Benjamin Wolozin, M.D., Ph.D., selected as next chair of CMND for 2013-2015
Benjamin Wolozin, M.D., Ph.D., was selected as the next chair of the National Institutes of Health Cellular and Molecular Biology of Neurodegeneration Study Section.
Dr. Wolozin is a professor in the Department of Pharmacology & Experimental Therapeutics and the Neurology, Principal Investigator of the Laboratory of Neurodegeneration and member of The Boston University Alzheimer’s Disease Center. For more information on Dr. Wolozin’s research, please visit his webpage here.
Congratulations, Dr. Wolozin!
Neurochemical Traffic Signals May Open New Avenues for the Treatment of Schizophrenia
Co-First Author Conor Smith, PhD candidate, Department of Pharmacology & Experimental Therapeutics and Program in Biomedical Neuroscience
Researchers at Boston University School of Medicine (BUSM) have uncovered important clues about a biochemical pathway in the brain that may one day expand treatment options for schizophrenia. The study, published online in the journal Molecular Pharmacology, was led by faculty within the department of pharmacology and experimental therapeutics at BUSM.
Patients with schizophrenia suffer from a life-long condition that can produce delusions, disordered thinking, and breaks with reality. A number of treatments are available for schizophrenia, but many patients do not respond to these therapies or experience side effects that limit their use.
This research focused on key components of the brain known as NMDA receptors. These receptors are located on nerve cells in the brain and serve as biochemical gates that allow calcium ions (electrical charges) to enter the cell when a neurotransmitter, such as glutamate, binds to the receptor. Proper activation of these receptors is critical for sensory perception, memory and learning, including the transfer of short-term memory into long-term storage. Patients with schizophrenia have poorly functioning or “hypoactive” NMDA receptors, suggesting the possibility of treatment with drugs that positively affect these receptors. Currently the only way to enhance NMDA receptor function is through the use of agents called agonists that directly bind to the receptor on the outer surface of the cell, opening the gates to calcium ions outside the cell.
In this study, the researchers discovered a novel “non-canonical” pathway in which NMDA receptors residing inside the cell are stimulated by a neuroactive steroid to migrate to the cell surface (a process known as trafficking), thus increasing the number of receptors available for glutamate activation. The researchers treated neural cells from the cerebral cortex with the novel steroid pregnenolone sulfate (PregS) and found that the number of working NMDA receptors on the cell surface increased by 60 to 100 percent within 10 minutes. The exact mechanism by which this occurs is not completely clear, but it appears that PregS increases calcium ions within the cell, which in turn produces a green light signal for more frequent trafficking of NMDA receptors to the cell surface.
Although still in the early stages, further research in this area may be instrumental in the development of treatments not only for schizophrenia, but also for other conditions associated with malfunctioning NMDA receptors, such as age-related decreases in memory and learning ability.
View the paper online here: http://molpharm.aspetjournals.org/content/early/2013/05/28/mol.113.085696.full.pdf+html
Citation Information: Emmanuel Kostakis*, Conor Smith*, Ming-Kuei Jang, Stella C. Martin, Kyle G. Richards, Shelley J. Russek, Terrell T. Gibbs, David H. Farb. The neuroactive steroid pregnenolone sulfate stimulates trafficking of functional NMDA receptors to the cell surface via a non-canonical G-protein and Ca++ dependent mechanism.
*Co-First Authors
Bioscience Academy student Zainab Mahmud awarded the Paul Queenan Memorial Award for academic excellence
Bioscience Academy student Zainab Mahmud has been awarded the Paul Queenan Memorial Award for academic excellence. Zainab completed her internship in the Laboratory of Molecular Neurobiology under the mentorship of Dr. Marcia Ratner and Dr. David Farb. Upon completion of the Bioscience Academy program requirements, Zainab will receive a Certificate in Applied Biotechnology.
According to the BioScience Academy website, “BioScience Academy is a BU-based federally funded program administered through Metropolitan College and the School of Medicine. The academy offers biotechnology training to unemployed and underemployed Boston area residents who already have an associate’s or bachelor’s degree in science, technology, engineering, or math. The goal is that by their spring 2013 graduation from the two-semester program, these men and women will be headed to new and rewarding laboratory jobs in a healthy and growing Massachusetts job sector. The city of Boston wrote the $1.4 million grant and picked BU as the main training vendor for the program.”
Zainab Mahmud is part of the inaugural class of the Bioscience Academy and is the first recipient of the Paul Queenan Memorial Award for academic excellence. We are so proud of Zainab’s accomplishments and wish her the best in the next phase of her scientific career!
Benjamin Wolozin, M.D., Ph.D., selected to receive the Massachusetts Neuroscience Consortium Award
Congratulations to Benjamin Wolozin, M.D., Ph.D., who was selected to receive the Massachusetts Neuroscience Consortium Award for his proposal to identify the target(s) of action of the TDP-43 inclusion-inhibitory compounds that he has identified.
The Massachusetts Neuroscience Consortium, “is designed to accelerate pre-clinical research available to the pharmaceutical industry, introduce, academic researchers to the challenges of targeted research, and facilitate industry-academic partnerships.”
Dr. Wolozin is a professor in the Department of Pharmacology & Experimental Therapeutics and the Neurology, Principal Investigator of the Laboratory of Neurodegeneration and member of The Boston University Alzheimer’s Disease Center. For more information on Dr. Wolozin’s research, please visit his webpage here.
For more information on the Massachusetts Neuroscience Consortium Award, please visit Boston.com for their press release on the award.
Hat’s off to Dr. Wolozin!
Anurag Singh, Ph.D., receives the American Lung Association Lung Cancer Discovery Award
Congratulations to Anurag Singh, Ph.D., on being awarded the competitive American Lung Association Lung Cancer Discovery Award for his proposal on “Identifying a KRAS-Regulated Micro-RNA Signaling Network in Lung Cancer.”
According to Dr. Singh, “KRAS mutant lung cancers are notoriously refractory to chemotherapeutic agents. This research proposal will seek to identify novel strategies for the clinical management of these cancers with the overall aim of significantly improving the overall survival of cancer patients. The KRAS gene is mutated in 20-30% of non-small cell lung cancers but effective therapeutics that block KRAS function have not been identified thus far. As an alternative approach we will formulate detailed mechanistic information about the mechanisms by which mutant KRAS promotes tumor cell survival and resistance to therapeutic agents. We hypothesize that small non-coding microRNAs play a crucial role in mediating drug resistance. Interfering with the function of these microRNAs will lead to amelioration of drug resistance and will lead to enhanced efficacy of currently available therapeutic agents used to treat to lung cancer.”
Dr. Singh is an assistant professor in the Department of Pharmacology & Experimental Therapeutics and the Department of Medicine, Division of Medical Oncology, Principal Investigator of the Laboratory for Cancer Pharmacogenomics and member of The Cancer Center. For more information on Dr. Singh’s research, please visit his webpage here.
For more information on the Lung Cancer Discovery Award, please visit the American Lung Association website.
Congratulations, Dr. Singh!
Congratulations to Graduating Biomolecular Pharmacology Students!
Featured from left to right: Jiang-Fan Chen, M.D./Ph.D., Catherine Wei, M.D./Ph.D., Carol T. Walsh, Ph.D., and Catherine’s parents
Six students in the Biomolecular Pharmacology Program were honored at graduation ceremonies this past weekend for earning their M.A., Ph.D., or M.D./Ph.D. degrees. Our congratulations go to them for their academic accomplishments, their discoveries through thesis or dissertation research, and their acquisition of professional skills as scientists. Their achievements have been expertly guided by their advisors, whom we congratulate and thank for their dedication to predoctoral training. The students, their degrees, advisors, and thesis or dissertation titles are:
Amy Andreucci, M.A. (January)– Alan Herbert, MB.ChB, Ph.D.
Anti-Inflammatory Drugs: an Appropriate Option for Treating Obesity?
Diane Chan, M.D./Ph.D. – Benjamin Wolozin, M.D./Ph.D.
LRRK2 and HDAC6: Directing Traffic at the Crossroads between Authophagy, Translation, and Neurodegeneration
Jennifer Lynn Duffen, Ph.D. – Kenneth Walsh, Ph.D.
Adiponectin Receptors in Revascularization and Metabolic Dysfunction
Earl Gillespie, Ph.D. – Susan E. Leeman, Ph.D.
Colonic Epithelial Genes in the Transition From Chronic Inflammation to Carcinoma in Colitis-Associated Cancer: Focus on the Truncated Neurokinin-1 Receptor
Catherine Wei, M.D./Ph.D.– Jiang-Fan Chen, M.D./Ph.D.
The Effect of Brain Region-Specific Adenosine A2A Receptor Knockout on Cognition and Psychomotor Behavior in Mice
Stefan Yohe, Ph.D. (January) – Mark Grinstaff, Ph.D.
Superhydrophobic Materials for Drug Delivery
Best wishes to these graduates for the next phase of their careers!
DORA aims to stop the use of the “journal impact factor” in judging an individual scientist’s work
The SAN FRANCISCO DECLARATION ON RESEARCH Assessment (DORA) “aims to stop the use of the ‘journal impact factor’ in judging an individual scientist’s work. The Declaration states that the impact factor must not be used as “a surrogate measure of the quality of individual research articles, to assess an individual scientist’s contributions, or in hiring, promotion, or funding decisions.” DORA also provides a list of specific actions, targeted at improving the way scientific publications are assessed, to be taken by funding agencies, institutions, publishers, researchers, and the organizations that supply metrics. These recommendations have thus far been endorsed by more than 150 leading scientists and 75 scientific organizations, including the American Association for the Advancement of Science (the publisher of Science).
The DORA recommendations are critical for keeping science healthy. As a bottom line, the leaders of the scientific enterprise must accept full responsibility for thoughtfully analyzing the scientific contributions of other researchers. To do so in a meaningful way requires the actual reading of a small selected set of each researcher’s publications, a task that must not be passed by default to journal editors.” – Bruce Alberts
To learn more about the recommendations please click here. The original SAN FRANCISCO DECLARATION ON RESEARCH Assessment (DORA) is accessible here.
BUSM Researchers Discover Possible Mechanism for Anxiety and Depression
“Researchers at Boston University School of Medicine (BUSM) have discovered what they believe to be a major brain mechanism responsible for a heightened state of anxiety and possibly depression. The study, published in the journal Neuropsychopharmacology, involves a protein called pituitary adenylate cyclase-activating peptide (PACAP), a hormone and molecule in the brain, and its relationship with anxiety and depression.
Anxiety disorders are a serious public health problem because they represent the most common mental disturbances in the United States and are responsible for almost one third of the total health care costs. In addition, depression often occurs together with anxiety disorder in patients.
In their study, the researchers were found to be able to induce feelings of anxiousness and depression in a preclinical model after administering PACAP. According to the researchers it was both surprising and very interesting to find that the same molecule could induce both anxious and depressive feelings.
Importantly, the scientists also found that the mechanism of the anxiety and depression-inducing effects of PACAP involves another important and well known molecule and hormone, called corticotropin-releasing factor (CRF). Indeed, when the authors provided PACAP to the model, they observed an increase in the production of CRF in two important regions of the brain, the hypothalamus and the amygdala. More importantly, when the authors introduced a substance that blocked the receptors of CRF, PACAP could no longer induce anxiety and depression.
“In humans, a dysfunction of the amygdala PACAP system may therefore be responsible for the development of conditions involving atypical responses to stressors, including generalized anxiety, PTSD and depression,” said senior study author Valentina Sabino, PhD, assistant professor of pharmacology and psychiatry in the Department of Pharmacology at BUSM as well as co-director of the Laboratory of Addictive Disorders
Also contributing to this study were Riccardo Dore, PhD; Attilio Lemolo, PhD, Karen L. Smith, PhD, Xiaofan Wang PhD and Pietro Cottone, PhD. The Laboratory of Addictive Disorders at Boston University School of Medicine is continuing this line of research to better understand the neurobiology of the PACAP system, with the hope of ultimately developing new therapeutic agents for the treatment of these debilitating psychiatric diseases.
Funding for this study was provided by the National Institute of Mental Health, the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. In addition, funding was made available by the Peter Paul Career Development Professorship and by Boston University’s Undergraduate Research Opportunities Program.”
Originally published by Boston University School of Medicine
BUSM Researchers Discover Possible Mechanism for Anxiety and Depression
“Researchers at Boston University School of Medicine (BUSM) have discovered what they believe to be a major brain mechanism responsible for a heightened state of anxiety and possibly depression. The study, published in the journal Neuropsychopharmacology, involves a protein called pituitary adenylate cyclase-activating peptide (PACAP), a hormone and molecule in the brain, and its relationship with anxiety and depression.
Anxiety disorders are a serious public health problem because they represent the most common mental disturbances in the United States and are responsible for almost one third of the total health care costs. In addition, depression often occurs together with anxiety disorder in patients.
In their study, the researchers were found to be able to induce feelings of anxiousness and depression in a preclinical model after administering PACAP. According to the researchers it was both surprising and very interesting to find that the same molecule could induce both anxious and depressive feelings.
Importantly, the scientists also found that the mechanism of the anxiety and depression-inducing effects of PACAP involves another important and well known molecule and hormone, called corticotropin-releasing factor (CRF). Indeed, when the authors provided PACAP to the model, they observed an increase in the production of CRF in two important regions of the brain, the hypothalamus and the amygdala. More importantly, when the authors introduced a substance that blocked the receptors of CRF, PACAP could no longer induce anxiety and depression.
“In humans, a dysfunction of the amygdala PACAP system may therefore be responsible for the development of conditions involving atypical responses to stressors, including generalized anxiety, PTSD and depression,” said senior study author Valentina Sabino, PhD, assistant professor of pharmacology and psychiatry in the Department of Pharmacology at BUSM as well as co-director of the Laboratory of Addictive Disorders
Also contributing to this study were Riccardo Dore, PhD; Attilio Lemolo, PhD, Karen L. Smith, PhD, Xiaofan Wang PhD and Pietro Cottone, PhD. The Laboratory of Addictive Disorders at Boston University School of Medicine is continuing this line of research to better understand the neurobiology of the PACAP system, with the hope of ultimately developing new therapeutic agents for the treatment of these debilitating psychiatric diseases.
Funding for this study was provided by the National Institute of Mental Health, the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism. In addition, funding was made available by the Peter Paul Career Development Professorship and by Boston University’s Undergraduate Research Opportunities Program.”
Originally published by Boston University School of Medicine
Robert Freilich wins First Prize at 19th Annual Henry I. Russek Student Achievement Day
Three students in the Biomolecular Pharmacology Program were honored at the 19th Annual Henry I. Russek Day Student Achievement Day Friday, 10 May. These students have distinguished themselves not only as gifted researchers in their mentor’s laboratory but also as dedicated members of their department, program, and surrounding community.
The following Biomolecular Pharmacology students received awards:
First Prize – Robert Freilich
Second Prize – Tara Vanderweyde
Honorable Mention – Tracey Tucker
For more information about the 19th Annual Henry I. Russek Student Achievement Day, please click here.
