Director's Message

The Breakfast with Industry event that took place on November 20, 2001 was a great success. Dr. Billl Craig, Vice President of Research and Product Development at ISTA Pharmaceuticals, was a speaker at this meeting. This regularly held event, sponsored by the Department of Bioengineering and the Whitaker Institute of Biomedical Engineering (WIBE), offers our graduate students, post-doctoral fellows and UCSD faculty a great opportunity to interact with industrial representatives on a one-to-one level.

It is my pleasure to offer an article featuring our long-standing Industrial Affiliates Program member Science Applications International Corporation. Dr. John Penhune, Senior Vice President of Research, is also the Chair of our Industrial Advisory Board.

Dr. Robert Sah, Professor of Bioengineering at UCSD and Member of the Whitaker Institute of Biomedical Engineering, led the study of fabricating joint cartilage which mimics structure and function of natural tissue. The results of this breakthrough research were reported at the last BMES meeting held in October of 2001.

The construction of the new Bioengineering Powell-Focht building is progress on schedule for completion this Fall. We present the status report submitted by the Los Angeles based architects Anshen+Allen.

In the Faculty Honors column of our newsletter we are featuring a founding WIBE member and a member of WIBE Executive Committee Dr. Andrew McCulloch, who has made major contributions to biomedical research and education.

We sincerely congratulate Dr. Fred Gage, Member of the Salk Institute Faculty and an adjunct faculty in UCSD Dept of Neurosciences (School of Medicine), for being elected to the Institute of Medicine and Dr. John West, Professor of Medicine (Physiology) and Bioengineering, for being elected to the American Academy of Arts and Sciences.

Also we congratulate our new graduates for completing their education at UCSD Bioengineering.

I am greatly honored and humbled to be appointed a University Professor. This recognition is made possible by the collaborative work with faculty, students, and staff at UCSD, as well as colleagues in other UC campuses and elsewhere. I would like to take this opportunity to express my sincere gratitude to all of them, to those who nominated me, and to the UC Regents, the Academic Senates, President Atkinson, Chancellor Dynes, Senior Vice Chancellor Chandler, Dean Conn, and Chair Gough for processing and approving this prestigious title. I also thank Denine Hagen of the Jacobs School of Engineering and Tatyana Matusov of WIBE for writing the article about the University Professorship. I will endeavor to meet the high expectations of this appointment.

Dr. Shu Chien, Director

Dr. Shu Chien - University Professor

• Be a successful teacher of exceptional ability. The candidate's ability and desire to teach, simulate, and inspire and to communicate effectively with students should not be limited to majors and specialists in the individual's particular discipline.
• Have interests and accomplishments that extend beyond a particular scientific, scholarly, or creative specialty and must also demonstrate a willingness to serve beyond the home campus.

Those who are fortunate enough to know and work with Dr. Shu Chien, would agree that he definitely meets and exceeds these criteria.

Very few University of California faculty members have achieved this distinction, and to have Prof. Chien hold this appointment while being a faculty member of the Jacobs School and of UCSD brings enormous recognition to him and great pride to the school.

This appointment means that Dr. Shu Chien is now a professor of the University of California as a whole, and while he will maintain his appointment base at San Diego, he will visit and lecture at other campuses to work with students and faculty throughout the system.

Professor Chien was the founding chair of the Department of Bioengineering, the founder and the director of the Whitaker Institute of Biomedial Engineering, a member of the National Academy of Engineering and the Institute of Medicine, and he has received an uncountable number of awards.

WIBE Industrial Affiliate:
Science Applications International Corporation

Founded by Dr. J.R. Beyster and a handful of scientists in 1969, Science Applications International Corporation (SAIC) is ranked #296 on the Fortune 500® listing and is the largest employee-owned research and engineering firm in the nation. SAIC and its subsidiaries have more than 40,000 employees with offices in over 150 cities worldwide. SAIC headquarters are located in San Diego, CA.
SAIC provides a broad range of valuable technical services to its government and commercial customers, much of it in areas related to information technology, information security, systems integration, complex program management, national defense, criminal justice, and counterterrorism.

SAIC also has gained extensive and successful experience in world-class medical research and related activities that may be of particular interest to students and faculty at the Whitaker Institute. For example, the company is working to help develop candidate vaccines for one of the most serious worldwide diseases - malaria. The National Institutes of Health and the National Institute of Allergy and Infectious Diseases awarded SAIC a major contract for malaria vaccine development.

To help fight cancer, AIDS, and related diseases, SAIC conducts leading-edge research for the National Cancer Institute's Frederick Cancer Research and Development Center. SAIC manages and operates the center, which screens compounds for anticancer and antiviral properties, conducts basic and applied research in cancer and AIDS, and operates a high performance computer devoted strictly to biomedical research. In the August 15, 2001 issue of Cancer Research, SAIC's scientists reported that they developed new transplantable mouse tumor cell lines that produce slow-growing renal cell carcinomas. According to the article, these tumors share several traits with the human disease, offering a unique window into the biology of this poorly understood disease.

In addition to helping fight cancer and AIDS, SAIC is helping fight terrorism. SAIC produced a prototype anthrax vaccine for the U.S. Army Medical Research Institute for Infectious Diseases that has been released to undergo Phase I and II testing in people. There is a hope that this may be a vaccine that will prevent disease caused by infection by anthrax spores.

SAIC helps law enforcement solve and prevent crimes, identify contraband, and quickly and securely share critical information. DNA analysis helps investigators solve crimes. SAIC developed the FBI's Combined DNA Index System (CODIS) software, which is an automated DNA information processing and telecommunications system that supports the national, state, and local DNA Index Systems. Just as fingerprints found at a crime scene can be run through the automated fingerprint identification system in search of a suspect or link to another crime scene, DNA profiles from a crime scene can be entered into CODIS, which was developed by SAIC for the FBI. Thus far, CODIS has assisted in more than 1,700 investigations in 29 states. In addition, DNA profiling, including profiles using the CODIS system, helps free the wrongfully convicted.

SAIC encourages employees to maintain the highest standards of quality and ethical conduct, to grow professionally, and to reap the rewards of employee-ownership. SAIC has cutting-edge research and engineering opportunities for new graduates and experienced candidates. SAIC also offers internship and cooperative education experiences for qualified candidates. More information about SAIC is available at www.saic.com.

Bob Sah.
UCSD bioengineers fabricate joint cartilage
which mimics structure and function of natural tissue

University of California, San Diego (UCSD) bioengineers have fabricated cartilage tissue which for the first time mimics the multi-layered structure and cellular functions of natural articular cartilage. The tissue is made entirely from biological materials using a modification of a technique invented at Rush-Presbyterian-St. Luke's Medical Center, Chicago. The researchers hope this tissue could be developed as an implant treatment for the millions of people who suffer from cartilage damage associated with joint injuries, congenital defects, arthritis and age-related degeneration.

Robert Sah, professor of bioengineering at the UCSD Jacobs School of Engineering, led the study, conducted by graduate students Travis Klein and Kelvin Li and staff researcher Barb Schumacher at UCSD, in collaboration with Professors Koichi Masuda and Eugene Thonar of Rush Medical College. Travis Klein described the results at the Biomedical Engineering Society annual meeting on October 6 held in Durham, North Carolina. Robert Sah and his team designed a tissue made up of different types of juvenile

cartilage cells with the notion that the tissue could be implanted into a patient and grow up to conform to the specific geometry of the individual's joint. Next steps in the research will be to conduct animal trials to determine the efficacy of such an implant treatment.

Cartilage is the body's shock absorber, a cushion of durable tissue that protects the knee from a lifetime of walking, bending and running. Though just a few millimeters thick, cartilage is nevertheless quite complex, consisting of a surface, middle and deep region, each with its own distinct composition and structure. In previous research, Sah detailed the mechanical properties of cartilage and found that it is soft at the surface, but 25 times stiffer in the deep regions. Meanwhile, Barbara Schumacher, then at Rush Medical College, found that the cells in the surface region make a key protein, called Superficial Zone Protein, which is a major lubricant of joints.

Using this data, bioengineers at UCSD developed a map for how to organize different types of chondrocytes to mimic the stratified nature of cartilage tissue. They then grew this cell mix together using the ARC (Alginate Recovered Chondrocyte) method developed at Rush, which suspends cells in a gel until the cells begin to form their own matrix or scaffolding. The gel is then removed, leaving an entirely biological tissue.

In laboratory tests, the researchers found that the cells at the surface of their engineered tissue effectively secreted the key molecule, Superficial Zone Protein, needed to lubricate the joint. In addition, the cells at the surface were making tissue that was softer and had a less dense matrix, while the cells in the deeper regions were spaced further apart and had a more densely packed matrix, which made the tissue stiffer.

The researchers believe that the engineered tissue will mature like cartilage does naturally in humans. During fetal development, cartilage cells are densely packed, and the matrix is loosely knit. But as a child grows and the matrix supporting the cartilage gets stronger, cartilage cells spread out. By the time an individual reaches adulthood, the cartilage is mature, the cells become less active, and the tissue is about four fold stiffer than during early development.

The engineered tissue is like immature cartilage, and the researchers believe this will give the implant an advantage because as it continues to mature, it is likely to integrate well and conform to fit with the patient's surrounding cartilage and joint tissue. The research is funded by the National Aeronautics and Space Administration (NASA), the National Science Foundation (NSF), The Rush Arthritis and Orthopedics Institute and the Grainger Foundation.

Bill Craig at Breakfast with Industry

Dr. Bill Craig, Vice President of Research and Product Development at ISTA Pharmaceuticals, spoke at the last Breakfast with Industry on November 20, 2001. This unique professional event, sponsored by the Department of Bioengineering and the Whitaker Institute of Biomedical Engineering (WIBE), offers a distinct opportunity for industrial representatives to

interact on a one-to-one level with graduate students, post-doctoral fellows and UCSD faculty to discuss current and future research goals. The event was co-chaired by Shula Stolkes and Jennifer Marciniak of the Industrial Liaison Committee, UCSD Bioengineering Graduate Students Group.

As ISTA's vice president of research and product development, Bill Craig is responsible for overseeing all pre-clinical research, manufacturing process and methods development, technology transfer to ISTA's API and drug product manufacturers, identification of mechanism of action and quality control for all ISTA drug candidates.

The talk Dr. Craig presented was comprised of two parts. He began by presenting the technology that his company, ISTA Pharmaceuticals, is using to treat serious eye disease. This was directed to the general audience.

This technology platform is based on a very unique and versatile enzyme that is naturally present in the body called hyaluronidase. It is formulated into an injectable product called Vitrase.

ISTA is developing Vitrase to address the treatment of the number one cause of adult blindness in the United States: Diabetic Retinopathy (DR).

Diabetic retinopathy is a progressive disease in which, unfortunately, each step moves a patient closer to potential sight loss.

The most dangerous stage is the proliferative stage (PDR), were a patient is most at risk for sight loss and where they are also at risk of a vitreous hemorrhage or bleeding into the back of the eye.

ISTA is developing Vitrase for two initial indications, first to treat vitreous hemorrhage (VH), followed by a therapy for the early stages of diabetic retinopathy.

The incidence of vitreous hemorrhage is substantial, on a global basis, with well over a million cases annually in the major markets. Today, the treatment options for VH are poor. On the one hand, the initial approach involves waiting for the blood to clear on its own, an outcome that can take months while a patient's vision deteriorates. On the other hand, if that isn't successful, a surgical procedure called a vitrectomy can be employed to remove two thirds of the inner material of the eye. This procedure has significant risks including permanent vision loss and the formation of cataracts in most patients, requiring further surgery.

Treatment with Vitrase can show a measurable reduction in the amount of severe hemorrhage remaining in as little as 8 days. This allows the ophthalmologist to begin to see retinal details. After three weeks, the blood is often largely dissipated and the retinal specialist can see the retinal vessels and view distinct objects such as the optic disk.

The second part of Dr. Craig's talk was directed more to the students. It contained his own experiences and impressions of where the Biotechnology industry stands today and why it is a great time to join its work force.

Dr. Craig focused on the amazing opportunity that the biotechnology industry affords to develop new and interesting products. In addition, because of the tremendous diversity of technologies and products under development, there are almost limitless opportunities for the expression of scientific creativity. Most importantly, it gives those who work in the industry a greater connection to those who benefit most from their successes, the patients.

Economically, although money is tight now for funding new biotechnology ventures and supporting growth in the industry, many companies raised large amounts of capital during the biotech boom of 2000. It is a great time to join a well-funded company with exciting technology. Furthermore, in spite of the financial ups and downs of the stock market and industry financing, the job market in biotech has grown steadily over the past decade.

New Building Construction Update

	Anshen+Allen Los Angeles and its Design Team completed design and documentation phases of the project in August 2000. The Contract Documents were issued for a competitive bidding in the fall of 2000. McCarthy Constructors were selected as the successful bidder and the project began construction at the end of December 2000.
The construction phase is estimated to last 21 months with move-in and final occupancy estimated to take one to two months. The estimated date for completion of construction is September 2002. Progress on the various specific aspects of the construction effort is as follows: Exterior Construction Structure The building structural work is nearing completion with all concrete and steel columns and beams in place. Structural concrete floor decks have been poured and the roof deck will be completed in February. A Topping -off barbecue was held in January to commemorate the substantial completion of the structure.
Exterior Cladding	Precast concrete panels, the primary exterior cladding elements, have been fabricated and are in the process of being installed. The panel installation is complete on two façades and work is continuing on the rest of the exterior. Installation of panels is expected to be complete in February 2002.Curtain wall and metal panel design and fabrication details have been submitted for review and released for fabrication.
Installation of the windows and curtain wall elements is expected to begin in mid-February 2002 and will be completed in April 2002. Installation of stone cladding, which occurs on the Academic Court façade, is expected to begin in April 2002. Roofing work will begin in March/April 2002. With the completion of roofing work, and exterior cladding work the building will be "dried-in" or weather-tight. This will allow many of the more sensitive interior construction activities to begin.
Interior Construction	Mechanical, Electrical and Plumbing Rough-in Building engineering systems are in progress with substantial amounts of the rough-in work completed in the Basement, First and Second floors. The work includes installation of mechanical ductwork, air control valves and control equipment;
electrical panel boards, conduit, j-boxes, switch boxes and receptacle boxes; plumbing piping, valves and stub-outs for piped services and waste lines; fire sprinkler mains and branch lines. The work is continuing on upper floors and is expected to be complete in Spring 2002. Interior Wall Framing Interior wall framing is in progress with most walls and partitions complete on the lower floors of the building. The upper floor wall framing is in progress and will be completed in Spring 2002. Laboratory Equipment and Casework Laboratory casework is currently being fabricated and installation will begin in Spring 2002. Site Work and Underground Utilities Loading Dock Exterior construction of loading dock facilities is expected to begin in mid-February 2002 and continue through March 2002. Underground Utilities Exterior construction of underground utilities will begin in mid-February 2002 and continue through March 2002. Submitted by Anshen+Allen Los Angeles

Announcements

Dr. John West: Dr. John West, Professor of Medicine (Physiology) and Bioengineering, UCSD, has been elected to the American Academy of Arts and Sciences.

Dr. Nigel Woolf, Adjunct Professor of Surgery/Otolaryngology, UCSD: A photomicrograph of some of Dr. Nigel Woolf's work won 2nd place in the "Nikon 2001 International Small World Photomicrography Competition". A picture taken by Dr. Woolf and his technician Max Gratrix, showing some of his research data on cytomegalovirus (CMV) infection in the brain of SCID mice, was included as the picture of the month for February in their 2002 calendar. The Nikon Small World contest calendar is circulated worldwide, in particular to scientists. Please click here, if you want to see the picture. You can also access it at Nikon's educational website- http://www.microscopyu.com/smallworld/gallery/contests/2001/index2001.html

Industrial Advisory Board Meting: The Industrial Advisory Board meeting will be held on February 27, 2002 at 7:30 a.m. in SERF 232. The Industrial Advisory Board is composed of representatives from companies participating in the Industrial Affiliates Program.

Dr. Frank Powell, Professor of Medicine (Physiology) at UCSD and Director, UC White Mountain Research Station, received an NSF grant from the Field Stations and Marine Laboratories Program to modernize the White Mountain Research Station (WMRS) laboratories. WMRS is a UC multicampus research unit with headquarters at UCSD (under Powell's directorship) and four laboratories spanning a 10,000 foot altitude transect in the White Mountains just east of the Sierra Nevada mountains. The grant is being used to provide modern molecular biology capabilities at the low altitude Owens Valley Laboratory and to install a highspeed wireless Internet and telecommunications link between all four laboratories, including the Summit Lab at 14,246 ft above sea level. Also, Rich Wargo, a Science Producer at UCSD TV, was instrumental in obtaining an Informal Science Education supplement from NSF to fund a video production that will highlight the research currently being conducted at WMRS.

Dr. Jeffrey H. Price, Director of the NSF-Whitaker Quantitative Imaging and Confocal Microscopy Resource at the University of California at San Diego, is also CSO of Q3DM Inc., which is a high-throughput microscopy imaging company. In collaboration with Michael Mancini, assistant professor at Baylor College of Medicine, they are developing a specialized, state-of-the-art microscope to visualize cells in research on nuclear architecture.

WIBE Member: Andreew McCulloch

Andrew McCulloch is Professor of Bioengineering at the University of California San Diego, where he joined the faculty in 1987. He is a founding member of the UCSD Whitaker Institute for Biomedical Engineering and serves on the Institute's Executive Committee. He is also a Senior Fellow of the San Diego Supercomputer Center, and a member of the Institute for Molecular Medicine and the Center for Research on Biological Structure. Dr. McCulloch has been Chair of Graduate Studies in Bioengineering since the Department was formed. Dr. McCulloch was educated at the University of Auckland, New Zealand in Engineering Science and Physiology receiving his Ph.D. in 1986. Dr. McCulloch was an NSF Presidential Young Investigator from 1991-96, and has been a Fellow of the American Institute for Medical and Biological Engineering since 1997.

He currently serves on the editorial boards of the American Journal of Physiology: Heart an Circulatory Physiology, Computer Methods in Biomechanics and Biomedical Engineering, and the International Journal of Cardiovascular Medicine and Science, and he has published about 100 articles on experimental and computational cardiac biomechanics and physiology.

With research support from the NIH, NSF, NASA and the UC Life Sciences Informatics program, Dr. McCulloch's Cardiac Mechanics Research Group uses experimental and computational models to investigate the relationships between the cellular and extracellular structure of cardiac muscle and the electrical and mechanical function of the heart during ventricular remodeling and cardiac arrhythmia. Genetically engineered animal models are used to investigate the role of mechanotransduction in ventricular development, hypertrophy and post-myocardial infarction remodeling.

Tissue engineering of the cell microenvironment using microlithography and microfluidics are used to investigate the role of cell-matrix interactions in cardiac mechanical signaling. Computational modeling together with fluorescence optical mapping are used to investigate excitation-contraction coupling and the role of mechanoelectric feedback in action potential propagation. In-silico modeling of signal transduction pathways related to calcium cycling and hypertrophy is a new research area along with the development of new technologies for high-throughput cardiac phenotyping in the fruitfly, Drosophila.

Dr. McCulloch is also co-founder and CEO of Insilicomed, a computational bioengineering startup company that is developing predictive modeling tools for medical device design, diagnostic imaging, surgical procedures and drug discovery based on platform technology under license from UCSD.

Bioengineering Seminar Schedule

Winter Quarter 2002
Room 2111 Warren Lecture Hall
2:30 - 3:30 P.M. Fridays
BE 281 and The Whitaker Institute of Biomedical Engineering

WIBE Faculty Honors

Allen Ryan: Dr. Alan Ryan has been invited to a Nobel Symposium "To Heal Hearing," Stockholm, June 2002. Dr. Ryan also organized an International Conference on the Molecular Biology of Hearing and Deafness in Bethesda, MD in October.

Fred Gage, Member of the Salk Institute Faculty and an adjunct faculty in UCSD Dept of Neurosciences (School of Medicine) has been elected to the Institute of Medicine. The focus of research in this laboratory is on degeneration and regeneration in the adult central nervous system.

Shu Chien received the Distinguished Service Award from the Biomedical Engineering Society at its Annual Fall Meeting.

Researchers' Honors

Jason Haga, Ph.D., a postdoctoral fellow in the Vascular Molecular Bioengineering Lab, received a Certificate of Appreciation at the Fall BMES (Biomedical Engineering Society) meeting for his service as the BMES Webmaster.

Student Honors

Peter Yingxiao Wang is a recipient of the American Physiological Society 2002 Caroline tum Suden/Frances Hellebrandt Professional Opportunity Award to be awarded at the EB2002 meeting in New Orleans from April 20 to 25.

Four bioengineering students were selected for the Achievement Rewards for College Scientists. They are: David Drake, Lisa Eisenman, Joe Lee, Timothy Routh. The ARCS (Achievement Awards for College Scientists) Foundation, Inc. is a national volunteer women's organization founded in 1958. The San Diego Chapter, which supports UCSD, SDSU and The Scripps Research Institute, was started in 1985. This chapter has provided more than $1.5 million for UCSD scholarships and fellowships over the past several years and its members are very pleased when they know that you are aware of all they do for the university. For the 2001-2002 academic year they have contributed $245,000 in financial support for 26 UCSD students. You can find more information on the ARCS Foundation awards at: http://www.arcsfoundation.org/SanDiego/.

Sameer Shah was a finalist for the Journal of Biomechanics award at the recent American Society of Biomechanics held in San Diego in August.
Jennifer Davis won the Outstanding Student Presentation at the recent meeting of the Gait and Clinical Movement Analysis Society in held Sacramento earlier this year.

New Bioengineering Ph.D.'s and Their Current Positions

Yiping Fan - Bioinformatics Scientist, Torrey Mesa Research Institute
Melissa Kurtis - seeking postdoctoral position at Columbia University

Congratulations to all!

University of California, San Diego
Whitaker Institute of Biomedical Engineering
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La Jolla, CA 92093-0427

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