I N T H E N E W S

Director’s Message 2

BLI ‘Relays’ Endometrial PDT 3

Wound Healing Studies 4

Spring 2000

InstitutePursues NewMed School

Collaborations

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Newsbriefs IMAGING THE INNER EAR

Brian J. F. Wong, M.D., AssistantProfessor of Otolaryngology at

the University of California, Irvine’sBeckman Laser Institute, has receiveda $10,000 grant from the NationalOrganization for Hearing ResearchFoundation (Narberth, PA) to sup-port his work on laser-based imagingmodalities for the inner ear.

The award, disbursed under theauspices of the NOHR Foundation’sYear 2000 Research Program, willsupport Dr. Wong’s effort to developan Optical Coherence Tomography(OCT) system with the high-resolu-tion capabilities necessary to distin-guish the miniature anatomicalstructures of the inner ear.

Researchers at the Beckman LaserInstitute have initiated a new

collaborative project with UCI’s De-partment of Neonatal Medicine,pushing to thirteen the total numberof collaborations with departmentsand programs operating within theCollege of Medicine.

The new project, co-directed byFeizal Waffarn, M.D., Associate Pro-fessor in the Department of Neonatal

(newsbriefs continued on p. 8)

Medicine, and Bruce Tromberg,Ph.D., Director of BLI’s Laser Micro-beam and Medical Program, employsBLI’s near-infrared imaging system toimprove endotracheal intubation innewborns with respiratory and otherillnesses.

Conventional imaging methodsfor newborns rely on x-ray, which islimited by cost, time, and radiationexposure. By contrast, optical imag-ing can quickly and precisely locatethe tip of an endotracheal intubationtube through an infant’s chest wall atlow cost and without the use of ion-izing radiation.

Institute Director Michael Berns,Ph.D., views interdepartmental col-laborations as crucial to BLI’s success:“The neonatal collaboration and oth-ers like it prove that medicine cantake big leaps forward on our owncampus when the spirit of coopera-tion prevails.”

The Institute maintains strong col-laborative ties with the Schools ofBiological Sciences, Engineering, andPhysical Sciences. ■

B E C K M A N L A S E R I N S T I T U T E

Ryan Lanning (third from left) and Bruce Tromberg, Ph.D., (thirdfrom right) represented BLI at the annual “UC Day” events (March13-14) in Sacramento. See story on page 7.

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D I R E C T O R’ S M E S S A G E

Beckman Laser Institute and Medical ClinicUniversity of California, Irvine

1002 Health Sciences Road East, Irvine, CA 92612(949) 824-4713 (Administration) (949) 824-7980 (Clinic)

http://www.bli.uci.edu

Board of DirectorsLinda Cahill, Chairman

Arnold O. Beckman, Ph.D., Chairman EmeritusMichael W. Berns, Ph.D., President, CEO, and Vice Chair

George E. Hewitt, Secretary/Treasurer

George L. Argyros Brian R. Demsey Richard A. Nesbit, Ph.D.Patricia Beckman Harry Gray, Ph.D. Robert L. Stoy, Ph.D.

Thomas C. Cesario, M.D. Gavin S. Herbert David S. Tappan, Jr. Richard P. Kratz, M.D.

AdministrationMichael W. Berns, Ph.D., President and CEO

J. Stuart Nelson, M.D., Ph.D., Associate DirectorRuth Bundy, Ph.D., R.N., Clinic Administrative Director

George M. Peavy, D.V.M., Veterinary DirectorRachel Schreiman, C.P.A., M.B.A., Director of Finance

Joyce Zeiler, R.N., Nurse Director

Beckman Laser Institute NewsAlexander Karn

Words of Wisdom: The Writing On My Wallby Michael Berns, Ph.D.Arnold and Mabel Beckman ProfessorPresident and Director

Visitors to my office know that thewhite board in my conference is

adorned by a set of aphorisms,witticisms and rules to live by whichI have collected over the years.

The list grows monthly, and mydaily experiences in life have forcedme to shuffle and re-prioritize someof these “rules,” but the core remainsthe same. I want to share a few ofthese here in the hope that doing sowill reinvigorate the mission whichDr. Beckman and I first undertookin 1982.

❖ Be mindful--integrity is perishable bysuccess. As we become increasinglysuccessful, the temptation to set asideintegrity also increases, even if onlyon a subconscious level.❖ Power corrupts! One really needs tobe careful of this. With power comesresponsibility.❖ The bureaucratic mentality is the onlyconstant in the universe! A favorite lineof mine from Star Trek (the movie). It’samazing how widespread this mentalityis; maybe because it’s easier to bebureaucratic than it is to be creativeand innovative.❖ No “Bucks,” no Buck Rogers. It takesmoney (lots of it) to afford today’s“gadget” technologies. Some days I

wish I had stayed a field biologist sothat I could simply watch the animalsplay and the flowers grow.❖ Don’t be a whiney excuse maker.Accept the consequences of what youdo and don’t play the “blame game”(nobody ever wins). Put the facts onthe table, and let the “chips fall asthey may.”❖ When I grow up, I want to be a littleboy. I am fortunate to have been ableto build my own toys and gadgets ina thirty-year quest for knowledgewith meaningful applications.❖ Failure teaches as much as success.Actually one can learn more fromfailures. Each failure educates us andprovides us new chances for success.❖ You need to communicate clearly toget the result you want. Often we don’tcommunicate effectively; sometimeswe fail to communicate at all. Few ofus are mind-readers so don’t expectsomeone to know what you wantunless it is clearly articulated.❖ Trapped by the trappings of success.We frequently believe ourselves to beas good as other people tell us we are.Worse yet, we may believe ourselvesto be as good as we think we are.❖ Life is a chess game; anticipate themoves of your opponent. Unfortunately,we often need to think in this mannerin order to survive. It never ceases toamaze me how combative academiacan be. It can become very unusual,even downright bizarre, inside the“ivory tower.”❖ We are the architects of our own pain.Both in mind and body we often arethe authors of our own fate. We create

(continued on p. 7)

Pioneering Medicine: BLI ‘Relays’ Endometrial PDT

C L I N I C A L U P D A T E

3

Physicians at the Beckman LaserInstitute and Medical Clinic

made history in January by launch-ing one of the first patient studies onendometrial photodynamic therapy(PDT) for the treatment of dysfunc-tional uterine bleeding.

Researchers and physicians at BLIhave dedicated eleven years to the en-dometrial PDT project, moving thetechnique from the “drawing board”to the clinic in a series of rigorous,step-by-step measures funded by theNIH and “incubated” as part of theInstitute’s longstanding research ontumors. Pending the results of follow-up studies and continued approvalfrom the Food and Drug Administra-tion (FDA), endometrial PDT couldbe ready for second-phase clinical tri-als by the end of 2000.

A Medical Relay Race“Endometrial PDT has been the

culmination of intense institutionalcollaboration,” explains Yona Tadir,M.D., Professor of Obstetrics and Gy-necology and principal investigatorfor the project. “You have to imaginethis undertaking as a relay race withone researcher after another passingalong the baton.”

The project began in 1989 when Dr.Tadir first arrived at BLI as a visitingresearcher. “We started with elemen-tary questions,” says Dr. Tadir. “Forexample, ‘Is the uterus a good targetfor PDT?’” From there, the questionsbecame increasingly complex. Engi-neers, chemists, physicists, and phy-sicians worked together to tackle eachproblem, one after the other. A steady

stream of medical fellowsfrom around the countryand Europe has kept theproject moving forward,and the stewardship of keyUCI personnel, includingDrs. Krist in Keefe andPhilip DiSaia, has helpedto keep the project ontrack. In order to docu-ment their progress, theBLI team has publishedover fifty articles detailingall phases of their work.

The goal, says Dr. Tadir,has remained fixed. “Oursights have always beenset on one thing. We wantedto develop a user-friendly,minimally-invasive officeprocedure which could replace unpre-dictable drug therapies and costly,high-risk surgeries.”

In order to accomplish this, Dr.Tadir and the BLI team had to keepan eye on the competition. Whileother FDA-approved alternatives ex-ist, none, says Dr. Tadir, offers the ad-vantages of PDT.

Unlike the “balloon-type” devicescurrently under development, theproprietary Intrauterine Light Probe(IULP) developed at BLI requires noanesthetic for delivery and eliminatesthe risk of thermal damage whichother devices can produce as they lit-erally “cook” the endometrial lining.

The Promise of PDTPhotodynamic therapy (PDT) uti-

lizes light-sensitive drugs in combi-nation with laser light to selectively

target and ablate (destroy) unhealthytissues. When light of a specifiedwavelength and frequency interactswith these drugs, a chemical reactionbegins which destroys abnormal cellswhere the photosensitizer has con-centrated. Because these photosensi-tive compounds can be delivereddirectly to the diseased or abnormaltissue, PDT offers extraordinary se-lectivity. Healthy tissues are sparedand remain viable while abnormaltissues are fully ablated.

Bruce Tromberg, Ph.D., Director ofBLI’s Laser Microbeam and MedicalProgram, and Michael Berns, Ph.D.,Institute Director, spearheaded manyof the light and drug dosimetry stud-ies which moved endometrial PDTfrom theory to practice. Both werealso instrumental in the development

(continued on p. 7)

Andrew Berger, Ph.D., postdoctoral researcher, withcomputerized light dosimetry model prior toendometrial PDT.

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R E S E A R C H U P D A T E

Wound Healing Studies Help Smooth Our Scars

C uts, scrapes, burns, andincisions need not leave their

mark on us, according to VincentWallace, Ph.D., a postdoctoral re-searcher at the Beckman Laser Insti-tute.

Together with Tatsuro Yomo,M.D., Chung-Ho Sun, Ph.D., andMariah Coleno, a graduate student inChemical and Biochemical Engineer-ing and Material Sciences, Wallace isworking on a wound healing projectwhich combines the high-resolution,deep-tissue imaging capabilities ofthe two-photon microscope with thewell documented principles of pho-todynamic therapy (PDT).

“Can we accelerate wound heal-ing? Can we reduce scarring? I’mconfident we can,” says Wallace, whojoined the research staff at BLI in 1997after completing his doctoral work atthe University of London’s Instituteof Cancer Research. “The trick will beto determine exactly what biologicaland chemical parameters affect theprocess. We’re looking at the healingprocess to see exactly how this works.”

A Biological OrchestraThe biology of wound healing is

extraordinarily complex. Specializedcells known as monocytes and mac-rophages migrate through the extra-cellular matrix of damaged tissues,acting as tiny “conductors” whichorchestrate the healing process. Thesecells release cytokines (i.e., growthfactors) which are responsible forstimulating tissue contraction andregeneration. Too few cytokines re-sult in poor or prolonged wound

healing; too many cytokines produceinflammation and swelling.

Wallace uses two-photon micros-copy to monitor collagen synthesisand regeneration in damaged tissues.Preliminary studies indicate that pho-todynamic therapy (PDT), a wellknown cancer treatment which em-ploys laser light in combination withphotosensitive drugs, inhibits the re-lease of growth factors in damagedtissue and consequently slows downthe process of tissue contraction. Thesignificance of these results is two-fold, according to Wallace.

“We’re learning, first of all, that wecan slow down the natural healingprocess. This is significant because itgives us increased control over scarformation. At the same time, it ap-pears that PDT allows us to reduceinflammation which typically retardsthe healing process.”

Practical ApplicationsWallace’s research will likely sup-

port a wide range of potential clini-cal applications. In the case of electivesurgeries, low-dose PDT might beused to minimize the effects of scar-ring. In the event of trauma or emer-gency surgery, a slightly higher doseof PDT might be administered to con-trol inflammation and promote morerapid healing.

“We’re really talking about tailor-ing the healing process to address theneeds of individual patients,” saysWallace. “The body’s own chemistrygives us that flexibility.”

Current studies, funded by the De-partment of Defense, Office of NavalResearch (DOD-ONR) monitor heal-ing in artificial tissue cultures knownas RAFT models. The next phase ofWallace’s research will target livingtissue samples. ■

Laser-assisted wound healing may be around the corner. (L-R) Tatsuro Yomo, M.D.,Vincent Wallace, Ph.D., Chung-Ho Sun, Ph.D., and Mariah Coleno, M.S., pose infront of the two-photon imaging microscope.

5

S T A F F P R O F I L E

Institute Contributors and PartnersGOV’T AGENCIES AND FOUNDATIONSArnold and Mabel Beckman Fndn.

The David and Lucile Packard Fndn.Department of Commerce

Department of Defense (ONR)Department of Energy

The George E. Hewitt Fndn. forMedical Research

Hester Family FoundationHoag Foundation

National Institutes of HealthWhitaker Foundation

SUPPORTERSDr. and Mrs. Jay Applebaum

The Argyros FoundationDr. Arnold O. Beckman

Patricia BeckmanDr. and Mrs. Michael W. BernsDr. and Mrs. Matthew Brenner

Mr. and Mrs. Nathaniel BrennerMarilyn Burton

Cheng-Jen Chang, M.D.The John Chao Family

Dr. and Mrs. W. Andrew CiesDr. Howard and Rita ConnMr. and Mrs. Duke Cooper

Mr. and Mrs. Brian DemseyDr. and Mrs. Norman Frankel

Mrs. Frederick GarryMr. and Mrs. Walter Gerken

Marilyn Hester GianuliasDr. and Mrs. Frederick Grazer

Mr. and Mrs. Gavin HerbertNora Hester

Mr. George HewittRobert L. Jones, M.D.

Dr. and Mrs. Richard KasperMr. and Mrs. Robert KleistDr. and Mrs. Richard KratzWallace Landholm, M.D.

Richard McCleary and Ileen FrankelFrank and Linda Meyskens

Mrs. Warren S. Myers & FamilyTricia and Al Nichols

Richard and Hinda Rosenthal FoundationMrs. Audrey M. Schneiderman

Mr. and Mrs. Robert W. SchollerMr. and Mrs. John Stahr

Mr. and Mrs. Robert StermanThomas T. and Elizabeth C. Tierney

D.E.L.T.A. RescueOrange Coast Rhodesian Ridgeback Club

Premier Laser Systems, Inc.

Shoreline Dog Fanciers AssociationS. California Veterinary Medical Assoc.,

Orange County ChapterS. California Veterinary Medical Assoc.,Saddleback-Capistrano Valley Chapter

INCUBATOR CORPORATE PARTNERSCandela CorporationNewport CorporationPhotoSense L.L.C.

CORPORATE AFFILIATESAllergan, Inc.

Beckman Coulter, Inc.Coherent, Inc.

ESC Sharplan Lasers, Inc.SmithKline Beecham

INDUSTRIAL ASSOCIATESBio-Safe America

CandelaCarl Zeiss, Inc.

DUSA Pharmaceuticals, Inc.Hewlett Packard

Medical Optics, Inc.Olympus

Physical Optics Corporation

Sheryl Cherrison: Administrative Specialist

Sheryl Cherrison won’t back downfrom a challenge. Whether she’s

on the tennis court volleying her wayto victory or in the office wrestlingwith yet another administrativedeadline, Sheryl has no troublestretching herself to the limit.

“In my mind, that’s the uniqueaspect of working in a university set-ting,” Sheryl says. “You’re alwaysconfronted with opportunities forlearning and personal growth.”

A native of Southern California,Sheryl arrived at BLI in 1996 after thir-teen years in Redding, California,where she served in administrationfor the public schools. Along withhusband, Larry, a respiratory thera-

pist at UCI‘s Medical Center andpart-time pastor at the Mariners’Church in Irvine, Sheryl has lived anddeveloped her career in Washington,Texas, and Montana.

Coming home to the Southlandhas given Sheryl a chance to enjoyfamily and to find her place in the BLIfamily as well. “For me, it’s impor-tant to be proud of the place whereyou work. I hold my colleagues inhigh regard, and I feel confident re-ferring a friend.”

Sheryl and Larry have four chil-dren: Eric, 30; Cristian, 28; Charity, 22;and Shannan, 14. In addition to herpassion for tennis, Sheryl enjoys avariety of church activities, walking

on the beach, reading, and spendingtime with her kitten, Tucker, and hertwo “grand-dogs,” Madison andCreeper. ■

Sheryl Cherrison, Admin. Specialist.

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V E T E R I N A R Y U P D A T E

AVON PLEDGES $2.2M FOR BREAST CANCER RESEARCHInstitute Receives New Diagnostics Funding Component

T he University of California,Irvine and the Beckman Laser

Institute have received major fundingfrom the Avon Breast Cancer Crusadeto expand research on breast cancerdiagnosis and treatment.

UCI will receive $2.2 million, aportion of the $14 million gift Avonis awarding to five breast cancer re-search facilities around the nation. Apercentage of the UCI gift, adminis-tered by the Medical Center’s ChaoFamily Comprehensive Cancer Cen-ter, will go to support continuingwork on a laser-based diagnostic de-vice for the detect ion of early,pre-cancerous growths in the breast.

The laser diagnostic device, devel-oped by Bruce Tromberg, Ph.D.,Director of BLI’s Laser Microbeamand Medical Program, and John But-ler, M.D., Professor of SurgicalOncology, measures the absorptionand scattering of laser light as itpropagates through breast tissue.

“We are proud to partner with UCIrvine and other beneficiaries to seekthe possible causes, prevention, treat-ment, and cure of breast cancer,” saidPatricia Sterling, Senior Manager,Avon Breast Cancer Crusade.

“It certainly provides us a boostwhen corporations like Avon take aleadership role,” adds Tromberg. ■

Quincy’s Pride: Humans Helping Animals

Quincy’s options were few whenthe seven year-old mixed breed

terrier arrived at the Beckman LaserInstitute for treatment. A deep tissuelesion, known as a cutaneous angi-omatosis, had intruded the right sideof Quincy’s face, making normal ac-tivities a challenge.

“Routine surgery would have re-quired removal of all of the affectedskin on the right side of the face. Thatwasn’t an option,” says Dr. GeorgePeavy, D.V.M., Director of the Institute’sVeterinary Outreach Program.

Instead, Peavy teamed with StuartNelson, M.D., Associate Professor ofSurgery, to perform a laser procedurewhich Nelson has honed for the treat-ment of port wine stain (PWS) lesionsin humans.

Peavy and Nelson usedthe Institute’s Nd:YAG laserduring two treatment ses-sions to “photocoagulate”Quincy’s vascular malforma-tion. “The absorption by he-moglobin circulating in thelesion results in thermal ne-crosis of the affected tissue,”explains Dr. Peavy. Follow-ing treatment, the lesionscabs and sloughs, leavingbehind healthy, blanchedskin.

“Quincy is the real winnerhere,” notes Dr. Peavy. “Wetook an established technol-ogy from human medicineand applied it to an animalthat had no other options.” ■

Quincy poses for the camera before (inset) andafter laser treatment for a vascular malformationaffecting the skin over the right side of her face.

It’s Your Health✓ 1 in 8 women in the

U.S. will be diagnosedwith breast cancer.

✓ Breast cancer is themost common form ofcancer among women.

✓ The incidence ofbreast cancer hasbeen rising over thepast two decades.

✓ Early detectionimproves chances forsurvival.

Source: National Cancer Institute

7

(cont’d from page 2)

Words of Wisdomof Tadir ’s IULP, the miniature (2.5mm) fiber-optics-based device whichdelivers light into the uterine cavity.

“We’ve drawn on a huge pool oftalent,” Tromberg says. “In someways, this is the mother of all inter-disciplinary projects at BLI. This iswhat happens when basic science andgood pre-clinical models meet for-ward-thinking engineering andmedical expertise.”

Oncologists have used PDT totreat tumors for more than fifteenyears. Researchers at BLI are amongthe first to successfully apply thetechnique to gynecological medicine.

“More than 100,000 hysterecto-mies are performed each year to treatdysfunctional uterine bleeding,”states Dr. Tadir. “These are major pro-cedures with long recovery periodsand the possibility of severe compli-cations. I am confident that a signifi-cant number of these surgeries can beavoided with the application of this

new technique.”The BLI team is currently working

to recruit patients for additional test-ing. Assuming these studies gosmoothly, Dr. Tadir sees a range ofapplications for endometrial PDT. Se-lective endometrial ablation prior tohormone replacement therapy (com-monly prescribed to improve qualityof life in post-menopausal women)might eliminate the heavy bleedingwhich frequently occurs as a side ef-fect. Endometrial PDT could also playa role in the treatment of pre-cancer-ous lesions affecting the uterus.

Institute Director Michael Berns,Ph.D., gives the project high marksfor innovation and collaboration.“When Dr. Beckman and I talkedabout the meaning of interdiscipli-nary science back in 1982, this is thekind of project we both had in mind.Our federal core support depends onour ability to take ideas like this frombasic science to clinical trials.” ■

(cont’d from p. 3)

ENDOMETRIAL PDT: ‘RELAY’ SCIENCE

STUDENT RESEARCHER WINS UC ACCOLADESUndergraduate Selected For “UC Day” Panel

situations and strive for achievementsthat consume our energies andeventually can subject us to pain anddiscontent. It is too easy, I think, toblame others for the unrealisticdemands we often place on ourselves.When life starts to hurt, it is importantthat we take time for “soul-searching”and introspection.❖ Pain is a teacher with a profoundmessage. Each instance of pain is alesson in life, a hint that something iswrong. We need to listen to thesemessages very carefully so as to avoidor ameliorate future pain. Listen towhat hurts and adjust accordingly.❖ Don’t take yourself too seriously(AOB’s Rule # 7). This is one of Dr.Arnold Beckman’s “rules of life.”Sometimes we get so caught up in ourown self-importance or the importanceof the task at hand that we lose sightof the real ly important th ings .Remember to make time for the littlethings. Stop to “smell the flowers.”Above all, make sure you spend timewith your loved ones.❖ Don’t embarrass yourself or others(Rule #2). This is another of Dr.Beckman’s profound messages. Sooften we do stupid and/or selfishthings that not only tarnish our ownimage but also damage the reputationsof friends, family, and mentors--thepeople who have placed their faithand trust in us.❖ Put yourself in the other person’s shoesbefore reacting. We often react withoutthinking or considering how ourresponses will affect others. Take agood look before you leap. Askyourself: what would you do if youwere in the other person’s shoes? Itmay help you understand peoplebetter and, as a result, cause you toreact less often (or at least moreconstructively). ■

F ourth year student, RyanLanning, a Biology/Chemistry

double-major at UCI, traveled to Sac-ramento in March to present his workto University of California PresidentRichard Atkinson and a group ofCalifornia State legislators.

Selected as one of nineteen under-graduate stand-outs from eight UCcampuses, Lanning participated on apanel of young researchers who wereinvited to the state capital for the an-nual “UC Day” events.

Lanning, a native of Escondido,California, presented the results of hisresearch on breast cancer diagnostics,a project he has been working on for

the past two years under the super-vision of Bruce Tromberg, Ph.D., Di-rector of BLI’s Laser Microbeamand Medical Program (LAMMP). Theannual UC Day events highlight theeducational and research advancesthat have contributed to the state’seconomy and quality of life.

Research opportunities, once arare thing for undergraduates, are be-coming an increasingly importantpart of the university experience.“Research has been great,” Lanningsays. “I’d rather be in the lab thanburied in class. [The lab] is where[students] see how everything fitstogether.” ■

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Johannes de Boer, Ph.D., and Chris Saxer, Ph.D., take a break from their experiments.De Boer is working with researchers at the University of Texas, Austin to construct aretinal imaging device for the early detection of glaucoma. For more on imagingmodalities for the eye, see “Keeping an Eye on Vision” at left.

(cont’d from page 1)KEEPING AN EYE ON VISION

Johannes de Boer, Ph.D., AssistantAdjunct Professor of Surgery, has re-ceived new project funding from theNational Eye Institute at the NationalInstitutes of Health (NEI-NIH) tosupport continuing, multi-institu-tional research on diagnostic imag-ing of the human eye using polarizationsensitive tomography.

The four-year project, directed byH. Grady Rylander, M.D. (Universityof Texas, Center for Biological andMedical Engineering), provides $1.7million for the design and construc-tion of new diagnostic instrumenta-tion for retinal imaging as well asfunds for pre-clinical and clinical tri-als for the new imaging device. Join-ing the BLI-Texas team in thiscollaborative endeavor are a core

group of researchers at the Swiss In-stitute of Applied Optics (IAO).

“If fully successful,” one memberof the NIH review committee com-ments, “[the proposed research]

would provide a significant newmethodology for bioengineering,and it would have a large impact onhuman health.” The project will runthrough January 2003. ■