Category: Recent News
The Laboratory of Cancer Cell Biology has identified the tumor suppressor mechanism that prevents the oncogenic growth of cells harboring an abnormal number of chromosomes. The study, published in the journal Cell, was led by Neil J. Ganem, PhD.
Tetraploid cells, which are a common byproduct of cell division failure, are genomically unstable and have the capacity to facilitate tumorigenesis. Recent estimates suggest that ~40% of all solid tumors have undergone a transient tetraploid intermediate at some point during their evolution, suggesting that tetraploidy plays significant roles in both the development and/or progression of human malignancies. Given the potentially oncogenic consequences of tetraploidy, it is not surprising that tumor suppression mechanisms have evolved that prevent the proliferation of these cells. However, unlike other common cellular insults that trigger cell cycle arrest, such as DNA damage, the mechanisms governing cell cycle arrest in response to tetraploidy have been poorly defined.
To understand the mechanism of growth arrest in tetraploid cells, Dr. Ganem and colleagues combined genome-wide RNAi screening and in vitro evolution approaches to comprehensively identify all of the genes required to stall the growth of tetraploid cells. Collectively, these data revealed that the Hippo tumor suppressor pathway is specifically activated in tetraploid cells, both in vitro and in vivo, and that this is the pathway that prevents tetraploid proliferation. The authors pinpointed that defects in the cytoskeleton of tetraploid cells represented the initial trigger for Hippo pathway activation. Notably, analysis of a broad spectrum of human cancers revealed that near-tetraploid tumors frequently adapt to overcome Hippo signaling, suggesting that inactivation or bypass of this pathway may be a prerequisite for the development of high-ploidy tumors. “This work may help guide the development of new therapies that specifically target tumor cells with abnormal numbers of chromosomes, while sparing the normal healthy cells from which they originated,” explained corresponding author Dr. Ganem, PhD, Assistant Professor of Pharmacology & Experimental Therapeutics and Medicine in the Shamim and Ashraf Dahod Breast Cancer Research Laboratories at BUSM.
The study was highlighted with a preview article in Cell and by the journals Science Signaling, Cancer Discovery, and Nature Reviews Cancer. The article can be read online at: http://www.cell.com/cell/abstract/S0092-8674(14)00820-4.
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 cognitive deficits seen in schizophrenia. The study, published online in the journal Molecular Pharmacology, was led by faculty members David H. Farb, PhD, Terrell T. Gibbs, PhD, and Shelley J. Russek, PhD in thedepartment of pharmacology & experimental therapeutics at BUSM.
Patients with schizophrenia suffer from a life-long condition that can produce cognitive deficits, delusions, disordered thinking, and breaks with reality. A number of treatments are available for the treatment of schizophrenia, but many patients do not respond to these therapies or experience side effects that limit their use. There is no current treatment for the cognitive deficits experienced in schizophrenia.
The healthy brain is made up of billions of cells including the primary signaling cells called neurons, that are responsible for managing everything the body does: including movement, eating behavior, and memory formation. These neurons acts like a miniature computer and are controlled by substances called neurotransmitters that, like bits in a computer chip, may be “turned on” or “turned off” depending on the specific signals being integrated. Neurotransmitters latch onto a cell via a specific receptor, like a key fits into a lock.
In schizophrenia, it is thought that certain neurons don’t “turn on” as well when exposed to a certain neurotransmitter, the amino acid glutamate, may not be sensed by one of its key receptors (the NMDA receptor) whose diminished function may be the possible culprit for these sluggish cells. It is thought that this deficit can at least partially be responsible for symptoms seen in schizophrenics.
Currently the therapeutic means for making these cells more “sensitive” to glutamate can be toxic to the brain.
In this study, researchers discovered that another, naturally occurring steroid within the brain, known as PregS, may be able to bypass this toxic effect, and “turn on” neuron communication safely through a novel mechanism. The implication is that a deficit in the amount of this novel steroid may underlie deficits in signaling and that stimulation using therapeutics that elevate its levels in the brain may decrease or eradicate some of the debilitating symptoms seen in schizophrenia.
Although still in the early stages, further research in this area may be instrumental in the identification and development of treatments not only for schizophrenia, but also for other neurological conditions, such as age-related decreases in memory and learning ability.
Earl Gillespie, Ph.D., a Postdoctoral Researcher at Boston University School of Medicine and an alumni of the Biomolecular Pharmacology Program, will join Avalere Health in Washington, DC as an FDA Policy Fellow this summer.
According to the Avalere Health website, the highly selective FDA Policy Fellowship Program allows participants to, “spend 6 months immersed in health and life science regulatory policy and strategy issues to help support the efforts of Avalere clients that include some aspect of FDA related issues. Fellows will collaborate within [the] existing FDA team to increase Avalere’s presence and visibility as experts and thought leaders in the FDA space.”
Dr. Earl Gillespie completed his dissertation work under the mentorship of Dr. Susan E. Leeman, Professor of Pharmacology, and Dr. Arthur F. Stucchi, Research Associate Professor of Surgery, and graduated in January 2013. The title of his dissertation was “Colonic Epithelial Genes in the Transition From Chronic Inflammation to Carcinoma in Colitis-Associated Cancer: Focus on the Truncated Neurokinin-1 Receptor.”
We are so very proud of Earl and wish him the best in this new phase of his career!
Researchers in the Laboratory of Addictive Disorders have discovered that impulsivity is a risk factor for food addiction . Results of the study, published online in Neuropsychopharmacology , suggest that impulsivity promotes pathological overeating.
Dr. Terry Gibbs receives the Excellence in Education and Mentoring Award from the Neurosteroid Congress
Terrell Gibbs, Ph.D., Associate Professor of Pharmacology & Experimental Therapeutics, received the Excellence in Education and Mentoring Award at the Neurosteroid Congress held on April 3, 2014 in Durham, North Carolina.
Terry has served the scientific community with distinction for over 30 years. With undergraduate and doctoral training at MIT and Harvard Medical School, respectively, Terry pursued his interests in neuropharmacology, first at Downstate Medical Center and then at Boston University. His research has involved elucidation of the molecular mechanisms of CNS abnormalities such as autism and of CNS classes of agents such as benzodiazepines and neurosteroids. A long-standing collaboration with David Farb, Ph.D., Chair of Pharmacology at BU, has been an especially productive one in their joint efforts in the pursuit of molecular mechanisms of CNS phenomena. His work as a faculty member has also been characterized by a strong commitment to the education of students in various professional degree programs. Terry has played a key role in the design and implementation of the curriculum for the Biomolecular Pharmacology Predoctoral Training Program at Boston University, supported by NIGMS since 1997. He has guided innumerable PhD candidates through the concepts underlying ligand-receptor interactions, preparation for and successful completion of qualifying examinations, and the rigors of dissertation writing and defense. Medical, dental, and MA students at Boston University have also benefited from his remarkable skill at explaining the principles of pharmacology and the actions of drugs affecting the peripheral and central nervous system. All medical students over the past 23 years have learned the principles of pharmacodynamics under his tutelage and that his dedication to teaching the foundation of pharmacological principles has been a key component of their success on the boards.
Terry’s interest in pharmacologic research in many areas, and the rationale evaluation of evidence of drug efficacy and safety, have been hallmarks of his approach as an educator and served as an outstanding role model for both students and colleagues. His contributions to research have been numerous in the fields of benzodiazepines as modulators of GABAergic function and neuroactive steroids.
At the Student Award Ceremony on Match Day, March 21, 2014, Rebecca Burke was awarded the Joseph Cochin Award in Pharmacology and Medical Ethics. This award honors the memory of Joseph Cochin, MD, PhD, who served as Professor of Pharmacology and Experimental Therapeutics at BUSM for many years. Dr. Cochin was an internationally recognized expert on opioid analgesia, pain control and medical ethics. Becky, a student in the Biomolecular Pharmacology Training Program from 2008-2012, received this award in recognition of her high achievement in pharmacology and accomplishments in research under the mentorship of Jan K. Blusztajn, PhD. Becky will receive her MD and PhD degrees at the BUSM May Graduation Ceremony and will continue her professional training with a residency at the University of Virginia in Neurological Surgery. Congratulations to Becky!
Richard D. Wainford, Ph.D., F.A.H.A., Assistant Professor of Pharmacology and Medicine, Division of Cardiovascular Medicine and member of The Whitaker Cardiovascular Institute at Boston University School of Medicine, has been awarded the 2014 Arthur C. Guyton Award for Excellence in Integrative Physiology and Medicine by The American Physiology Society (APS). This award is given annually to an individual who demonstrates outstanding promise based on his/her research program in feedback controls systems, quantitative modeling, and integrative physiology. The recipient is selected by members of the APS Awards Committee. In addition to the prestige of the award, the recipient is given $15,000 to support their research. Formal presentation of the Arthur C. Guyton Award will take place at the APS Business Meeting at the 2014 Experimental Biology Annual Meeting in San Diego, CA on April 29, 2014.
As Director of the Laboratory of Cardiovascular Renal Research, Dr. Wainford’s research focuses on the central neural control of fluid and electrolyte homeostatis and blood pressure regulation. Please visit Dr. Wainford’s Laboratory website to learn more about his research.
Dr. Camron Bryant’s symposium proposal for the 2014 Annual Genes, Brain and Behavior Meeting of the International Behavioural and Neural Genetics Society Meeting has been accepted as one of six symposia scheduled for this year’s meeting. The 16th annual conference will be held in Chicago, IL from May 10-13.
The title of the symposium that Dr. Bryant will chair is, “Behavioral, neural and genetic studies of compulsive eating in model organisms and humans.” The objective of this symposium is to highlight recent behavioral, neural, and genetic studies of compulsive eating that lie within the framework of addiction and to inform future studies in model organisms and humans.
Congratulations, Dr. Bryant!
Shelley J. Russek, PhD, professor of pharmacology at Boston University School of Medicine (BUSM), and director of the School’s Graduate Program for Neuroscience, was recently honored with an award from the CURE (Citizens United for Research in Epilepsy) Foundation. The prestigious award, given as well to her colleague Amy Brooks-Kayal, MD, from University of Colorado Denver, will fund research studies for new drugs for epilepsy treatment.
Approximately 65 million people worldwide have epilepsy. Although certain brain injuries are known to predispose someone to epilepsy, there are no treatments that reduce this risk. Russek and her colleagues have found that an important cellular signaling pathway, the JAK/STAT pathway, is activated after brain injuries that lead to epilepsy, and that inhibiting this activation reduces subsequent seizure frequency in an experimental model. “We expect to identify lead JAK/STAT inhibitors that can be advanced towards clinical testing to prevent or inhibit development of acquired epilepsy following brain injury,” explained Russek.
CURE was founded by parents of children with epilepsy who were frustrated with their inability to protect their children from the devastation of seizures and the side effects of medications. Unwilling to sit back and accept the debilitating effects of epilepsy, these parents joined forces to spearhead the search for a cure. Each year, grants are funded based on promising trends in the field and the potential for breakthroughs in a specified area. Russek was selected with the assistance of the CURE Scientific Advisory Board, the Lay Review Council, and the scientific peer reviewers who generously volunteer their time to CURE.
CURE has raised more than $26 million to fund research and other initiatives. CURE funds seed grants to young and established investigators to explore new areas and collect the data necessary to apply for further funding by the National Institutes of Health. To date, CURE has awarded 151 cutting-edge projects.
Originally posted on the Boston University Medical Campus website.
The Peter F. McManus Charitable Trust Foundation recently honored Dr. Valentina Sabino for the second time with a grant to research the causes of alcohol addiction. The title of her approved project is “Neurobiological Bases of Alcohol Addiction.”
According to Dr. Sabino, “alcoholism constitutes one of the most serious public health problems worldwide. The World Health Organization estimates that about 2 billion people worldwide consume alcoholic beverages, of which 76.3 million have alcohol use disorders. Alcohol is estimated to cause 20%–30% of esophageal cancer, liver cancer and cirrhosis, homicide, seizures, and motor vehicle accidents, causing 3.2% of the total deaths.
This project will systematically explore the role of an understudied receptor system, the Sigma receptors, in genetic and chronic ethanol-induced animal models of alcoholism. The focus will be the Nucleus Accumbens, an important brain region for alcohol and drug addiction, proposed as being the specific region where Sigma receptors mediated neuroplasticity in addicted brains.
These experiments will provide insights into this novel receptor system as a key mechanism involved in excessive drinking and alcohol-seeking behavior and propose a novel therapeutic target for alcohol addiction.”
Dr. Sabino received her Ph.D. in Pharmacology in 2006. She is an Assistant Professor in the Department of Pharmacology & Experimental Therapeutics and Department of Psychiatry, and Co-Director of the Laboratory of Addictive Disorders at Boston University School of Medicine.
Congratulations, Dr. Sabino!