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Stimulus Act Money Funds Two Grants

Almost half a million dollars of the American Recovery and Reinvestment Act (ARRA) of 2009, aka the Stimulus Bill, is finding its way to the University thanks to two recent grants in pharmaceutical sciences from the National Institutes of Health (NIH).

 

“The funding of these two applications is extremely important to our department.  First, important health research questions will be addressed, from how compounds cause liver damage to how to selectively deliver drugs to kill cancer cells while minimizing damage to normal ones. These studies could lead to improved health care for us all,” said Dr. Adeboye Adejare, chair of pharmaceutical sciences. “In the meantime, they will provide training in research methods to some of our students. They will also provide summer employment opportunities for students and faculty. This is a very efficient and effective use of ARRA funding.”

 

Dr. Charles N. McEwenDr. Peter Harvison, a professor in the department, will use his grant money for a study on “Thiazolidinedione-induced Hepatotoxicity.” As outlined in the project relevance section, the 2,4-thiazolidinedione (TZD) ring, found in current and prototype drugs, may be a factor in hepatotoxicity (liver damage) in some patients who take these therapeutic agents. This project is designed to develop an in vitro, non-animal based system to investigate the relationship between TZD rings and hepatotoxicity. An understanding of this connection may lead to development of better and safer drugs that contain TZD rings.

 

Dr. Charles N. McEwenAlso in pharmaceutical sciences, Dr. Clyde Ofner’s grant will focus on “A Biodegradable Doxorubicin Conjugate for Enhanced Tumor Uptake and Efficacy.” Ofner, who is an associate professor and director of the graduate pharmaceutics program working with anticancer drugs, aims to see if his biodegradable delivery system will localize the drug to tumors “for greater anti-tumor effects and reduce toxic, life-threatening, side effects of the drug. If the aims and goals of this proposal are achieved, the feasibility of this system will be established with good prospects for therapeutic advantages of tumor treatment and reduced systemic toxicity in clinical practice for doxorubicin as well as for other anti-tumor drugs.”

The Department of Health and Human Services notes: “The recent ARRA legislation provides an unprecedented level of funding ($8.2 billion in extramural funding) to the NIH to help stimulate the U.S. economy through the support and advancement of scientific research. While NIH Institutes and Centers have broad flexibility to invest in many types of grant programs, they will follow the spirit of the ARRA by funding projects that will stimulate the economy, create or retain jobs, and have the potential for making scientific progress in two years.”


Written By:  Brian Kirschner
Contact:  Brian Kirschner
Contact Email:  b.kirschner@usp.edu
Contact Phone:  215.895.1186

 

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Governor Rendell Awards KISK Grant to University of the Sciences

On March 16, Governor Edward G. Rendell announced that University of the Sciences in Philadelphia has been awarded a $150,000 grant from the Keystone Innovation Starter Kit (KISK) program.

University of the Sciences joins 17 other colleges, universities, academic medical institutions, and research institutions from across the state that will receive a portion of the $2.5 million investment from the KISK program.

The KISK initiative is designed to recruit top faculty researchers in crucial advanced knowledge areas to universities throughout Pennsylvania. Governor Rendell said the investment will help local economies, serve as a driver for the commonwealth’s economic growth, and help to cement Pennsylvania’s reputation as a world-class leader faculty recruitment and advanced technology.

The University’s grant will be managed by Dr. John Porter, professor of biology and research professor of pharmacognosy.

“The award to University of the Sciences will foster the marriage between two of our core strengths: natural products chemistry and molecular biological applications in biotechnology,” said Dr. Porter. “The faculty member that we are recruiting will have strengths and research that combines these two areas as we continue to develop the educational and research opportunities in which the Department of Biological Sciences is active.”

Dr. Porter explains that the grant monies will allow the purchase of specialized equipment and software that will strengthen the ability to produce natural products from engineered microorganisms, make analytical separations method development more efficient, and analyze the products generated. This equipment will also be a resource to regional companies with which the University partners for development of new therapeutics based on natural product lead compounds.

Written By:  Marisa Olson
Contact:  Marisa Olson
Contact Email:  m.olson@usp.edu
Contact Phone:  215.596.8788

 

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Taking Aim at Tumors with Magic Bullets

Dr. Charles N. McEwenThe future of anti-cancer drugs may one day work like a laser-guided missile that hones in on its target. But if the missile misses, instead of harming good organs and tissues, the drug will simply break apart and be safely excreted from the body.

This “Magic Bullet” approach is the hope of researcher Dr. Clyde Ofner III from the department of Pharmaceutical Sciences and Director of the Graduate Program in Pharmaceutics who is one of the early researchers in an emerging field of antineoplastic agents.

(Above: Dr. Clyde Ofner III)

Dr. Ofner recently returned from Nuremberg, Germany, where he was invited to share his research on gelatin-methotrexate conjugates with the international scientific community at the EHRLICH II -- 2nd World Conference on Magic Bullets that took place from October 3-5. The conference is named after Paul Ehrlich, who is recognized for coining the term "Magic Bullets" and presented his ideas about chemotherapy at his Nobel talk 100 years ago. The first conference was held in 2004.





(Diagram: A "Magic Bullet" will exploit the advantage of poor cellular junctions in tumors to build up in a passive accumulation but avoid healthy tissues.)

“The reason we say ‘magic’ is because medicine doesn’t work that way,” said Dr. Ofner. “All medicines have side effects, especially cancer drugs. Some people die from the drug before the drug can kill off the cancer. In fact, most anti-cancer drugs are poisons.”

Through macro molecular conjugate drug delivery, Dr. Ofner is researching whether drugs can be safely targeted at tumors in a passive manner that uses the body’s processes. This is different from a more common approach that uses molecules attached to the drugs to bind and, therefore, target structures found on cancer cells.

“The idea with macro molecular conjugate drug delivery is not only to tinker with the cancer cells, but to also influence the body,” Dr. Ofner explained.

Dr. Ofner has three stages of drug design for these conjugates. He was assisted by three former graduate students Bill Bowman PhD’01, Chao-Shen Cheng PhD’05 and Karen Pica PhD’05, who did research in the first two stages, and with current graduate and undergraduate students, is now embarking on studies of the third.

In the first stage, the drug and its carrier are designed to circulate in the body for longer than normal times. By using a high molecular weight and longer circulation, the entire conjugate has an opportunity to zero in on solid tumors by taking advantage of poor cellular junctions in tumors to build up in a passive accumulation but avoid healthy tissues. The mechanism is based on what’s called the Enhanced Permeability and Retention (EPR) effect.

“There are two big potential pluses with being able to use a high molecular weight,” Dr. Ofner said. “We believe we will be able to target drug delivery and minimize side effects.”

The second stage is what makes Dr. Ofner’s research exciting--the potential for the antineoplastic agent to biodegrade if it does not find a tumor and avoid toxicities observed with other macro molecular carriers under investigation and avoid toxicities of the anti-cancer drug.

“We use a biodegradable carrier. Most researchers have taken the approach of using synthetic polymers, but they don’t get broken down by the body,” Ofner said. “Those models also have to keep a lower size to be filtered out through the kidneys. We are using a much higher molecular weight and the higher the size you use, the more we anticipate will build up in the tumor.”

The final stage of design will explore the bond between the drug and the carrier. His recent research has shown that a new bond is needed because the link was too strong and did not effectively release the drug. In the last year or two, Dr. Ofner and graduate students Brian Rhodes and Darren Wu are now exploring the use of an acid cleavable conjugate bond.

“We always had the first two parts,” he said. “We are now moving on with selective pH release. The drug is not expected to release in the blood stream because it has neutral pH. Instead, when it gets into the tumor there is a slightly acidic pH that will cause the drug to be released.”

So far, his work has been in vitro using controlled pH and enzymes as well as cell cultures but plans are underway for animal studies.

Dr. Ofner works collaboratively on campus with Dr. Ruy Tchau and Dr. Bin Chen to utilize their pharmacology and toxicology backgrounds but who are also in the Department of Pharmaceutical Sciences. Despite being slated to speak and moderate a session at EHRLICH II in New/Known Targets and Mechanisms, Dr. Ofner says his work has been classified as drug delivery, experimental therapeutics, and even translational research. In any classification, it falls out of mainstream medical research.

“In general, there are a few labs doing research in macro molecular conjugate drug delivery. It started about 20 years ago and only three have been approved for market. A few others are in phase one, two, or three clinical trials. All but one are using synthetic polymers,” Dr. Ofner said. “We are one of only a couple labs that are conducting research on biodegradable anti-cancer drugs.”

Written By:
  Brian Kirschner
Contact:  Brian Kirschner
Contact Email:  b.kirschner@usp.edu
Contact Phone:  215.895.1186

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Visiting Researcher from Italy to Serve as 2008 Glasser Visiting Professor

Dr. Pier Giorgio RighettiWith a number of patented methodologies to his credit, Dr. Pier Giorgio Righetti of Milan’s Polytechnic Institute (Italy) has been invited to share his knowledge as the 2008 Glasser Visiting Professor. Dr. Righetti will conduct three lectures during his time on campus which runs from Saturday, October 25 through Friday, Oct. 31, including his public lecture, The ProteoMiner and the FortyNiners: Searching for Gold Nuggets in the Proteomic Arena, on Wednesday, October 29 from 4 to 6 p.m. in the McNeil STC.

Additionally, Dr. Righetti will be hosted by Chemistry Department on Monday, October 27 from 3 to 4 p.m. in PTC 140 with an address titled SDS-PAGE (the second dimension of 2D maps). He will also be the guest of Pharmaceutical Sciences on Tuesday, October 28 from 3-4 p.m. in PTC 131 lecturing on the subject of Isoelectric focusing and immobilized pH gradients: the long march towards the steady-state.

A reception will follow each of the lectures. All events are free and open to the public.

Professor Righetti earned his PhD in organic chemistry from the University of Pavia in 1965. He then spent three years as a post doc at MIT (Cambridge, Mass.) and one year at Harvard (Cambridge, Mass.). He is currently a full professor of biochemistry at the Milan’s Polytechnic (Italy). He has developed and patented a number of important methodologies, such as isoelectric focusing in immobilized pH gradients, multicompartment electrolyzers with isoelectric membranes, membrane-trapped enzyme reactors operating in an electric field, temperature-programmed capillary electrophoresis and, most recently, combinatorial ligand libraries (hexapeptide baits) for the capture and amplification of the low-abundance proteome. His research interests include protein purification and crystallization, screening for genetic defects, DNA-based diagnosis and proteomics. During his scientific career, he has published over 700 articles.

The Glasser Visiting Professor program is sponsored by a generous donation from Abraham Glasser P’43 and his wife, Gloria. The Glassers’ gift enables the University to invite a young, innovative scientist from Europe to interface with faculty and students and the surrounding scientific community. The Glassers hope such interactions will promote scholarly activity and collaborative efforts in the areas of biotechnology and molecular biology.

Written By:  Brian Kirschner
Contact:  Brian Kirschner
Contact Email:  b.kirschner@usp.edu
Contact Phone:  215.895.1186

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Glasser Visiting Professor Seminar Series,
October 28th, 3:00-4:00 p.m. & October 29th, 4:00 -6:00 p.m.

Dr. Pier Giorgio Righetti from Milan's Polytechnic Institute will be on campus from October 27th -October 31st.  During his visit, the Graduate Student Organization will sponsor some off-campus as well as on-campus events with Dr. Righetti.


Date: Tue, Oct 28, 2008
Time: 3:00 PM - 4:00 PM
Contact: Shanaz Tejani-Butt (s.tejani@usp.edu)
Phone: 215-596-8594
Location: Pharmacology-Toxicology Center PTC 131
Sponsor: College of Graduate Studies
Topic: "Isoelectric focusing and immobilized pH gradients: the long march towards the steady-state"
Hosted By: The Department of Pharmaceutical Sciences

 

Date: Wed, Oct 29, 2008
Time: 4:00 PM - 6:00 PM
Contact: Shanaz Tejani Butt (s.tejani@usp.edu)
Phone: 215-596-8594
Location: McNeil Science and Technology Center STC
Sponsor: College of Graduate Studies  
Topic: "The ProteoMiner and the FortyNiners: Search for Gold Nuggets in the Prosteomic Arena"
Hosted By: College of Graduate Studies

 

A reception will follow each of the lectures. All events are free and open to the public. 

Dr. Pier Giorgio Righetti has developed and patented a number of important methodologies and published over 700 articles in the fields of protein purification and crystallization, electrophoresis and proteomics.  

The Glasser Visiting Professor program enables the University to invite an innovative scientist from Europe to interface with faculty and students and the surrounding scientific community and promote scholarly activity and collaborative efforts in the areas of biotechnology and molecular biology. 

 

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Pharmacy Administration Students to Present at ISPOR Meeting in Toronto May 3-7

The following students in USP's Master of Science in Pharmacy Administration program will be presenting posters at the International Society for Pharmacoeconomics and Outcomes Research meeting, taking place in Toronto from May 3-7...

COST–EFFECTIVENESS ANALYSIS OF PEGAPTANIB (MACUGEN®) AS COMPARED WITH
RANIBIZUMAB (LUCENTIS®) FOR TREATING IN AGE–RELATED MACULAR DEGENERATION (AMD)

Lu L.Y. and McGhan W    
University of the Sciences in Philadelphia, PA, USA

COST-EFFECTIVENESS MODEL FOR SMOKING CESSATION THERAPY USING VARENICLINE
Viswanathan S, Neville W, Patel E, Raparla S, and McGhan WF 
University of the Sciences in Philadelphia, Philadelphia, PA, USA

COST-EFFECTIVENESS OF TNF-ALPHA INHIBITORS IN
COMPARISON TO OTHER STRATEGIES IN THE TREATMENT OF MODERATE-TO-SEVERE
PSORIASIS: A DECISION ANALYSIS MODEL

Viswanathan S and McGhan WF 
University of the Sciences in Philadelphia, Philadelphia, PA, USA

COST-EFFECTIVENESS OF DIFFERENT STRATEGIES FOR DIAGNOSIS OF DEEP VEIN THROMBOSIS.
Patel V. and McGhan WF
University of the Sciences in Philadelphia, Philadelphia, PA, USA

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Building Connections Between University City Keystone Innovation Zone

Kiz

This event is free, but you must register to attend For more information call 267-295-3295 or Click Here.


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NSF Approves Atomic Force Microscope Grant

8/29/2007 - The National Science Foundation (NSF) recently announced the funding of a Major Research Instrumentation proposal submitted by Dr. Eschenazi, Chair and Professor of the Department of Mathematics, Physics and Statistics, and PI of the grant, for the acquisition of a $ 233,000 Atomic Force Microscope facility at USP. The proposal involved a collaborative effort of faculty of various Departments including Dr. Baumstark (Biology), Dr. Bentzley (Chemistry), Dr. Li (Pharmaceutical Sciences) and Dr. Tchao (Pharmaceutical Sciences). Dr. Eschenazi, these faculty and their students will use the new instrumentation for cutting edge cross-disciplinary research. Other faculty may consider the use of the instrumentation for their projects. The AFM facility will be located in the Physics Research Laboratory in the McNeil STC building. The AFM facility will also be instrumental for the future development of a new USP program in Physics with biophysics and materials science tracks. (read more)

The Atomic Force Microscope (AFM) is an essential modern tool for imaging nanostructures—objects thousands of times smaller than the diameter of a hair—and for measuring the delicate forces between molecules. These forces play an important role in fundamental processes occurring in physical and biological systems. With the imaging capability of the AFM researchers will be able to investigate the physical properties of patterned nanostructures as a step toward developing the computer, biomedical and pharmaceutical technologies of tomorrow. The acquisition of the Atomic Force Microscope will help its investigators unravel the mechanisms by which molecules of various types interact with each other. Ultimately these studies will lead to a better understanding of how the viruses responsible for diseases such as hepatitis C, influenza and polio replicate, or create copies of themselves. These studies will also help in the comprehension of how small particles, such as contaminants in groundwater systems, move and assemble themselves into aggregates. AFM studies of the structures of microbial enzymes involved in antibiotic resistance will help the design and development of novel antibiotics against anthrax and other lethal infections. This facility will make it possible for many other investigations and projects which require the AFM’s powerful imaging and analysis capabilities.

In bringing together researchers from physics, biology, chemistry and pharmaceutical sciences the diverse uses of the AFM facility will help foster a strong interdisciplinary environment at USP and create opportunities to make advancements in the research and discoveries in these areas. It will also benefit the students at USP, who will become better educated as future scientists and professionals. The acquisition of this instrumentation will have a positive impact on the whole University.

If you need more information about the AFM facility,

Contact:

  Dr. Eschenazi   (215-596-8707)


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USP Graduate Students Defend Dissertations

John P. Borneman - Use and Prevalence of Complementary and Alternative Medicine (CAM) by Populations with Specific Needs: Patients with Cancer, Breast Cancer, Benign Prostatic Hyperplasia, and Asthma

Tina Chen - Opening the Gate to Cell Division: Phosphorylation of Wee1 by Cdk2

Rachel Graves Forcino - Characterization of Blended PLGA:PEG Scaffolds for Bone Regeneration Applications

Rebecca Ann Hardin - Cognitive and Executive Functioning in Children After Posterior Fossa Tumor Resectioning

Grant Wayne Heinicke - Investigating Drug Release from Cationic Polymethacrylate-Coated Diltiazem Particles

Jena Yuk-Ying Lau - Cell-Substrate Interaction and Cell Membrane Destabilization

Saltanat Najmi - Effect of Para-Aminophenol on Cytochrome c Release

Sarah D. Reeser - A Fundamental Mechanistic Study of the MALDI Desorption/Ionization Process Via the Analysis of DNA-Anthracycline Complexes

Kevin E. Renahan - Prevelance of Specific Cognitive and Psychiatric Comorbidities Among Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients Observed in Two U.S. Healthcare Claims Databases: The Significance of Analytical Rigor

Shengguo Sun - Part A: Syntheses of Non-Competitive NMDA Receptor Antagonists; Part B: Drug-Polymer Conjugates for Colon-Specific Drug Delivery

Diansong Zhou - Using Computational Modeling Techniques to Rationalize/Predict Metabolism and Inhibition Involved in CYP3A4

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USP Graduate Students presented posters at the AAPS annual meeting in San Diego, CA November 10th -15th

AAPS (American Association of Pharmaceutical Sciences) held their annual meeting in San Diego, CA on November 10th - 15th. USP graduate students and facutly from the Department of Pharmaceutical Sciences attended. Fouteen graduate students presented posters (see below for full list) at the meeting and Shengguo Sun was selected to participate in the 2007 AAPS Graduate Student Symposium in Drug Design and Discovery sponsored by Bristol-Myers Squibb where he made a podium presentation.

See below for a list of presentations.



PRESENTATIONS

Pharmaceutics
AAPS Meeting, San Diego, CA, 11/7/07 – 11/15/07

1. “Attachment and proliferation of human dermal fibroblasts on PLLA:PEG  membranes:  effect of PEG molecular weight”
V. Swaminathan and S. Jonnalagadda

2. “In Vitro Toxicity Studies of Novel Neuroprotective Agents”
N. Coleman, K. Meachem, and A. Adejare

3. “Discovery of a novel noncompetitive NMDA receptor antagonist”                  
S. Sun and A. Adejare

4. “Effect of Drying Methods and Humidity on Drug Release and Determination of Kinetics of Water Release from Methyl Cellulose Microcrystalline Cellulose Bead System”
G. Shelukar  and R. Wigent

5. “Study of Ion Trap Mobility Spectrometry (ITMS) as a PAT Application”
E. Torres and Pardeep Gupta

6. “Synthesis and characterization of glutaraldehyde linked Insulin-TATPTD conjugate”
C. Hsiung and P. Gupta


7. “Preliminary synthesis and characterization of a novel gel doxorubicin conjugate with acid sensitive release”
B. Rhodes and C. M. Ofner III


8. “Amphiphilic Peptide Mediated Gene Transfer to Hepatoeytes”
X. Cui, G. Goparaju, S. Chandran and P. A. Gupta


9. “Evaluation of microsphere processing techniques on the physical and chemical stability of infliximab”     
K. Gokhale and S. Jonnalagadda


10. “Cytostatic and Cytocidal effects of a Gelatin-Methotrexat conjugate and free Methotrexate on HL60 Leukemia cells”
R. Desai, N. Patel, C. Chen, and C. M. Ofner III


11. “Fluorescence Studies of the Interaction of Recombinant Human Growth Hormone (r-hGH) to Polystyrene Nano-particles”
P. Desai and P. Gupta


12. “The effects of maternal low protein diets during pregnancy and lactation on the activity of hepatic cytochrome P-450 1A/2 in the offspring”
E. Yablonski, G. Cherala, and A. D’mello


13. “The Effect of PEG pm the Degradation of PLGA Scaffolds”
R. G. Forcino and S. Jonnalagadda


14. “Physical characterization of implants designed from polycaprolactone-poly- lacatide copolymers”
V. Waknis and S. Jonnalagadda


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