January 2007 | VOL. 6, NO. 1 | www.McGowan.pitt.edu

Nicholas Peppas, Sc.D., Fletcher Pratt Chair of Chemical Engineering, Biomedical Engineering and Pharmaceutics at the University of Texas at Austin will deliver the next McGowan Institute Distinguished Lecture on February 8, 2007. His topic is: Nanostructured Biomaterials and Surfaces for Biological Recognition.

The McGowan Institute Distinguished Lecture Series highlights the research of some of the nation’s most gifted, creative, and innovative scientists whose work will hold great interest for McGowan Institute Faculty. In addition to providing the opportunity to showcase their pioneering work here, these lectures also provide an opportunity for these distinguished guests to meet with some of our own preeminent scientists. We all recognize that great science does not occur in a vacuum and the networking and possible collaboration that these visits offer is of benefit to all of the participants.

The inaugural lecture was given by Art Coury, Ph.D., Vice President Biomaterials Research-Genzyme. His topic was “Tissue Engineering, Regenerative Medicine: Perceptions, Realities and Implications.”

We encourage you to participate in the lecture series, and to have your trainees and staff to attend as well. If you have an interest in personally meeting with any of the lecturers, please contact Lindsay Lawry (lawryle@upmc.edu or 412-235-5117) so that we can work to accommodate all interested faculty in the itinerary for each guest.

All of the lectures, which are free and open to the public, will take place at 4 PM on the designated day in the Public Health Auditorium, Parren Hall.

February 8th – Nicholas Peppas, Sc.D.

• Fletcher Pratt Chair of Chemical Engineering, Biomedical Engineering and Pharmaceutics at the University of Texas at Austin
• Director of Center on Biomaterials, Drug Delivery, Bionanotechnology and Molecular Recognition
• Director of National Science Foundation Program on Cellular and Molecular Imaging for Diagnostics and Therapeutics

Topic: Nanostructured biomaterials and surfaces for biological recognition
Abstract: Engineering the molecular design of intelligent biomaterials by controlling recognition and specificity is the first step in coordinating and duplicating complex biological and physiological processes. We address design and synthesis characteristics of artificial molecular structures capable of specific molecular recognition of biological molecules. Molecular imprinting and microimprinting techniques, which create stereo-specific three-dimensional binding cavities based on a biological compound of interest, can lead to preparation of biomimetic materials for intelligent drug delivery, drug targeting, and tissue engineering. We have been successful in synthesizing novel glucose- and protein-binding molecules based on non-covalent directed interactions formed via molecular imprinting techniques within aqueous media.
Location: Graduate School of Public Health, 130 Desoto Street, Room G23
Time: 4:00 to 5:00 PM

For Additional Information, please click here

McGowan Institute - 2007 Scientific Retreat
Nemacolin Woodlands Resort - Farmington, PA
March 5 and 6, 2007

Registration Deadline: February 1st
On-Line Registration and Program

It is estimated that nearly 21 million people in the United States have diabetes. Further, there are dire predictions of a dramatic increase in the incidence of newly diagnosed cases in the near future.

The complications of diabetes include heart disease, stroke, high blood pressure, blindness, kidney disease, nervous system disease, and amputations (more than 60% of non-traumatic lower-limb amputations in the United States occur among people with diabetes). Estimates of the cost of diabetes in the United States (direct and indirect) are ~$132 billion cholesterol and blood pressure.

Two concurrent studies at the University of Pittsburgh continue to make impressive strides in the field of diabetes prevention and treatment, the results of which offer promise in the future for diabetes patients and their families.

McGowan Institute faculty member Dr. Massimo Trucco (picture right) and his research team have successfully reversed Type I Diabetes in animals by injecting the animals' own harvested dendritic cells, which allow the pancreas to resume insulin production. A clinical trial of this pioneering therapy is underway involving at least 15 patients over the age of 18, with Type 1 diabetes. Read more

The work of Dr. William M. Ridgway's team that is investigating the prevention of Type 1 diabetes was reported in the January 2007 issue of Diabetes, the journal of the American Diabetes Association. The report profiles the successful trials into preventing Type I diabetes in mice using antibody injections targeting receptor CD137. His investigation suggests that this type of therapy may one day work on people who are genetically predisposed to insulin-dependent diabetes. Read more

Research Highlights

John A. Kellum, MD, associate professor of critical care medicine in the School of Medicine, has received a grant from the National Institutes of Health to explore the mechanism responsible for recovery from kidney failure. The grant is a five-year, $1.8 million award from the National Institute of Diabetes and Digestive and Kidney Diseases for research that will shed light on the role of inflammation, as well as other factors in recovery from acute renal failure (ARF).

The project, called Biological Markers of Recovery for the Kidney, or BioMaRK, will examine how such factors influence survival as well as recovery of kidney function. The researchers plan to assess how certain inflammation markers relate to clinical outcomes and build a risk-prediction model based on clinical variables and those biomarkers. The results of this study could lay the foundation for the development of ARF treatment therapies, particularly those designed to enhance organ recovery. MORE

A study led by Augustine Choi, M.D., professor of medicine and the chief of the division of pulmonary, allergy and critical care medicine has demonstrated that low-dose carbon monoxide administered in conjunction with oxygen therapy markedly inhibits oxygen-induced damage to lung cells. These findings, being reported in the Jan. 19 issue of the Journal of Biological Chemistry, have significant implications for the treatment of acute respiratory distress syndrome, or ARDS, according to the study’s authors.

ARDS is a life-threatening medical condition in which patients experience severe shortness of breath and oxygen starvation. Although ARDS often occurs in people who have lung disease, even people with normal lungs can develop the condition as the result of severe trauma or an infection. Without prompt treatment, the oxygen deprivation resulting from ARDS can be lethal. Even with appropriate treatment, however, about 30 to 40 percent of all people with severe ARDS die from the condition. In fact, it is the number one killer of patients in intensive care unit facilities in the United States.

Based on previous research showing that low-dose carbon monoxide (CO) has potent anti-inflammatory effects in a number of tissues, the Dr. Choi and his colleagues cultured lung cells from mice in a medium with a high concentration of oxygen, with and without low levels of CO. They then monitored the cells for hyperoxia-induced toxicity.

According to the investigators, these results suggest that CO may expand the currently limited therapeutic options for treating ARDS. MORE

The Russell Laboratory, in collaboration with the polymer experts at the Institute has developed a hairy polymer surface that causes mold's filaments, known as mycelia, to explode before they produce spores.

The method reduces to a basic biophysical process: The hairy polymer carries a positive charge. After a few intermediate processes, the negatively charged mold couples like a magnet with the positively charged polymer. That's when the polymer's spray of ions pops open the membrane of the mold's mycelia, making it impossible to produce spores.

To date, the research team has produced two types of mold-popping polymers. One repels water and the other is water soluble. Both restrict spore production in a battle of filaments: polymer hairs vs. mycelia.

The research was funded by the University’s The Mascaro Sustainability Institute (MSI), who is currently seeking commercial partners to bung this innovative solution to market. MORE

The Regenerative Medicine Podcasts continue to be well received. There have been nearly 6,500 downloads to date. The most recent podcasts are:

#24- Alan Russell, PhD
As Regenerative Medicine Today celebrates its first anniversary, we welcome back our first guest from December 2005: Dr. Alan Russell, director of the McGowan Institute for Regenerative Medicine.
As a pioneer of and expert in regenerative medicine, Dr. Russell is well qualified to comment on the status and future of this fascinating and rapidly emerging field. In this podcast, Dr. Russell addresses:

• the history of the emergence of regenerative medicine, from over-hyped laboratory results, to failed medical devices, to successful clinical applications;
• the role of governments in the advancing the state-of- the-art and the clinical use of regenerative medicine technologies;
• initiatives to assist soldiers (and, ultimately, the civilian population) who have suffered massive loss of tissue due to trauma, and;
• the status of the professional society that serves the scientists who are developing regenerative medicine technologies.

#25- Yoram Vodovotz, PhD
Most of us view inflammation in our bodies as something to avoid at all cost. Severe inflammatory situations such as sepsis, also known as systemic inflammatory response syndrome (SIRS), is a serious medical condition caused by the body's response to an infection. Sepsis can lead to organ failure, gangrene, and even death.

Clearly inflammation has a bad rap... but some inflammation can be good. It is essential to the healing process, and it is essential to understand inflammation to predict how drugs (new and proposed) impact healing.

In today's podcast, Dr. Yoram Vodovotz discusses the research that he and his colleagues are pursuing to model inflammatory responses in the body. They have used these models to successfully predict the outcomes of drug trials.

#26- Robert Eberhart, PhD
Many of our listeners are familiar with intravascular stents, a commonly used tool to help treat coronary artery disease. The stents used today are metallic, and some of the stents are coated to reduce the post-implant complications of this "foreign" device being inserted in the body.

In today's podcast, Dr. Robert Eberhart discusses the research that he and his colleagues are pursuing to bring to clinical practice a radically different design of an intravascular stent. Dr. Eberhart is a Professor, Department of Engineering in Surgery, University of Texas Southwestern.

The device that has been developed in the Eberhart Labs is a bioresorbable poly-(L-lactic Acid) stent that is porous enough so that drugs can be implanted in the stent (see illustration at the right) and slowly released over an extended period of time.

Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.

Based on the requests of faculty and graduate students for more and different types of networking sessions, the Moleculart project continues.  Our goal is to have a scientific gathering that fosters networking in a different environment. The next session will be in on April 9, 2007, featuring artist Penny Oliver, wife of Chris Oliver, MD. More

 

Authors:	Xue Wang, Yong Wang, Hong Pyo Kim, Kiichi Nakahira, Stefan W. Ryter, and Augustine M. K. Choi
Title:	Carbon Monoxide Protects against Hyperoxia-induced Endothelial Cell Apoptosis by Inhibiting Reactive Oxygen Species Formation
Summary:	Hyperoxia causes cell injury and death associated with reactive oxygen species formation and inflammatory responses. Recent studies show that hyperoxia-induced cell death involves apoptosis, necrosis, or mixed phenotypes depending on cell type, although the underlying mechanisms remain unclear. Using murine lung endothelial cells, we found that hyperoxia caused cell death by apoptosis involving both extrinsic (Fas-dependent) and intrinsic (mitochondria-dependent) pathways. Hyperoxia-dependent activation of the extrinsic apoptosis pathway and formation of the death-inducing signaling complex required NADPH oxidase-dependent reactive oxygen species production, because this process was attenuated by chemical inhibition, as well as by genetic deletion of the p47phox subunit, of the oxidase. Overexpression of heme oxygenase-1 prevented hyperoxia-induced cell death and cytochrome c release. Likewise, carbon monoxide, at low concentrations, markedly inhibited hyperoxia-induced endothelial cell death by inhibiting cytochrome c release and caspase-9/3 activation. Carbon monoxide, by attenuating hyperoxia-induced reactive oxygen species production, inhibited extrinsic apoptosis signaling initiated by death-inducing signal complex trafficking from the Golgi apparatus to the plasma membrane and downstream activation of caspase-8. We also found that carbon monoxide inhibited the hyperoxia-induced activation of Bcl-2-related proteins involved in both intrinsic and extrinsic apoptotic signaling. Carbon monoxide inhibited the activation of Bid and the expression and mitochondrial translocation of Bax, whereas promoted Bcl-XL/Bax interaction and increased Bad phosphorylation. We also show that carbon monoxide promoted an interaction of heme oxygenase-1 with Bax. These results define novel mechanisms underlying the antiapoptotic effects of carbon monoxide during hyperoxic stress.
Source:	J. Biol. Chem., Jan 2007; 282: 1718 - 1726

 

PIs:	John A. Kellum, MD
Title:	Biological Markers of Recovery for the Kidney (BioMaRK)
Description:	Investigate the role of inflammation, as well as other factors in recovery from acute renal failure (ARF). This project, called Biological Markers of Recovery for the Kidney, or BioMaRK, will examine how such factors influence survival as well as recovery of kidney function. The study will assess how certain inflammation markers relate to clinical outcomes and build a risk-prediction model based on clinical variables and those biomarkers. The results of this study could potentially lay the foundation for the development of ARF treatment therapies, particularly those designed to enhance organ recovery.
Source:	NIH- National Institute of Diabetes and Digestive and Kidney Diseases
Term:	5 Years

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