George Tuszynski

Like many biomedical researchers, George Tuszynski would like to cure cancer. But in his quest, he may have stumbled across a solution to a humbler problem: wrinkled skin. Professor of Neuroscience in Temple’s School of Medicine and Professor of Biology in Temple’s College of Science and Technology.

Tuszynski and his group, along with In Kine Pharmaceutical Co., a small pharmaceutical company based in Blue Bell, PA, have developed three molecules that prevent tumor growth by inhibiting blood vessel formation, which is called angiogenesis. One of the molecules has been named angiocidin, while the other two are peptides.

Angiocidin, a tumor-inhibiting novel protein discovered by Temple University researchers, was revealed last year to have a therapeutic application in treating leukemia. The study, “The Novel Angiogenic Inhibitor, Angiocidin, Induces Differentiation of Monocytes to Macropahges,” published in 2008 in the journal Cancer Research. The research was done by Temple biology doctoral student Anita Gaurnier-Hausser under Tuszynski's direction.

What cancer has in common with aging skin is that in both conditions, cells have stopped growing properly. Stem cells, characterized by their ability to renew themselves through mitotic cell division and differentiating into a diverse range of specialized cell types, create healthy well-behaved cells. Tuszynski has shown that he "can repair damaged skin. Given the right stem cells, you can make the cells grow up and behave."

“Angiocidin is a protein that has a lot of anti-cancer activity and inhibits angiogenesis, a physiological process involving the growth of new blood vessels from pre-existing vessels, which is a fundamental step in the transition of tumors from a dormant state to a malignant state,” said Tuszynski, who discovered the protein.

Tuszynski said that over the years, the researchers had looked at the protein’s effect on solid tumors like breast cancer, prostate cancer and colon cancer. 

“All of these cancers are inhibited by Angiocidin by virtue of the fact that this protein inhibits vascularization or the formation of new vessels,” he said. “We decided we wanted to look to see if Angiocidin had any effect on hematologic malignancy, and we chose leukemia.”

Tuszynski said leukemia cells arise from monocytes, a specific white blood cell that is a part of the human body’s immune system that protects against bloodborne pathogens and moves quickly to sites of infection. As monocytes enter tissue, they undergo a series of changes to become macrophages.

When the researchers treated the leukemia cells, “our molecule was able to induce a differentiation of these monocytic leukemia cells into a normal, macrophage-like phenotype,” he said.

“This indicates perhaps a new therapeutic application for this protein, that it could differentiate hematologic malignancies into a normal-like state, allowing then for chemotherapy because normal cells are susceptible to chemotherapy treatment,” said Tuszynski, who is also a member of the Sol Sherry Thrombosis Research Center in Temple’s School of Medicine.

He added, however, that Angiocidin must remain present with the differentiated cells or they will revert back to their leukemia phenotype. “We haven’t repaired the genetic abnormality in the cell, but what we have done is push them into a more normal phenotype that could then be treated more easily.”

Tuszynski also said that the research demonstrates the ability of Angiocidin to stimulate the body’s immune system by differentiating monocytic cells into macrophages, which function to ingest bacteria and protein debris as part of the immune system.

“We did gene array analysis of the differentiated versus the undifferentiated cells and we discovered that there were many genes characteristic of immune cells that were up-regulated in the differentiated leukemia cells,” he said. “That Angiocidin can stimulate differentiation and stimulate the immune system is basically a new activity that we discovered with this protein that we had never really anticipated before.”

The research was funded by the National Institutes of Health and Temple University.

In 1987, our laboratory first showed that thrombospondin -1 (TSP-1), a platelet protein, functioned as a cell and platelet adhesive protein and that TSP-1 could promote metastasis formation in a murine model of experimental metastasis. Since then we have identified structural domains within the TSP-1 molecule and a new TSP-1 receptor that may mediate cell-cell and cell-substratum interactions operative during the metastatic cascade and the process of angiogenesis. We found that a number of peptides homologous to CSVTCG promoted the adhesion of a variety of normal and tumor cells and inhibited platelet aggregation and tumor cell metastasis, whereas control peptides had no effect. Our results further demonstrated that these peptides inhibited tumor lung metastases and angiogenesis presumably by competing with endogenous TSP-1 for TSP-1 tumor cell receptor sites. This conclusion was further supported by the observation that anti-CSTSCG antibody, which specifically recognized TSP-1, inhibited TSP-1-dependent cell adhesion, platelet aggregation, and tumor cell metastasis, whereas control IgG had no effect. These results suggest that CSVTCG and CSTSCG present in the type I repeat sequences of TSP-1 function in the adhesive interactions of TSP-1 that mediate platelet aggregation, angiogenesis and tumor cell metastasis. 

The TSP-1 receptor specific for the CSVTCG residues in the type 1 repeats of TSP-1 was isolated from lung carcinoma by CSVTCG-Sepharose chromatography. Anti-receptor IgG and inhibited lung carcinoma cell spreading and adhesion and platelet adhesion on TSP-1 but not on fibronectin and laminin. Anti-CSVTCG receptor antibody blocked breast cancer invasion in vitro and metastasis and tumor progression in an in vivo athymic model of breast cancer progression. These data as well as immunohistochemical studies showing that this receptor highly over-exepressed in breast carcinoma and its neovasculature as well as many other tumors, including lung, melanoma, ovarian, prostate, pancreatic, colon, gastric, and hepatocelluar carcinoma and that this receptor is predictive of poor patient outcome in squamous carcinoma of the head and neck strongly support the conclusion that both TSP-1 and its receptor mediate cancer progression. 

The receptor has recently been cloned and expressed as a soluble protein in bacteria. Recombinant protein, referred to as angiocidin, specifically inhibited endothelial adhesion, tube formation and viability, while having no effect on a variety of cells including fibroblasts, smooth muscle cells, and tumor cells. Angiocidin localized to the vasculature and inhibited Lewis Lung carcinoma and B16F10 melanoma growth in mice by more than 95%. Similarly, a monoclonal receptor antibody inhibited more than 50% tumor growth. Therefore, angiocidin may be new target for the development of an anti-angiogenic agent for the treatment of cancer. 

Based on these results, we believe that CSVTCG peptides and the CSVTCG specific TSP-1 receptor (angiocidin) are targets for the development of cancer therapeutics, angiogenesis inhibitors and imaging agents as well as anti-thrombotics. Preclinical studies are now underway in preparation for the use of angiocidin, anti-angiocidin antibodies and the CSVTCG peptides for the treatment of cancer in man. Finally our laboratory is searching for new molecules and new mechanisms that can be targeted for development of cancer therapeutics and diagnostics. In collaboration with Dr. Mahesh Sharma, we have identified annexin II as a potential receptor mediating angiogenesis and tumor progression. We have developed a monoclonal annexin II antibody that reduces tumor growth by more than 50%. This antibody may also find utility as a diagnostic tool for the detection of annexin II in sera and solid tumors.

Tom Gould

Thomas J. Gould

 

Learning and addiction are inked in the brain in unexpected ways, according to Thomas J. Gould, a professor of pharmacology at Temple University. The well-documented learning-related changes in the strength of neuronal connections in the brain not only underlie memory formation and storage but are also affected by drugs of abuse, such as nicotine or alcohol. The goal of Gould's research is to use genetic, pharmacological, behavioral, molecular and electrophysiological techniques to study the effects of these drugs on the neurobiology of learning and memory.  

In 1988, the US Surgeon General concluded that tobacco products are addictive and that nicotine is the main pharmacological agent in tobacco responsible for tobacco's addictive nature.  Many questions remain, however, about nicotine.  It is not completely understood what nicotine's effects on neurological/behavioral function are nor is it understood why nicotine is addictive.  One reason for the incomplete understanding of nicotine addiction may be that addiction is a complex disorder with many factors contributing to the disease.  The symptoms of nicotine withdrawal, which can include physical symptoms, impairments in cognition, and mood dysfunction may be a critical factor in the high relapse rates that occur in cigarette smokers.  Furthermore, genetic factors may modulate the acute, chronic, and withdrawal effects of nicotine on cognition.  Although animal models have provided useful insight into the somatic and affective symptoms of nicotine withdrawal, little animal research has focused on the effects of nicotine withdrawal on learning. 

 Research from Gould's lab uses contextual fear conditioning, a hippocampus-dependent form of classical conditioning, as an animal model for the effects of nicotine on cognition. The goals of the research are: to investigate the effects of nicotine on learning, to identify the cellular and molecular mechanisms that are altered by nicotine use, and to identify genetic factors that may contribute to nicotine-associated neurobehavioral effects.  Our laboratory uses behavioral, pharmacological, genetic, molecular, and electrophysiological approaches to address these questions. 

Nicotine addiction is a disorder that may be maintained by many factors, including nicotine withdrawal-associated deficits in cognitive processes.  One goal of our laboratory is to test pharmacological agents that can potentially reduce nicotine withdrawal-associated deficits in cognition.  Previous research has established that the noradrenergic system is involved in both learning and attention, and recent studies from our lab have demonstrated that nicotine withdrawal-associated deficits in contextual fear conditioning can be reversed by both nicotine replacement and by norepinephrine reuptake inhibitors.  By identifying cellular and molecular processes that can ameliorate the effects of nicotine, more effective smoking cessation strategies can be developed.

The Effects of Alcohol and Nicotine On Cognition 

Alcohol is frequently referred to as a "gateway" substance to nicotine use and abuse, and research has demonstrated that nicotine use in adolescents can predict a transition from social to problem drinking.  However, the reasons for why these two drugs are co-abused remain unclear, although several factors are likely to be involved.  One possible explanation for the co-abuse of nicotine and alcohol is that nicotine may reduce some of the negative symptoms of alcohol, such as disrupted cognition.  Evidence in favor of this explanation comes from studies that have shown that alcohol impairs learning in hippocampus-dependent and independent procedures, while nicotine can reverse these deficits.  An additional goal of our laboratory is to examine the neural substrates underlying the interactive effects of alcohol and nicotine on learning, and also to understand the effects of alcohol on learning when administered alone.  Understanding the interactive effects of these drugs on cognition will aid in developing more effective treatments for both alcoholism and nicotine addiction.

Scott Rawls

 Scott Rawls is an assistant professor of pharmacology in the Department of Pharmaceutical Sciences at Temple University School of Pharmacy and Research Professor at the Center for Substance Abuse Research in Philadelphia, Pennsylvania. Dr. Rawls holds a bachelor’s of science degree in Chemistry and an earned a doctorate in neuroscience in 1999.

Rawls maintains an active research laboratory funded by the National Institutes of Health (NIH) and the Pennsylvania Department of Health. He has published over 30 articles in peer-reviewed journals over the past five years. In addition, Pharm.D. students conducting research under the direction of Dr. Rawls have received several research fellowships, including the Pfizer Undergraduate Summer Research Award and American Foundation of Pharmaceutical Education Award.

Rawls is also active in the education of both Pharm.D. (pharmacy) and graduate students. In the Pharm.D. curriculum, Dr. Rawls coordinates the Anatomy and Physiology course and teaches the cardiovascular and renal sections in the Pharmacology course. He is the recipient of several teaching awards, including the American Association of Colleges of Pharmacy Teaching Award in 2006 and Biological Sciences Teaching Award (Washington College) in 2003. Dr. Rawls is also co-author of a pharmacology text, Netter's Illustrated Pharmacology, which received the top honor for an illustrated medical text from the Association of Medical Illustrators in 2005. He is active in several professional societies and is a regular reviewer for a number of scientific journals, including the Journal of Pharmacological and Experimental Therapeutics, European Journal of Pharmacology, and Neuropharmacology.

Tony DiBenedetto

New product marketing




Professor of Marketing at Temple University’s Fox School of Business, has been named among the top researchers worldwide for innovation management.

The International Association of Management of Technology (IAMOT) recently recognized Tony as one of the top 50 authors of technology and innovation management over the last five years, based on a quantitative analysis of research from 2003-2007. This exceptional achievement places Tony among the top one percent of all researchers in the field. He will be presented with a formal award at this year’s annual IAMOT conference, being held in April in Orlando.

Tony, an authority in product development and management, teaches in the Fox School’s MBA and Executive MBA programs and has also served as director of the International Business Summer Program at Temple’s Rome, Italy campus.

In his most recent research studies, Tony has examined managerial perceptions of global first-mover advantage, the competitive advantage of new ventures with innovative new products and services, the use of knowledge for product innovation performance, the effects of manufacturer-distributor and manufacturer-supplier cooperation, and the effects of marketing and technology capabilities on strategic type.

Tony has been Editor-in-Chief of the Journal of Product Innovation Management since 2004, and is co-author of the leading product innovation textbook, New Products Management, currently in its ninth edition. He is a certified New Product Development Professional (NPDP).

In 2007, Tony was ranked among the world’s top scholars in innovation management, according to a study in the Journal of Product Innovation Management (Vol. 24, No. 3, 2007). He was named a Washburn Senior Research Fellow in 2007 and has been named to the Fox School’s Dean’s Research Honor Roll multiple times.

Tony’s research interests include new product development and launch, new product strategy, global new product development and technology entrepreneurship. He is listed in Marquis Who’s Who in America and Marquis Who’s Who in the World.


Di Benedetto is Professor of Marketing at Temple University, Philadelphia, PA. He holds a Ph. D. degree in Administration, an M.B.A., and a B. Sc. degree in Chemistry, all from McGill University, Montreal, Canada. He taught at the Universite du Quebec a Montreal and the University of Kentuckybefore moving to Philadelphia in 1990. Since arriving at Temple he has taught predominantly in the night M.B.A. program and also in Temple'sExecutive M.B.A. and International M.B.A. programs. He has taught Marketing in Temple's International Business Summer Program at the Temple Romecampus in Italy since 1992. He is a recipient of Temple University's Great Teacher Award, the Lindback Award for teaching excellence, a Department of Marketing teaching award, and the Lynne A. Cronfeld Research Award/Grant.

Prof. Di Benedetto has been published in the Journal of Product Innovation Management, Management Science, Strategic Management Journal, Journal of International Business Studies, IEEE Transactions on Engineering Management, Journal of Business Research, Columbia Journal of World Business, Industrial Marketing Management, Interfaces, Journal of Advertising Research, and elsewhere, primarily in the areas of new product development and industrial marketing management and strategy. He has been named to the Dean's Research Honor Roll of the School of Business and Management.

Prof. Di Benedetto is co-author with Merle Crawford on New Products Management, published by Irwin/McGraw-Hill. He has also co-authored a book on industrial product innovation and a computer-supported casebook in new product development. As a freelance consultant, he has carried out marketing and economics studies for private companies and government agencies in the Montreal, Lexington (Kentucky) and Philadelphia areas.

Prof. Di Benedetto is a certified New Product Development Professional (NPDP). He is the Editor of the Journal of Product Innovation Management. In the past, he has served as Vice-President of Publications for the Product Development & Management Association (PDMA), as Editor of Visions, the national newsletter of the PDMA, as a member of the Board of Directors of the PDMA, as Abstracts Editor of the Journal of Product Innovation Management and as Treasurer of the Philadelphia Chapter of the American Marketing Association. Prof. Di Benedetto is listed in Marquis Who's Who in the World and Marquis Who's Who in America.

Ellen Walker

Clearing the fog; 

Researcher gets $1.5 million dollar grant to examine side effect of chemotherapy 

Many of the side effects from chemotherapy are well documented: Fatigue, nausea and hair and weight loss. But there is another one that has split the medical community about whether is even exists. It's called chemotherapy-induced cognitive deficits or “chemo fog” and pharmacologist Ellen Walker hopes her research not only proves its real, but finds the cause. 

Walker, a PhD and associate professor of pharmacodynamics at the School of Pharmacy, received a $1.5 million dollar National Institutes of Health grant at the beginning of this year to study the possible effects of drugs used during chemotherapy on cognitive impairment. It’s a big grant, with perhaps even bigåger implications for how researchers and patients deal with chemotherapy-induced cognitive deficits, which chemotherapy patients liken to being in a fog, as if they’re brain isn’t working right. Misplaced items, inability to multi-task, short-term memory loss are hallmarks of the condition. And while there is clinical evidence to support its existence, research studies on the topic are scant. 

“My colleague Bob Raffa and I were stunned at the lack of published literature, considering cancer patients have been getting chemotherapy for nearly 50 years,” said Walker. “Most studies have looked at how well chemotherapeutic agents kill the tumor, not if they cause a cognitive deficiency, like memory loss.” 

Walker and Raffa decided to fill that void. Two years ago, Walker and PharmD student John Foley, set out to see if certain chemotherapeutic agents caused memory and learning deficits in mice. They tested two older drugs commonly used to treat breast cancer, a cancer with recently higher survival rates whose survivors have dominated the limited clinical research on chemotherapy-induced cognitive deficits. They suspected the drugs, methotrexate and 5-fluorouracil, weren’t toxic alone, but when given together, could cause deficits. Six months into their research, their hunch proved right. 

“Alone, methotrexate didn’t cause learning or recall deficits in mice when given once. Mice given 5-flurouracil once showed some deficits in recall, but when we gave the mice both drugs, it had a synergistically worse effect on their ability to learn and remember.” 

In other words, the mice forgot what they learned a day after being given the chemotherapeutic agents. And as Walker expanded their research, giving the drugs once a week for three weeks, they saw even more deficits than just giving it acutely. Armed with their results, this one-time side project became a priority. What followed were months of research and the involvement of more colleagues to help define better dose combinations and regimens. But there was also the ping-pong of NIH reviews and revisions to endure and Walker and her research team had run out of money. In March, 2008, a $50,000 bridge grant through the Office of Research and Strategic Initiatives allowed her research to continue. 

Eight months later, the NIH sent word that they were not only funding Walker’s research with a five year, $1.5 million dollar grant, but she received a priority percentile ranking of 0.8, placing it at or very near the top of all peer applications. 

“I had to look at the score twice because I couldn’t believe it,” said Walker. 

It wasn’t just Walker who was impressed by the score. 

“I was delighted to learn about the grant and its truly outstanding ranking,” said Larry F. Lemanski, Ph.D., Senior Vice President for Research and Strategic Initiatives at Temple.  “This major grant from the National Institutes of Health will allow Dr. Walker to significantly expand her research programs. At the same time, the award will increase Temple’s reputation as a major player in this very important field of biomedical research.” 

Indeed the funding will allow Walker to triple her efforts. She can put someone full-time on the project and study four more chemotherapeutic agents. And down the road, she would like to figure out how to protect the brain before chemotherapy to prevent chemo fog. 

For now, there is still controversy surrounding chemo fog, as clinicians and scientists debate if the disease itself or the drugs to fight cancer cause it. Other culprits could include genetics, hormone inhibitors, anemia and early-onset menopause. Instead of a natural onset, chemotherapy often catapults women into menopause, potentially leaving them fuzzy-minded. And there are those who doubt chemo fog is real. Walker believes it is. She recalls how during her mother’s battle with breast cancer, she put a chicken still covered in plastic wrapping in the oven for dinner. 

“It seemed like she wasn’t always thinking clearly even after her chemotherapy was over. I always wondered was it the psychological stress of cancer, the chemotherapy, or some other side effect of the many medications she received.” 

Ellen Walker may well be on her way to finding the answer. 

Jennifer Cromley

Jennifer Cromley, assistant professor of educational
psychology in the College of Education, is developing and
testing new instructional techniques aimed at teaching
high-school science students how to use the diagrams that
appear in their biology textbooks.

Research from a range of disciplines has shown that people
have difficulty making sense of diagrams. The investigators
had previously found that inference and other high-level
processes that are important for learning from text are even
more important for learning from diagrams. They further showed
that students who use textbook diagrams the least show the
smallest gains in content understanding from the textbook.

The investigators will capitalize on commonalities among
several theories of diagrammatic reasoning to develop four
interventions, following an additive design, aimed at
improving classroom instruction in how to use diagrams. In
each iteration, one additional intervention feature is added
to the initial intervention.

In the first intervention, they will teach the components of
diagrams (i.e., how to read captions, color keys, and other
conventions of diagrams). In the second, they will also teach
the coordinating of text and diagrams. In the third, they will
also have the students engage in self-explanation. In the
fourth, they will also have students construct their own
drawings.

In conjunction with these experimental studies, the
investigators will collect eye tracking data on a subset of
participants pre- and post-intervention in order to look for
possible changes in gaze patterns.

Joanna Maselko

Joanna Maselko (Public Health), a social and psychiatric epidemiologist who researches the socioeconomic determinants of mental health in the global context, and the relationship between religious engagement/spirituality and health, recently received a grant from the John Templeton Foundation for the project, “Stress, Violence and Spiritual Capital" and a grant from the National Institutes of Health. Maselko has done interesting work on the relationship between religious belief and mental health. There seems to be some kind of correlation between belief and sanity, but Maselko is quick to point out that one can't infer a causal relationship. A factor in her work is that it is meta-research: she is not gathering new data, but rather using longitudinal data, of which the collection began 40 years ago, and for a very different purpose. Hers is the first longitudinal study of religion and mental health. Some of work centers on the sociological concept of "social capital" and its relation to mental health. This work is funded by the Templeton Foundation, which she reports makes her work somewhat suspect to some scientists. She feels that this source of funding is accepted without prejudice at Temple; this open-mindedness is one reason that she came to Temple, when she might have gone to a school that has a college of public health.



Currently, Dr. Maselko is conducting research on the social determinants of mental health in international settings. Of particular interest is the link between economic development and mental health in developing countries, especially in South Asia. Economic development is often associated with changes that impact family and social networks and supports, which might have adverse effects on mental health. On the other hand, increased economic opportunities are associated with improved health and well-being and Dr. Maselko hopes to elucidate the aspects of economic and social development that are salient to health. She has conducted research on women’s empowerment in Bangladesh, socioeconomic disadvantage and suicide in Goa, India, and is currently conducting a study exploring the connections between negative life events, debt, spiritual coping and mental health in Karnataka, India.



Dr. Maselko also conducts studies on the role of individual’s changing levels of religious engagement over the lifecourse in the development of psychopathology. She is especially interested in how gender and socioeconomic status impacts the relationship between religious engagement/spirituality and health, with a special focus on diverse religious environments. For example, findings from this line of research suggest that denominational differences in the strength of the association between religious engagement and psychological health between men and women. Ongoing projects explore the role of religious institutions in shaping the religion-health connection.



Women who stop being religiously active are three times more likely to suffer generalized anxiety disorder than women who have always been religiously active, researchers report.



"One's lifetime pattern of religious service attendance can be related to psychiatric illness," she said. Maselko and her team analyzed data from 718 adults who shared details of their religious activity in youth and adulthood. They found that a majority of the respondents changed their level of religious activity between childhood and adulthood. The data is published in the January issue of Social Psychiatry and Psychiatric Epidemiology.



According to Maselko, the gender differences in the relationship between religious participation and mental health may be tied to social networks. Women are more likely to build them through their religious activities, and then to feel the loss of those networks when they stop attending church, she explained.



Slightly more than one-third of the women reported always being religiously active. Half said they had not been active since childhood. About 7 percent of the women who were always religiously active could be categorized as having generalized anxiety disorder, compared with 21 percent of those who had ended their religious activities.



People with generalized anxiety disorder experience worries and concerns out of proportion to their daily lives, according to the National Institute of Mental Health. The disorder is diagnosed if the worries do not abate after six months. About 6.8 million Americans suffer from the disorder, which can seriously interfere with sleep and relaxation. Women are two times more likely to suffer from anxiety disorder than men.



"Everyone has some spirituality, whether it is an active part of their life or not; whether they are agnostic or atheist or just 'non-practicing.' These choices potentially have health implications, similar to the way that one's social networks do," Maselko said.