducted a mutational analysis of a gene involved in synapse remodeling in a patient cohort from the MGH Schizophrenia Research Program.

Dr. Morrow has applied the Rappaport Fellowship to salary support to provide protected time to complete studies, prepare manuscripts, and travel for international clinical research and national presentations.

Sydney S. Cash, MD, Neurology, 2007 Rappaport Research Scholar

Dr. Cash’s laboratory focuses on trying to understand normal and abnormal oscillations in the human brain. Specifically, he and his team are interested in understanding the mechanisms which underlie rhythmic activity in sleep, cognition and epilepsy. They use both non-invasive and invasive methods to study these phenomena and hope to use these results to improve diagnostic and therapeutic efforts to cure neurological disease.

With help from the Rappaport Family Fund, one of their most exciting research programs focuses on using specialized microelectrodes (shown here) to record from the human cortex and understand how seizures start, spread and stop. About 50 million people worldwide suffer from epilepsy – as many as 1/3 of these patients have seizures which can not be controlled with medications alone. Using these microelectrodes, Dr. Cash and his colleagues have recorded seizure activity in patients undergoing surgery for poorly controlled epilepsy. These studies offer a unique view of the physiology of seizures at a level of detail which has never been achieved in humans before. Early results are promising and suggest new ways to understand how seizures start and spread. Dr. Cash and his team hope to quickly expand on this new understanding and build new systems for detecting, predicting and controlling seizures.

William T. Curry, Jr, Neurosurgery, 2006 Rappaport Research Scholar

The Rappaport Award provided immeasurable support in allowing Dr. Curry’s research to move forward. His team is combining herpes virus treatment of malignant brain tumors with immunotherapy approaches in an attempt to generate more effective and durable strategies for this intractable disease. G47D is a herpes simplex virus type I that has been engineered in the laboratory selectively to replicate in, and, thereby, kill, dividing cancer cells. Normal brain tissue is essentially unaffected. Furthermore, the virus is further mutated so that it does not inhibit the generation of an immune response, and inflammation in the infected tumor is promoted. In mice, they have combined intratumoral injection of this potent virus with intratumoral injection of immature dendritic cells, which are generated by culturing bone marrow cells with particular cytokines. These dendritic cells can then process components of dying tumor and travel to lymph nodes where an antitumor immune response is generated. Their work has demonstrated that this combination viral and dendritic cell therapy is very effective, and, in fact, can cure most established subcutaneous tumors in mice. The researchers are currently working on this model in the intracranial compartment and are also combining oncolytic HSV-1 treatment of tumors with other immune modifiers.

The Rappaport funds provided for animals and reagents for these studies. With these data, Dr. Curry has achieved additional funding from the American Brain Tumor Association to continue this work. Two abstracts have been accepted for presentation at national scientific meetings.

Jonathan Rosand, Neurology, 2005 Rappaport Research Scholar

Dr. Rosand is Assistant Professor of Neurology at Harvard Medical School and Director of Fellowship Training in Vascular and Critical Care Neurology at MGH. His research in the prevention and treatment of hemorrhagic stroke focuses on identifying the genes that underlie the disease. He was recently recruited to the newly formed MGH Center for Human Genetic Research. The Rappaport Family Fund provided support at this crucial time to hire staff to assist Dr. Rosand in the establishment of an infrastructure for research in genetics. With this structure now in place, Dr. Rosand is able to initiate genetic studies independently and is in a much stronger position to apply for federal funds for his research.

Daphne Holt, Psychiatry, 2004 Rappaport Research Scholar

The crucial support of the Rappaport Family Fund has allowed Dr. Holt to complete her studies in the field of schizophrenia functional neuroimaging. Completing and publishing the results of these studies will allow her to become an established investigator in this field, with state-of-the-art-training in the techniques of functional MRI, cognitive neuroscience, and clinical investigation in psychiatry.

Dr. Holt is currently conducting what she hopes will be the definitive functional magnetic resonance imaging study of the neural basis of emotional perception abnormalities in psychosis. The purpose of this research is to identify early markers of illness to allow the development of methods to prevent the onset or slow the progression of schizophrenia. She has evidence that psychotic symptoms are associated with errors in the evaluation of the emotional significance of objects, social interactions and events in the environment. These errors result from a tendency to misattribute emotional significance to neutral or ambiguous information—an “affective misattribution bias.”

To understand the changes in brain function that give rise to this abnormality, Dr. Holt and her team have developed a novel experimental paradigm specifically designed to elicit this bias. Using this paradigm and the spatiotemporal imaging techniques developed at the MGH Martinos Center in Charlestown, her team is attempting to identify the timing and the functional neuroanatomy of this affective misattribution bias in psychotic patients with schizophrenia. After they have characterized the pattern of brain activity associated with this bias in psychosis, they will then determine whether they can detect the identical pattern in at-risk individuals who later go on to develop schizophrenia.

Dr. Robert Carter, Neurosurgery, 2003 Rappaport Research Scholar

Dr. Carter and his team have developed a new strategy for "starving" human brain tumors by decreasing their ability to grow new blood vessels. This was done by creating blocking proteins, which bind to the major molecule, VEGF, that is used by brain tumors to develop new blood vessel growth. With support from the Rappaport Foundation, three different adeno-associated viral vectors encoding these blocking proteins were produced. The team is now in a testing phase of pre-clinical mouse models. The group hopes to complete pre-clinical testing in 2004, and, if successful, apply to the FDA for approval for testing in human brain tumor patients.

Dr. Diana Rosas, Neurology, 2002 Rappaport Research Scholar

Since joining the Neurology faculty, Dr. Rosas has focused her research activities on brain imaging of patients with cognitive disorders, particularly Huntington’s disease. She was promoted to assistant professor at Harvard Medical School and has been successful in getting independent funding from NIH.

As a Rappaport Scholar, she was able to purchase key equipment needed to perform sophisticated data analyses required to develop and validate surrogate biomarkers for Huntington’s disease. She was also able to provide partial salary support for a laboratory research assistant and other related laboratory and office supplies.

Dr. Lee Goldstein, Psychiatry, 2001 Rappaport Research Scholar

Dr. Goldstein has developed a breakthrough optical imaging device that is able to identify a marker of early Alzheimer's disease. Eventually, such a test might be used to measure the effectiveness of new strategies to treat or prevent Alzheimer's symptoms and to diagnose the disease in its earliest stages, when new treatments are likely to be most effective. Dr. Goldstein is associate director for Basic Research at the Center for Ophthalmic Research of the BWH Department of Surgery, a member of the psychiatry departments at MGH and BWH and the MGH Laboratory for Oxidation Biology, and assistant professor of Psychiatry at Harvard Medical School.

Emad Eskandar, Neurosurgery, 2000 Rappaport Research Scholar

Dr. Eskandar is successfully progressing along an academic track with his own lab in the newly developed Center for Nervous System Repair. His research involves the exploration and use of microelectrode recordings to define the function of the basal ganglia and with translational studies to patients with movement disorders and Parkinson's disease.

As a Rappaport Scholar, Dr. Eskandar purchased equipment and software to construct a computer system that collected high-quality intraoperative physiologic data from patients undergoing surgery to treat Parkinson disease. With this system, Dr. Eskandar initiated an IRB approved protocol to study the activity of neurons in the subthalamic nucleus during visually guided movements. The computers and interface cards are used to run the visual experiment and to store and analyze the physiologic data. Dr. Eskandar's group is currently the only one in the world conducting this kind of research. The preliminary results have been extremely interesting and are the subject of upcoming talks at the Congress of Neurologic Surgeons Meeting and American Association of Neurology meeting. In addition, Dr. Eskandar has submitted one paper and is preparing another at the present time.