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.
With sadness I share that Terrell Gibbs, PhD, associate professor of Pharmacology & Experimental Therapeutics, died Friday, August 15, at M.D. Anderson Cancer Center in his home state of Texas. A member of the BUSM faculty for 24 years, Dr. Gibbs received his undergraduate degree in biology from MIT and his doctoral training in pharmacology from Harvard Medical School. He pursued his interests in neuropharmacology, first at Downstate Medical Center in the Department of Anatomy & Cell Biology at SUNY Health Science Center in Brooklyn, NY, and then at Boston University working in close collaboration with Pharmacology Chair Dr. David Farb.
Dr. Gibbs’ research involved elucidation of the molecular mechanisms of modulation of GABAergic function by benzodiazepines and neurosteroids and of CNS abnormalities such as autism. His discoveries were revealed in more than 45 publications and many abstracts presented at the Society of Neuroscience Annual Meetings.
A recent recipient of the Excellence in Education and Mentoring Award from the Neurosteroid Congress, he played a key role in the design and implementation of the curriculum for the Biomolecular Pharmacology Predoctoral Training Program at Boston University and guided innumerable PhD candidates. He taught medical, dental, and master’s degree students at BU 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.
His interest in pharmacologic research in many areas and rational evaluation of evidence of drug efficacy and safety were hallmarks of his approach as an educator and served as an outstanding role model for both students and faculty.
Dr. Gibbs also was renowned for his expertise in the martial arts, which he occasionally practiced on the Talbot Green.
He will be greatly missed by his students and his faculty and staff colleagues.
He is survived by his step-mother, brother and sister, half-sister and half-brother, and nieces and nephews.
To make a donation in memory of Dr. Gibbs please click here.
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.
Dr. Sophie Desbiens, formerly Principal Associate at Decision Resources, has accepted a position as Assistant Director for Adaptive Licensing at MIT’s Center for Biomedical Innovation in the New Drug Development Paradigms (NEWDIGS) program.
According to the NEWDIGS website, the program “is a unique collaborative ‘think and do’ tank focused on enhancing the capacity of the global biomedical innovation system to more reliable and sustainably deliver new, better, affordable therapeutics to the right patients faster.
By bringing together diverse collaborators within a safe haven setting, and leveraging MIT expertise in systems engineering, this group is well positioned to inform and enable meaningful high-impact change involving the coordinated evolution of technologies, processes, policies, and people required to achieve its mission.”
Dr. Sophie Desbiens completed her dissertation work under the mentorship of Dr. David H. Farb, Professor and Chair of Pharmacology, in the Laboratory of Molecular Neurobiology and graduated in 2009. The title of her dissertation was “Therapeutic Agents for Cocaine Addiction: A Systems Pharmacology Approach.”
Congrats on the new position, Sophie!
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.
Iriny Ekladious, a second year PhD student in the joint Biomedical Engineering and Biomolecular Pharmacology Program, was recently awarded the National Science Foundation Graduate Research Fellowship.
The program “recognizes and supports outstanding graduate students” pursuing graduate degrees in various NSF-supported programs across the country and “has a long history of selecting recipients who achieve high levels of success in their future academic and professional careers.”
This year alone, the National Science Foundation received over 14,000 competitive applications and only made 2,000 fellowship award offers. The chosen fellows “are anticipated to become knowledge experts who can contribute significantly to research, teaching, and innovations in science and engineering.”
Iriny was also recently recognized for her service to the Boston University community as a Resident Assistant for Boston University’s Women in Science & Engineering (WISE) specialty housing. In an effort to create more support for women planning to major in STEM programs, BU opened a specialty community residence.
“It’s important to have a community of other women when you’re studying in the STEM fields,” says resident assistant Iriny Ekladious (ENG’17), a second year graduate student. “It can be intimidating, and women often feel outnumbered. Having a community like this gives students confidence and empowers them to say, ‘I’m good at this and I can do this,’ despite all the hurdles.”
Iriny’s dissertation work involves synthesizing, characterizing, and assessing the efficacy of pH-sensitive expansile nanoparticles for the local delivery of chemotherapeutic agents under the mentorship of Dr. Mark Grinstaff in the Center for Nanoscience and Nanobiotechnology.
We are thrilled that Iriny has been recognized for extraordinary contributions in the engineering and field and for her exemplary leadership serving undergraduates in the WISE house!
Selected excerpts taken from an article originally published by BU Today on April 16, 2014.
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.
Hui Feng spends a lot of time staring through zebra fish. Through because these vertebrates, which have a great deal of genetics in common with humans, are transparent. In fact, one particular breed, called Casper—after the Friendly Ghost—is so phantasmal that Feng says that “you can read newspapers through this fish.”
Feng doesn’t read the news through them, though. The School of Medicine assistant professor of pharmacology and medicine is more interested in tracking the pathways of dyed tumor cells as they metastasize through the zebra fish’s vasculature, which is tinted a contrasting color. In the less than two years since her tank-filled lab opened, she has identified genes that, when blocked with targeted treatments, could prevent the metastasis of certain types of cancer, like the most stubborn forms of leukemia.
In recognition of her groundbreaking work, Feng was awarded the Ralph Edwards Career Development Professorship, which recognizes MED researchers. The award was made possible this year by the estate of obstetrician and gynecologist Ralph Edwards (MED’52).
Feng, director of the Laboratory of Zebrafish Genetics & Cancer Therapeutics, says the honor reminds her that University officials appreciate faculty research and they want to support it. “It’s not just about the money,” she says. “The spiritual or mental support really means so much to us.”
Karen Antman, MED dean and Medical Campus provost, recalls the researcher’s discoveries early in her career, which found their way to top-tier research journals, including Nature, Cell Biology, Cancer Cell, the Journal of Experimental Medicine, and PNAS. A graduate of Beijing Medical University, Feng completed a master’s in cardiovascular pharmacology at Peking Union Medical College and a doctorate in cellular biology at the University of Georgia.
“Since joining the School of Medicine faculty,” Antman says, “Dr. Feng has demonstrated an exceptional level of scholarship, mentorship, teaching, and collegiality and quickly established herself as an independent research scientist, effectively and efficiently setting up a robust research program.”
Feng is one of three assistant professors who were given career development awards, which recognize junior faculty who have been at the University for less than two years and have held no prior professorships. Cornel Ban, a College of Arts & Sciences assistant professor of international relations, received the inaugural Stuart and Elizabeth Pratt Career Development Professorship, dedicated to CAS scholars. And Nachiketa Sahoo, a School of Management assistant professor of information systems, was awarded the Reidy Family Career Development Professorship, which has recognized faculty members in SMG and the College of Engineering in alternating years since 2010.
Contributions from BU trustee Stuart W. Pratt (CAS’69) and his wife, Elizabeth, and trustee Richard D. Reidy (SMG’82) and his wife, Minda G. Reidy (SMG’82, GSM’84) made the professorships possible.
Each award comes with a three-year nonrenewable stipend used to support scholarly or creative work and to cover a portion of the faculty member’s salary. Deans of the respective schools or colleges nominate faculty for these honors, and the Office of the Provost makes the final selections.
“We are extremely grateful to Stuart and Elizabeth Pratt, Richard and Minda Reidy, and posthumously, Ralph Edwards for their generosity and for the vision they’ve shown in supporting the future of these very important fields,” says Jean Morrison, University provost and chief academic officer. These three professors were recognized for “their extraordinary accomplishments in areas of study, passion for the creation and transmission of knowledge, and their efforts to enhance the student experience.”
Ban’s research has focused on economic issues in Brazil, Spain, and Romania, and spans three principal topics: international finance, international economic organizations, and the diffusion of international economic ideas. He describes his first book, Governing Crises: The International Politics of Crisis Economics from Bretton Woods to the Great Recession, not yet published, as “a cautionary tale about how much we don’t know about how the financial markets work.” He is an expert on the failure of economic models used by governments or international banks to predict the financial crisis that swept the world within the past decade.
Ban earned a bachelor’s from Babes-Bolyai University, in Romania, a master’s degree from the University of Delaware, and a doctorate in political science from the University of Maryland. He says the award will give him the time and funding to launch his next book project, which will focus on the dynamics of international finance over the past couple of decades. “Without this kind of support,” he says, “I could not get it done.”
Andrew Bacevich, a CAS professor of history and international relations and acting chair of international relations, calls Ban an “emerging superstar” in the department. “Since his arrival a year ago, he has become a valued asset,” he says. “His performance as a teacher and scholar has demonstrated that he is precisely the sort of young faculty member for whom the Stuart and Elizabeth Pratt Career Development Professorship is designed.”
Sahoo holds a master’s degree in knowledge discovery and data mining and a doctorate in information systems and management, both from Carnegie Mellon University. His current research focus is on improving personalized information filtering techniques, such as that used by Netflix and Amazon, to help customers find products that best match their past interests. Recognizing that people are dynamic and that their preferences change over time, he has adjusted these filtering techniques so that they show more accurate recommendations across a variety of platforms.
In a separate branch of research, Sahoo is analyzing the messages exchanged between individuals on corporate social media, such as blogs, to identify expertise that exists inside a company.
“New technologies to help people connect to each other are exacerbating the problem of information overload at a personal level,” says Sahoo. “There is too much information to sift through and there is limited time. It’s important to develop tools and techniques that help us find the bits of relevant information faster.”
Sahoo says he will use the award to hire a research assistant to help with data collection and analysis.
“Dr. Sahoo is a wonderful addition to our faculty: a productive researcher, a great colleague, and a committed teacher,” says Kenneth Freeman, SMG’s Allen Questrom Professor and Dean.
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!