It gives me great pleasure to report on biomedical engineering at UCSD. The Institute of Biomedical Engineering and the Department of Bioengineering are at an exciting time witnessing rapid growth and advancement. The planning of the new Bioengineering Building, The Powell-Focht Building, is progressing smoothly (please see drawing below). A ground-breaking ceremony for the building will take place in the afternoon of August 9, 2000, on Pryatel Field where the building will be constructed.

We honor the legacy of Dr. B.W. Zweifach through the naming of the new Bioengineering Building’s library. The Zweifach Library will be located on the 4^th floor of the Powell-Focht Bioengineering Building (p. 4). We thank many of you who have generously contributed to the Y.C. Fung Auditorium fund raising goal, led by Drs. Ernest and Sue Huang. The matching goal is almost reached.

The Department of Bioengineering was ranked 3^rd in the nation by the U.S. News & World Report annual survey system (p 8). The Irwin and Joan Jacobs School of Engineering was ranked 15th in the nation for engineering schools. The Jacobs School was also 9th among public universities and 2nd in the University of California system.

UCSD was one of 18 schools selected out of 76 applicants to receive a Beckman Scholars award for Undergraduate Research. The UCSD proposal was a joint one among Bioengineering, Biology, and Chemistry (p 8). Our students continue to gain new awards and honors (p. 6). Two of the four UCSD students chosen for the prestigious Beckman Scholars award were from the Department of Bioengineering.

On April 18, 2000, Dr. Ferid Murad, the 1998 Nobel Laureate in Medicine, delivered the First Benjamin W. Zweifach Memorial Lecture. The lecture was a great success with many attendees from the Department, Institute and Medical School (p. 7).

As the academic year approaches its end in another month, I wish everyone a happy spring and summer.

-Shu Chien, Director, WIBE

 

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Profile of WIBE Industrial Affiliate

Background

The loss or failure of an organ or tissue is one of the most frequent, devastating, and costly problems in health care. Every year, millions of Americans suffer tissue loss or end-stage organ failure. Transplantation is severely limited by a critical donor shortage. Advanced Tissue Sciences, Inc., a leader in tissue engineering, has developed a proprietary core technology to manufacture human-based tissues and organs to help meet these needs. This unique human-based approach offers many benefits: products are physiological human tissues rather than simply cells or scaffolds; they are extensively tested
 
 

for safety; products are easy to use and available off-the-shelf. Few areas of technology will require more interdisciplinary research and innovative design than tissue engineering or have the potential to affect more positively the quality and length of life.
 
 

Multiple Products

The Company's first therapeutic products are tissue-engineered skin products: TransCyte^TM for the treatment of second and third-degree burns and Dermagraft® for diabetic foot ulcers. These skin products were developed from one cell type, fibroblasts, which can be used in the development of a variety of other product lines. Fibroblasts may also be useful in promoting angiogenesis and in other cardiovascular products. Similarly, Advanced Tissue Sciences is developing tissue-engineered cartilage using chondrocytes to explore a variety of orthopedic and reconstructive applications. Leveraging their expertise in tissue engineering, the Company experiences economies of scale and reduced learning curves in research, manufacturing, clinical and regulatory efforts.

Product Pipeline

The goal of Advanced Tissue Sciences is to develop an ongoing and varied stream of tissue-engineered products using its proprietary core technology. With over 200 different types of cells in the human body, numerous opportunities exist to develop products using tissue engineering techniques developed by the Company. With several strategic partners, the Company is developing products that can positively affect patients' lives.

B.W. Zweifach’s pioneering contributions and dedication to microcirculation spanned a period of over 60 years and led to the birth of Bioengineering as a new integrated academic discipline. Please join us in commemorating a great researcher in microcirculation and an outstanding educator in bioengineering by contributing to the B.W. Zweifach Library.

With B.W. Zweifach’s vision and leadership, Bioengineering at the University of California, San Diego was created and achieved national and international recognition. He served as a rallying point for many engineers and physiologists in the development and application of new techniques to study the microcirculation and related medical problems. He foresaw the tremendous advantage

of integrating engineering and medicine for the solution of important problems and worked for a lifetime to foster interactions between these disciplines.

After a stellar career for more than 31 years with pioneering contributions to cell biology, physiology, and pathophysiology of the microcirculation at New York University and Cornell University, Professor Zweifach came to the University of California, San Diego to help establish a new program in Bioengineering. His work led to the development of fundamental new approaches to study the microcirculation with engineering techniques, which are now used world wide to benefit patients. He was the foremost investigator of small blood vessels in the body and his teachings of the microcirculation have been most influential for well over half of a century. He co-founded and developed the Microciruclatory Society and was an honorary member of many Microciruculatory Societies world-wide. Zweifach left a rich heritage of written records about the mircocirculation and visions about bioengineering education.

The B.W. Zweifach Library will be located in the new Powell-Foct Bioengineering building. It will be a place where Zweifach’s contributions will be documented and on display, where students, faculty, and other scientists will exchange knowledge and information in bioengineering. It will serve as a data bank of knowledge in bioengineering and microcirculation and house a combination of classical research records and the latest internet-based electronic medical library.

Dr. Geert Schmid-Schönbein, Professor of Bioengineering, and his research group, including Hiroshi Mitsuoka and Erik Kistler, have prevented shock and multiple organ failure in experimental animals by blocking powerful pancreatic digestive enzymes in the intestine. This fundamental breakthrough could lead to therapies to prevent and treat ischemic shock following blood loss from traumatic injury or high-risk surgery. The work also provides clues into the cellular mechanisms that lead to shock. Their report titled, "Generation of In Vivo Activating Factors in the Ischemic Intestine by Pancreatic Enzymes," was published in the Proceedings of the National Academy of Sciences on February 15, 2000. The research was funded by the National Heart, Lung, & Blood Institute.

Ischemic shock, which can quickly lead to multiple organ failure and in some cases death, occurs when blood pressure falls after blood loss or deep anesthesia. Early symptoms of shock include cold, clammy skin, mental confusion and inadequate production of urine. These symptoms are induced when activators in the blood stream turn on various cardiovascular cells including leukocytes and endothelial cells. Abnormal interactions between leukocytes and endothelial cells produces inflammation, alters blood flow, and finally cuts off delivery of oxygen to the organs. Vital organs become poorly perfused and starved of oxygen.

The pancreas produces potent enzymes that can digest any tissue. These enzymes are regularly released into the intestines to digest food. Dr. Schmid-Schönbein and his group theorized that when blood pressure falls sharply in the intestine, pancreatic enzymes start to escape from the lumen of the intestine, into the wall of the intestine. These enzymes produce and release dangerous activators into the blood stream, initiating a cascade of events leading to multiple organ failure. Never before have researchers found strong evidence for the source of the cell activators.

To test their theory, they surgically produced shock in rats. Control rats were given no treatment. But the researchers injected a broadly acting pancreatic enzyme inhibitor, 6-amidino-2-naphtyl p-guanidinobenzoate dimethanesulfate, also known as nafamostat mesilate or futhan, into the lumen of the small intestine of the rats prior to inducing shock in the animals. The control rats experienced classic symptoms of shock including a drop in blood pressure, inflammation and multiple organ failure. The treated rats experienced much less pressure reduction, no activation of leukocytes or endothelial cells, no appearance of cell activators in the circulation, no inflammation, and no significant organ injury.

"We have clearly found a key source of the activators that lead to shock. This is a completely new result," said Schmid-Schönbein. "With this knowledge, we can begin to explore effective treatments with the possibility of preventing the death of thousands of people each year." Schmid-Schönbein’s group is testing the procedure with different types of enzyme inhibitors. Dr. Schmid-Schönbein with Dr. David Hoyt, Professor of Surgery, is currently taking the initial steps for human trials. In collaboration with Dr. Tony Hugli of the Scripps Research Institute, Dr. Schmid-Schönbein is working on the identification of the toxic factor produced in shock by pancreatic enzymes.

Anthony Sebald, Associate Dean for Academic Affairs and Professor of ECE, was awarded the Outstanding Educator of the Year award for his continuing contribution to the field of engineering education. The nomination came from the faculty with whom he works at the request of the students. The San Diego Committee for National Engineers Week presented the award at a banquet on February 25.

Andrew McCulloch, Professor of Bioengineering, was awarded a UC Life Sciences Informatics Grant entitled "Information Infrastructure for Tissue-Device Interactions," and an International Program for Animal Alternatives Award entitled "In-Silico and In-Vitro Models of Cardiac Myocyte Hypertrophy."

Shankar Subramaniam, Professor of Bioengineering, was elected a Fellow of the American Institute for Medical and Biological Engineering (AIBME).

Robert Myers, Professor of Medicine, Tamaki Igarashi, Shinichi Kikuchi and Veronica Shubayev won a $10,000 Volvo Award for Basic Science at the International Society for Study of the Lumbar Spine for their paper titled, "Exogenous TNF-alpha mimics nucleus pulposus-induced neuropathology: Molecular, histologic, and behavioral comparisons in rats."

Rick Lieber, Professor of Orthopaedics and Bioengineering, was awarded the "Career Scientist" award through the Department of Veterans Affairs Rehabilitation Engineering Research & Development Service. The purpose of this program is to provide stable research support for V.A. investigators with a history of productivity.

Ajit Varki, Professor of Medicine and Director of the Glycobiology Research and Training Center (GRTC), recently gave invited talks about his work on a unique glycosylation difference between humans and great apes at several fora, including the American Chemical Society, the American Society for Physical Anthropology and the National Human Genome Research Institute (NHGRI) at the NIH. This will also be the topic of Dr.Varki's School of Medicine Faculty Distinguished Lecture on May 23rd. A news item regarding the NHGRI seminar can be found in the April 18 issue of the NIH Record: http://www.nih.gov/news/NIH-Record/archives.htm. The original discovery was made with Elaine Muchmore, Associate Professor of Medicine, who is continuing to work on the potential relevance to cancer.

Michelle Palmisano, graduate student in Bioengineering, will be awarded a 2000 National Leadership Grant by the Order of the Sons of Italy in Washington D.C on May 25, 2000. Ms. Palmissano is one of only twelve recipients of this post graduate scholarship.

Christophe H. Schilling successfully defended his Ph.D. this spring. Dr. Schilling is currently the Chief Technical Officer of Genomatica in San Diego.

Stephen Waldo and Aaron Wang, undergraduate students in the Department of Bioengineering are two of the four UCSD students selected as Beckman Scholars for 2000-2001. Four undergraduate students at the UCSD were selected to receive prestigious awards from the Arnold and Mabel Beckman Foundation, which will allow them to participate in prolonged academic research projects with UCSD faculty members in the sciences. The UCSD students are among 71 undergraduate students from 18 institutions nationwide who were named Beckman Scholars. Stephen Waldo is working with Geert Schmid-Schöenbein, Professor of Bioengineering and Aaron Wang is working with Robert Sah, Associate Professor of Bioengineering.

On April 18, 2000, Dr. Ferid Murad, the 1998 Nobel Laureate in Medicine for his discovery concerning nitric oxide as a signaling molecule in the cardiovascular system, delivered the First Benjamin W. Zweifach Memorial Lecture. Dr. Murad received his M.D. and his Ph.D. in Pharmacology from Western Reserve University, School of Medicine in Cleveland, Ohio. Dr. Murad has held professorships and directorships with many illustrious institutions. He has also been Vice President of Pharmaceutical R&D with Abbott Labs and CEO/President of Molecular Geniatrics Corporation. Currently, Dr. Murad is the Chairman of the Department of Integrative Biology, Pharmacology and Physiology at the University of Texas Medical School at Houston.

Dr. Murad’s lecture was titled "Cell Signaling with Nitric Oxide and Cyclic GMP." Nitric oxide (NO) is a gas molecule that transmits signals in organisms. Signal transmission by a gas that is produced by one cell, penetrates through membranes and regulates the function of another cell, represented an entirely new principle for signaling in biological systems. Dr. Murad and his colleagues, analyzed how nitroglycerin and related vasodilating compounds act and discovered in 1977 that they release nitric oxide, which relaxes smooth muscle cells. He was fascinated by the concept that a gas could regulate important cellular functions and speculated that endogenous factors such as hormones might also act through NO. Active research is being conducted to provide experimental evidence on this idea.

The Zweifach Memorial Lecture was establed in honor of Benjamin W. Zweifach (1910 - 1997), Professor of Bioengineering and a pioneer in the field of human physiology, especially the microcirculation. After a career for more than 31 years at New York University and Cornell University, Professor Zweifach came to UCSD to help establish a new program in Bioengineering in 1966. His work led to the development of fundamental new approaches to study the microcirculation with engineering techniques. He was the foremost investigator of small blood vessels in the body and his teachings of the microcirculation have been most influential for well over half of a century. Please also see Page 4.

UCSD’s Jacobs School Of Engineering Fastest Rising Engineering School In U.S. News & World Report Ranking: UCSD’s Irwin and Joan Jacobs School of Engineering was ranked 15th in the nation by the U.S. News & World Report annual survey of engineering schools. This marks the sixth year running that the Jacobs School has climbed in the rankings, and the School is by far the fastest rising institution among the top 20 universities. In addition, the Jacobs School was 9th among public universities and 2nd in the University of California system. The Department of Bioengineering was ranked 3rd in the nation.

Beckman Scholars award for Undergraduate Research: UCSD was one of 18 schools selected out of 76 applicants to receive a Beckman Scholars award for Undergraduate Research. The UCSD proposal was a joint application from Bioengineering, Biology, and Chemistry.

Bioinformatics, Expanding Research Potential: The UCSD Center for Molecular Genetics in association with the Whitaker Institute of Biomedical Engineering will host this seminar on May 4 and 5, 2000 in the UCSD Price Center. Speakers include Stephen Edwards, Lynda Ellis, Suzanna Lewis, Bernhard Palsson, Ian Paulsen, Alun Thomas, and John Yates. For more information and to register, please contact the Center for Molecular Genetics at (858) 534-0396 or visit the Seminar web site at: (http://www.cmg.ucsd.edu/symposiumreg.html).

Workshop on DNA MicroArray Technology: Dr. Micheal Heller, Chief Technical Officer of Nanogen, Inc. in San Diego and Adjunct Professor of Electrical and Computer Engineering, presented an introductory workshop on DNA Microarray Technology on April 19 and April 20, 2000. The workshop was cosponsored by the Department of Bioengineering, the Whitaker Institute of Biomedical Engineering and the Department of Electrical and Computer Engineering.