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  CAncer REsearch
3rd Quarter, 2013
 In This Issue 


  Cancer Center Member Spotlight
  Clinical Trial Spotlight
  Congratulations!
  Contact Us
  Did You Know?
  Director's Corner
  Don't Forget
  DOT Highlight
  Feature Story
  Funding Opportunities
  Help Us Help You
  In the News
  Latest Grant Awards
  New Faces
  Program Highlight
  Recent Publications
  Shared Resource Highlight
  Social Networking Tools
  You are Invited...

Research Programs
Our research efforts are organized in four research programs, which serve to foster interactions and collaborations within specific themes. Cancer center members are usually affiliated with one program but work with collaborators from different programs in multidisciplinary groups.

The Chao Family Comprehensive Cancer Center's four research programs are:

Cancer Prevention & Prognosis (CPP)
Chemical Structural Biology (CSB)
Onco-Imaging & Biotechnology (OIB)
Systems, Pathways & Targets (SPT)

In addition, the cancer center has Associate Members (AS).

 Countdown to the Progress Report

Calendar

days until the cancer center's progress report is due, Nov. 27, 2013.
 Did You Know?  


?

Dr. Rita Mehta’s trial (SWOG S0226) was highlighted in the National Cancer Institute’s annual plan and budget proposal for fiscal year 2013, The National Cancer Program: Managing the Nation’s Research Portfolio - 2013. This study showed that combining two anti-estrogen drugs, anastrozole and fulvestrant, extended the median survival time of women with hormone receptor-positive metastatic breast cancer by more than six months, compared with those who underwent standard treatment with anastrozole alone.

 You are Invited...  

Invitation

Welcome reception in honor of Dr. Richard Van Etten
Oct. 28
5:30 p.m. Reception
6 p.m. Remarks
UC Irvine Medical Center, Chao Family Comprehensive Cancer Center (Building 23)

Colon DOT Meeting
Oct. 29, 5 p.m.
UC Irvine Medical Center
Building 3, Room 101

Prostate DOT Meeting
Oct. 30, 3 p.m.
UC Irvine Medical Center
Douglas Hospital, Room 4843

Annual Scientific Retreat
Nov. 15-16
Hyatt Regency Suites
Palm Springs, CA


Skin DOT Meeting
Nov. 25, 1 p.m.
BLI, UC Irvine campus

Colon DOT Meeting
Nov. 26, 5 p.m.
UC Irvine Medical Center
Building 22A, Room 2114

Prostate DOT Meeting
Nov. 27,
3 p.m.
UC Irvine Medical Center
Douglas Hospital, Room 4843

 Funding Opportunities  


$

Internal Funding Opportunities

Please contact:
Jacqueline Tidball
Associate Director, CCSG Administration
tidball@uci.edu

External Funding Opportunities


The cancer center’s extramural awards analyst provides services that include researching federal and private funding opportunities and discovering project-specific funding sources, in addition to timely editorial and proposal writing support.

Please contact:
Alisz Demecs
Extramural Awards Analyst
ademecs@uci.edu

 Latest Grant Awards  


Awards

Awards listed are cancer-related, more than $500,000 (direct) and are for the total award period.

Bruce Blumberg (SPT)
“Transgenerational inheritance of prenatal obesogen exposure”
NIH-NIEHS
Direct Award: $2,803,165

Jennifer Prescher (OIB)
“Expanding the Bioluminescent Toolbox for Multicellular Imaging for Tumor Heterogeneity”
NIH-NIGMS
Direct Award: $950,000

Christopher Hughes (OIB)
“(PQD5) Development of in Vitro Vascularized Microtumors for Drug Screening”
NIH-NCI
Direct Award: $830,000

Gregory Weiss (CSB)
“DNA Polymerase with Single-Molecule Resolution: Activity, Inhibition, and Drug Resistance”
NIH-CSR
Direct Award: $760,000

 Recent Publications  

Publications

Chen JH (OIB), Pan WF, Kao J, Lu JL, Chen LK, Kuo CC, Chang CK, Chen WP, McLaren CE (CPP), Bahri SS, Mehta RS (OIB), Su MY (OIB): Effect of taxane-based neoadjuvant chemotherapy on fibroglandular tissue volume and percent breast density in the contralateral normal breast evaluated by 3T MR. NMR Biomed 2013 Aug IF(N/A) PM23940080.

Lee JH, Le VH, Steinhoff A, Hoang BH (SPT): Vascular tumor in metal-on-polyethylene THA requiring hemipelvectomy. Orthopedics 2013 Jul 36(7): e974-7 IF(N/A) PM23823059.

Komarova NL (SPT): Spatial stochastic models of cancer: Fitness, migration, invasion. Math Biosci Eng 2013 Aug 10(3): 761-75 IF(N/A) PM23906148.

Hwang-Verslues WW, Chang PH, Jeng YM, Kuo WH, Chiang PH, Chang YC, Hsieh TH, Su FY, Lin LC, Abbondant, Lee EY (SPT), Lee W (CSB): Loss of corepressor PER2 under hypoxia up-regulates OCT1-mediated EMT gene expression and enhances tumor malignancy. Proc Natl Acad Sci U S A 2013 Jul 110(30): 12331-6. IF(N/A) PMC3725072, PM23836662.

Tian X, Zhang S, Liu HM, Zhang YB, Blair CA, Mercola D (CPP), Sassone-Corsi P (SPT), Zi X (CPP): Histone lysine-specific methyltransferases and demethylases in carcinogenesis: new targets for cancer therapy and prevention. Curr Cancer Drug Targets 2013 Jul 13(5): 558-79 IF(N/A) PMC3703250, PM23713993.

Liu FW, Randall LM (SPT), Tewari KS (CPP), Bristow RE (CPP): Racial disparities and patterns of ovarian cancer surgical care in California. Gynecol. Oncol. 2013 Sep IF(N/A) PM24016407.

Tay GC, Gesinski MR, Rychnovsky SD (CSB): Formation of highly substituted tetrahydropyranones: application to the total synthesis of cyanolide a. Org. Lett. 2013 Aug 15(17): 4536-9 IF(N/A) PM23962271.

Rodriguez-Brenes IA, Wodarz DF (SPT), Komarova NL (SPT): Minimizing the risk of cancer: tissue architecture and cellular replication limits. J R Soc Interface 2013 Jul 10(86): 20130410 IF(N/A) PMC3730689, PM23825115
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 Social Networking Tools  

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 Help Us Help You


Employee Bulletin
If you have a new grant, were recently published, won an award, or have other newsworthy items, please let us know so we can publicize them in the newsletter and other media outlets. You deserve the accolades!

Send items to: tidball@uci.edu

 Contact Us  

Jennifer Ivask
Community Engagement Manager
jivask@uci.edu


Jacqueline Tidball
Associate Director, CCSG Administration
tidball@uci.edu

 Useful Websites 


UC Irvine Links:
Chao Family Comprehensive Cancer Center
  Research Programs
   Shared Resources
   Disease Oriented Teams
   Clinical Trials

Cancer Research Institute
Center for Functional Onco-Imaging (CFOI)
Center for Complex Biological Systems (CCBS)
Beckman Laser Institute
Network for Translational Research Optical Imaging (NTROI)
Genetic Epidemiology Research Institute (GERI)
Sue & Bill Gross Stem Cell Research Center
UC Irvine Health
UC Irvine School of Medicine
UC Irvine


Organizational Links:
National Cancer Institute (NCI)

Cooperative Links:
Alliance for Clinical Trials in Oncology
Children's Oncology Group
ECOG-ACRIN Cancer Research Group
Gynecologic Oncology Group
National Surgical Adjuvant Breast and Bowel Project
Radiation Therapy Oncology Group
SWOG


 Don't Forget  

Employee Bulletin
Federal funding that maintains support for cancer center cores (keeping prices low) depends critically on papers published that use our center facilities. As NIH transitions to digital, it becomes critically important that you list the support of the Cancer Center Support Grant (CCSG) in all appropriate publications. Verification of acknowledgment of support will come from electronically scanned publications and cannot be altered after publication. It is essential that you cite the CCSG if your publication is cancer-related and supported by the center, such as: "Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA062203. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”



 Director's Corner

Sheldon Greenfield, MD
Interim Director, Chao Family Comprehensive Cancer Center

Greenfield I'm honored to have had the opportunity to guide the Chao Family Comprehensive Cancer Center through a time of change and transition. I have been extremely fortunate to have served alongside a team of committed and talented clinicians, scientists, nurses and staff who are dedicated to working together to provide the highest quality patient care and to pursue cutting-edge cancer research that will have the greatest impact on preventing cancer and treating patients with the disease.

As you know, Dr. Richard Van Etten began his new role as the cancer center’s new director on Oct. 1. We are very excited about the level of expertise Van Etten brings to the Chao Family Comprehensive Cancer Center. He will continue the cancer center’s tradition of excellence in cancer prevention, treatment and research and provide additional skills to advance our cancer center.

Please join me in welcoming Dr. Van Etten to his new appointment.

Greenfield Signature

Sheldon Greenfield, MD
Interim Director
Chao Family Comprehensive Cancer Center


 Feature Story  
Welcome to Dr. Richard Van Etten, new director of the Chao Family Comprehensive Cancer Center

VanEttenDr. Richard Van Etten has been appointed director of the Chao Family Comprehensive Cancer Center. Upon his arrival on Oct. 1, 2013, Van Etten assumed the duties that have been ably handled by interim director, Dr. Sheldon Greenfield. The cancer center is grateful for Greenfield’s leadership and service during this time. The cancer center director search committee, under the leadership of Dr. Ranjan Gupta, was involved in recruiting, screening and interviewing candidates for the cancer center’s top position.

Van Etten’s research focus is the development and preclinical testing of new treatments for hematologic malignancies, including immune therapies and molecularly targeted drugs. His laboratory is focused on the transformation and leukemogenesis by dysregulated tyrosine kinases, and he is recognized for his research in chronic myeloid leukemia and other myeloproliferative neoplasms. His clinical specialties include hematopoietic stem cell transplantation, CML and pH-negative MPNs, and acute leukemia. During his tenure at Tufts Medical Center, he served as director of the Tufts Cancer Center and directed a highly successful research laboratory, funded by the National Institutes of Health and the Leukemia & Lymphoma Society, at Tufts’ Molecular Oncology Research Institute. He holds BS degrees in biology and mathematics from MIT and received both his medical degree and PhD in biophysics from Stanford University School of Medicine. He completed postgraduate training in internal medicine and hematology at Harvard’s Brigham and Women's Hospital.

Van Etten will continue to build on the cancer center's reputation, which was established by its founding director, Dr. Frank Meyskens, vice dean for UC Irvine Health School of Medicine and the Daniel G. Aldrich Jr. Endowed Chair. Under Meysken's leadership, the cancer center received designation as a comprehensive cancer center by the National Cancer Institute (NCI). Today, it is one of only 41 such acclaimed centers in the U.S.

As the cancer center's new director, Van Etten will serve as the principal investigator of the NCI Cancer Center Support Grant and will integrate the cancer center's research and clinical endeavors. He will seek to partner with UC Irvine faculty to bridge basic, clinical and translational cancer research throughout the UC Irvine research community.

UC Irvine Health is truly fortunate to have Dr. Van Etten join our organization. His leadership, integrity, diligence and vision will ensure that the national reputation of excellence for the Chao Family Comprehensive Cancer Center will continue into a new phase of growth.




 In the News  

UC Irvine is the first hospital in the nation to purchase and use the MarginProbe® System
Designed to cut down on repeat surgeries for breast cancer

Police
Alice Police, MD

In the Media: The Orange County Register reported that UC Irvine is the first hospital in the nation to purchase and use the MarginProbe® after the FDA gave its approval Jan. 2. Dr. Alice Police (AS) uses this innovative device during breast cancer surgery. This new procedure is currently performed only at UC Irvine for the treatment of women diagnosed with breast cancer.

LearnMore


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Radiation timing matters
Plikus
Maksim Plikus, PhD

In the Media: The Orange County Register highlighted a collaborative study by UC Irvine, University of Southern California and Salk Institute for Biological Sciences that found that hair loss occuring from radiation treatment is linked to the time of day the treatment is administered. Maksim Plikus, PhD (SPT), the lead researcher from UC Irvine who specializes in hair growth biology, said the findings could play a significant role in cancer treatment protocol.


LearnMore


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Radiation therapy damages neurons
Cranial irradiation, a common brain cancer treatment, disrupts neural morphology in mice in ways that resemble damage caused by neurodegenerative conditions.


Charles Limoli, PhD

Cranial radiation therapy, or radiation targeted to the brain, has been an effective means of decreasing the size of brain tumors. However, the treatment is known to cause neurological dysfunction later in life, though the exact mechanisms underlying the damage have not been clear. Charles Limoli's (SPT) research published July 15 in the Proceedings of the National Academy of Sciences, demonstrates that the life-saving therapy compromises the structure of neurons in mice.

LearnMore


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Past colon cancer tied to future cancer risks
People who have had colon cancer are 15 percent more likely to be diagnosed with another cancer than those with no history of the disease, a new study suggests

Jason Zell, DO (CPP)
Using data from cancer registries from nine states, researchers found small intestine, lung, kidney, stomach, bladder and endometrial cancers were all more common among people with a history of colon cancer.






LearnMore



 Clinical Trial Spotlight  
UCI-10-13: “Pilot study comparing the pharmacokinetics of sorafenib in the Asian-American population vs. non-Asian population in the treatment of hepatocellular carcinoma"

Principal Investigator: David K. Imagawa, MD, PhD (SPT)

Imagawa Sorafenib is the first and only agent to receive FDA approval for the treatment of surgically unresectable hepatocellular carcinoma, which has a high incidence among the Asian-American population. The FDA approval of sorafenib was based on a recent large, multicenter, prospective, Phase 3 study (SHARP III Trial)1 which showed a significant prolongation of median survival of nearly three months with sorafenib.

The recommended dose of sorafenib used was 400mg orally twice daily, with the mean dose used in the SHARP III trial being 700mg daily and the patient population predominantly from Europe, North America and South America. However, a recent retrospective quality analysis and clinical observation by the Department of Surgery at UC Irvine showed that the maximum dose of sorafenib tolerated by the Asian population was significantly lower, with most unable to tolerate the recommended dose of 400mg twice daily. A significant difference in body surface area (BSA) was also noted. This was part of our department’s own clinical observation and follow-up of patients taking sorafenib who are under our care.

The rationale for this study is that a potential difference in the pharmacokinetics of sorafenib metabolism between the Asian-American population and non-Asian population exists and has not been prospectively studied. Thus we are proposing a pilot, prospective study comparing the pharmacokinetics of sorafenib in a group of Asian-American patients already on sorafenib vs. a group of Non-Asian patients already on sorafenib.

1 Spinzi G., Paggi S., Copur M. S., Palmer D. H., Llovet J. M., Bruix J., Roberts L. R., Sorafenib in Advanced Hepatocellular Carcinoma. N Engl J Med 2008; 359:2497‐2499 (PMID:19052134)

Learn More

 Cancer Center Member Spotlight  

The Cancer Center Member Spotlight recognizes the diverse contributions made by the Chao Family Comprehensive Cancer Center members in research, education and patient care. The profiled members reflect the great work being done here and the dedication and values we possess. To suggest someone to be profiled, please contact Jacquie Tidball at tidball@uci.edu

Marian L. Waterman, PhD (SPT)
Professor, Microbiology & Molecular Genetics, School of Medicine

As co-leader of the Systems, Pathways and Targets (SPT) program, Marian Waterman, PhD, works to foster both cancer-related intra- and inter-programmatic collaborations among cancer center members. She is associate director for the Cancer Research Institute, where it is her responsibility to facilitate and coordinate basic research and training at UC Irvine. Additionally, Waterman is professor and vice chair of the Department of Microbiology & Molecular Genetics, School of Medicine, where she provides leadership and direction.

As a member of the cancer center leadership, Waterman works to address key challenges posed by the cancer center director or other members of the senior leadership council and the program leaders committee, as well as issues raised by ad hoc consultants and members of the External Scientific Advisory Board. She directs the program leader committee that evaluates applications for cancer center membership and she leads efforts to develop campus activities of research, professional symposia, and scientific collaborations. Collaboration among the cancer center membership is her personal goal and a highly valued aspect of her own science. Waterman collaborates with numerous groups at UC Irvine, including cancer center members and members of the Sue and Bill Gross Stem Cell Center and the Center for Complex Biological Systems. Specifically, she has collaborated with Lawrence Marsh, PhD (SPT); Bert Semler, PhD (SPT); Klemens Hertel, PhD (SPT); Peter Donovan, PhD (SPT); Rob Edwards, MD, PhD (SPT); Christopher Hughes, PhD (OIB); Lan Huang, PhD (SPT); Steve George, MD, PhD (OIB); Enrico Gratton, PhD (SPT); John Lowengrub, PhD (SPT); Chad Garner, PhD (CPP); Pierre Baldi, PhD (SPT) and Tom Schilling, PhD (SPT). Her work also involves extensive use of cancer center-supported Cores. As co-leader of the SPT Program with John Lowengrub, PhD, she organizes retreats, seminars and facility interactions among SPT members.

Waterman studies Wnt signaling and cancer, with a specific focus on Wnt regulation of target genes by the LEF/TCF transcription factor family. As a post-doctoral fellow, she purified and cloned one of the first members of the LEF/TCF family from lymphocytes. LEF-1 was later discovered to be a mediator of Wnt signaling, with overactive Wnt signaling tightly linked to cancer in many different tissues. In this context, LEF/TCFs are transcription factors that translate overactive Wnt signaling into oncogenic signals. Her research program focuses on this aspect of LEF/TCFs, their activity within the context of Wnt signaling and cancer, and also the regulation of the genes that encode LEF/TCFs. From this focus, her group discovered that LEF/TCF expression and activities are distorted in cancer as compared to normal cells. Her group has also discovered alternative forms of LEF/TCFs produced either from internal promoter or alternative splicing patterns. A new DNA binding domain, a Groucho binding motif, importing binding motif, phosphorylation sites, and selective target genes are additional discoveries. Most recently, her group discovered that Wnt signals from the extracellular environment can influence genetically activated Wnt signaling in colon cancer cells, and in turn, Wnt signaling modifies metabolism of cancer cells. This metabolic transition directs tumor-promoting changes in the microenvironment.

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 Program Highlight  

Cancer Prevention & Prognosis (CPP)

McLarenMercolaMcClelland
Program Leaders: Christine McLaren, PhD, and Dan Mercola, MD, PhD
Theme Leader: Michael McClelland, PhD


Basic laboratory science, clinical, epidemiologic, quantitative, and public health disciplines are represented within the Cancer Prevention & Prognosis (CPP) membership. As indicated by their departmental affiliations, the members cover a broad spectrum of expertise. Members in the basic sciences are in the fields of developmental and cell biology, microbiology, molecular genetics, and molecular biology and biochemistry. Members in clinical areas are in the fields of medicine, ophthalmology, obstetrics & gynecology, pathology, pediatrics, urology, radiation oncology. Members also participate in additional disciplines that include biostatistics, community and environmental health, epidemiology, and public health.

The CPP Program fosters interactions between members within our program and those within other programs. Certainly projects have benefited from both inter- and intra disciplinary skills of members. To aid interactivity, the program continues to feature symposia and retreats. One of the highlights of this program is the ongoing and extremely successful Distinguished Speaker Series. The series invites internationally recognized scientists in cancer research to present innovative science. On average, three to five scheduled speakers are co-sponsored with the Genetic Epidemiology Research Institute per year and the series is organized so that after the seminar presentation, time is scheduled for individual investigators or small groups of researchers to meet with the presenter, fostering interdisciplinary research and collaborations.

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 Shared Resource Highlight  

In each issue of CAncer REsearch, we take an in-depth look at one of the seven core facilities supported by the cancer center. We also have a quarterly shared resources
e-newsletter that contains important updates from all our shared resources. If you would like to receive our Shared Resources newsletter in your inbox, please send an email with “Shared Resources Newsletter” in the subject line to tidball@uci.edu

Biobehavioral Shared Resource Facility (BBSR)
Director: Lari Wenzel, PhD
Facility Manager: Susie Hsieh, PhD

Wenzel The Biobehavioral Shared Resource Facility (BBSR) continues to assist Dr. Jason Zell’s (CPP) “Phase 2A Clinical Biomarker Trial of Aspirin and Arginine Restriction in Colorectal Cancer Patients” trial. The BBSR worked with Zell to develop a psychosocial telephone counseling intervention for an integrative oncology project that examines the effects of oral aspirin taken daily with an arginine-restricted diet on certain colorectal cancer biomarkers in treated colorectal cancer patients. The director and co-director of the BBSR, as well as a clinical psychologist, devoted time and expertise to this study and used patient reported outcomes to assess the effectiveness of patient telephone counseling (PTC) for the intervention arm of this clinical trial.

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 Disease Oriented Team (DOT) Highlight  

Prostate DOT (P-DOT)

AhleringKelly

 




Co-leaders: Thomas Ahlering, MD, and Michael McClelland, PhD

Dr. Sheldon Greenfield (CPP) presented “Prostate Cancer Clinical Research at UC Irvine” at the July Prostate DOT meeting. Greenfield deals with the methodology of clinical trials in comparative effectiveness research studies by following people after their trial and looking at the SEER database. Greenfield’s questionnaire consists of combinations of questionnaires, medical records information and claims data to “fill in some of the gaps.” With this information, Greenfield can predict which treatment patients will get by the information obtained, in addition to their personal characteristics. For example, if a person has a high PSA, the standard next step is to get a biopsy. However, the need for surgery may be eliminated after reviewing the results of the questionnaire. Following Greenfield’s presentation, John Murray, PIO/media relations manager, announced that the renal and cryoablation protocols with Dr. Jamie Landman (SPT) will be promoted in the fall and published in Men’s Magazine. Wendy Lynch, cancer registry director, presented, “What the UC Irvine Cancer Registry Can Do for You.” Cancer registry services are available to our members and we recommend that you get your requests in early for your protocol needs. During our September meeting it was noted that Dr. Ed Uchio has joined the Urology faculty from Cedars Sinai where he opened 27 clinical trials in the past year. Gregory Weiss, PhD (CSB), presented his development of nanodevices used to detect early stages of cancer. Weiss would like to collaborate with members to submit a Program Project Grant application to the NIH in 2015. And finally, Dr. James Ward announced “Movember,” a program that will bring attention to both prostate and testicular cancers during the month of November. To do this, Ward encourages the faculty and staff to grow a mustache in support of this event. If anyone is interested in participating or joining, please contact Dr. Ward at jeward@uci.edu.

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 Congratulations!  


Zhao Zhao awarded $567,000 for breast cancer research
UC Irvine researcher Weian Zhao, PhD (OIB), has received a grant of $567,373 to develop new treatments to cure metastatic breast cancer. Zhao will use the funds, awarded by the U.S. Army Medical Research and Materiel Command, to create bioengineered mesenchymal stem cells, or MSCs. These stem cells are currently used in experiments to treat a variety of diseases and they produce very few side effects. Zhao's study is the first of its kind aimed at developing more effective treatments with MSCs targeting metastatic breast cancers that spread to the lungs. Zhao, a member of the Chao Family Comprehensive Cancer Center and the Sue and Bill Gross Stem Cell Research Center, believes this approach will offer patients a new kind of therapy without the debilitating side effects commonly experienced with chemotherapy.

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WenzelWenzel gets $1.9 million to create ovarian cancer app
Lari Wenzel, PhD (CPP), UC Irvine professor of medicine and public health, has received a $1.9 million from the Patient-Centered Outcomes Research Institute to create and study the use of a new, personalized approach to shared treatment decision-making for newly diagnosed ovarian cancer patients. Wenzel will lead the effort to develop and test a tablet computer app that will help newly diagnosed ovarian cancer patients learn about and understand the trade-offs among chemotherapy options. Wenzel will collaborate with Dana Mukamel, Robert Bristow, MD (CPP), and Kathryn Osann, PhD (AS), of UC Irvine, and clinicians from several universities and cancer centers across the country, in addition to ovarian cancer stakeholder groups such as the National Ovarian Cancer Coalition, In My Sister’s Care and the Ovarian Cancer National Alliance. The project is part of a portfolio of patient-centered research that addresses PCORI’s national research priorities and will provide patients with information to help them make better-informed decisions about their care.

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AhleringDr. Thomas Ahlering awarded 2013 translational device-based research grant
The Institute for Clinical and Translational Science (ICTS) announced Dr. Thomas Ahlering (CPP) as a recipient of a translational device-based research grant. This ICTS program focuses on new devices that are used in the promotion of human health, such as in the diagnosis or treatment of human disease. The current award recipients involve devices that are undergoing a new stage of development, for example, from the lab to first time in humans, from pilot human studies to a formal clinical trial, or from clinical experience to commercial development. Ahlering’s device-based research, “Pelvic Tissue Cooling during Hypothermic Robotic Radical Prostatectomy: Simulation and MRI Thermal Measurement for effective improvement in patient Quality of Life outcomes," was one of only two projects awarded.

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 New Faces  
Please join ws in welcoming our new cancer center members!


Carmichael
Dr. Joseph Carmichael is an assistant clinical professor in the Department of Surgery. Carmichael started the first robotic rectal surgery program in the state of Missouri and specializes in both laparoscopic and robotic surgical approaches to diseases of the colon and rectum. He is a member of the American Society of Colon and Rectal Surgery and participates on two of its national committees. His cancer research interests include surgical colorectal cancer outcomes and multimodality treatment of rectal cancer. Carmichael has been appointed as an associate member of the cancer center.

Chessler
Dr. Steven Chessler is an associate professor in the Division of Endocrinology interested in the biology of the endocrine pancreas. Chessler’s focus is on the pancreatic islets and the insulin-producing beta cells. Gaining an understanding of these cells is important for diabetes and also has direct relevance to insulinoma and other neuroendocrine cancers: indeed, much of his work utilizes insulinoma-derived cells. Chessler is interested in pancreatic islet/beta cell imaging; such technology could aid in the localization of insulinoma and other neuroendocrine tumors. His work toward gaining a better understanding of pancreatic islet, beta cell and insulimona cell development and function could yield new targets for the treatment of glucagonoma, insulinoma and other neuroendocrine cancers; Chessler has been appointed as a full member in the Systems, Pathways & Targets Program.

Fleischman
Dr. Angela Fleischman is an assistant professor in the Division of Hematology-Oncology focused on identifying the molecular mechanisms that control the evolution of hematopoietic stem cell clones. Using myeloproliferative neoplasms (MPN) as a model disease, she is currently working to identify defects in the stem cell pool that antedate the appearance of neoplastic stem cells. Fleischman proposes that establishment of neoplastic clones is largely a Darwinian process in which somatic mutations “rescue” an unfit stem cell leading to the establishment of a selective advantage. Evolution of acute leukemic clones as an adaptive response in an unfit stem cell pool is well established in the setting of overt bone failure but fitness defects of this kind have not, until recently, been sought in MPN cells. She has developed a non-canonical model of leukemogenesis in MPN where neoplastic clones evolve as an adaptive response of unfit stem cells in the pre-neoplastic state. Fleischman has been appointed as a full member in the Systems, Pathways & Targets Program.

Jeyakumar
Dr. Deepa Jeyakumar is an assistant clinical professor in the Division of Hematology-Oncology with a focus of advanced hematologic malignancies. She has conducted retrospective studies on patients with malignant hematologic diseases that are difficult to treat with current therapies. Her current research interests include investigation of novel therapies in leukemia in older patients. The clinical outcomes of elderly patients with acute myelogenous leukemia are extremely poor. Frequently, AML in elderly patients has evolved out of antecedent hematologic diseases, especially myelodysplastic and myeloproliferative diseases. They have acquired additional cytogenetic changes that deem their disease more difficult to treat. The most effective initial therapy for younger patients with AML is induction chemotherapy which requires that the patient have good organ function and good functional status. Elderly patients with AML frequently are not eligible for induction chemotherapy because they do not fulfill these criteria. This is an area that is in need of therapies that are effective and tolerable. Current investigations are ongoing in search for novel agents for this patient population. To date, there are few agents are particularly effective. This would be a great area to investigate novel agents as there is a clear need for more effective therapies. Jeyakumar is interesting in designing and participating in clinical trials that investigate novel agents. Jeyakumar has been appointed as an associate member of the cancer center.

Klempner
Dr. Samuel Klempner is an assistant clinical professor in the Division of Hematology-Oncology. Klempner’s research interest is focused on the identification and development of targeted therapies in human malignancy with a focus on the phosphoinositide-3-kines (PI3K) pathway in gastric, esophageal, and lung cancer. He is interested in the study of mechanisms of resistance to targeted therapies and the rational design of early phase clinical trials to delay resistance and maximize efficacy to targeted therapies. During his research experience in the signal transduction laboratory of Dr. Lewis Cantley, he was familiarized with molecular and cell biology techniques to study targeted therapies and resistance in-vitro and in human tumor samples. To prepare for a career as a translational investigator Klempner completed the year-long clinical investigator course at Dana Farber Cancer Institute and the translational medicine course through the Harvard Catalyst program. He plans to incorporate the study of tumor signaling changes and mutational data into the choice of targeted therapies with the hope that understanding both mutational and signaling data will not only improve our biologic understanding, but also improve patient outcomes through more personalized therapeutic choices. Klempner has been appointed as a full member in the Systems, Pathways & Targets Program.

Liu
Chang Liu, PhD, is an assistant professor in the Department of Biomedical Engineering and a faculty member in the UC Irvine Center for Complex Biological Systems. Liu has two interests in cancer research. The first is in the evolution of sulfated antibodies against proinflammatory chemokines involved in cancer metastasis. His lab is interested in using phage display to evolve antibodies against cancer-upregulated chemokines such as SDF-1. However, there is a key challenge associated with this strategy: the chemokine/receptor interaction relies on posttranslational tyrosine sulfation of the receptor, and it has been demonstrated for nearly all chemokine receptors studied that these sulfates are essential for binding between chemokines and their cognate receptors. Therefore, one would expect any high-affinity antibody against a chemokine to require tyrosine sulfates to capture the natural mode by which chemokines are bound by their receptors. Yet standard phage display does not allow the evolution of sulfated proteins and peptides as sulfation is a posttranslational modification. In Liu’s lab, he has demonstrated the successful production of multiple-sulfated antibodies in E. coli using an expanded genetic code that achieves the co-translational incorporation of sulfotyrosine into any site in a protein. His lab has also shown that these antibodies can be displayed on bacteriophage M13. Therefore, he is able to create large libraries of sulfated antibodies and use phage display to isolate ones that target various chemokines involved in cancer. Liu believes these libraries will be especially well-suited to the discovery of high-affinity, high-specificity, anti-chemokine antibodies that are not addressable with standard phage display methods. Liu’s other cancer research area is understanding the evolution of dysregulated signaling networks in the presence of inhibitors. His lab recently developed a parallelizable, continuous, in-vivo evolution system in yeast that allows any gene or set of genes to be experimentally evolved very rapidly in the laboratory. Liu plans to use this system to evolve, in a high-throughput manner, kinase networks in the presence of different kinase inhibitors. This will provide insights into how dysregulated signaling networks at the heart of many cancers can evolve around inhibited nodes, and whether certain nodes or inhibitors are superior in preventing the evolution of resistance. Liu has been appointed as a full member in the Chemical Structural Biology Program.

McEligot
Archana J. McEligot, PhD, is a nutritional epidemiologist and professor of health science at California State University, Fullerton. McEligot’s primary research interests include examination of the association between dietary intakes and cancer prevention and outcomes in at-risk populations. Also, she is interested in assessing the relationship between dietary circulating biomarkers, such as folate and carotenoids in conjunction with genetic polymorphisms on cancer outcomes. McEligot is the recipient of the National Cancer Institute’s Career Development Award investigating the interaction between DNA repair genes and diet on breast cancer risk. Results suggest that folic acid supplementation significantly influences circulating total and folate vitamer concentrations. Further, total folate concentrations at and/or after breast cancer diagnosis were positively associated with overall survival. Preliminary epigenetics data suggest a significant association between MTHFR loci and breast cancer outcomes, as well as independent associations between DNA repair loci and diet on cancer survival. Other research projects include assessing behavior and beliefs related to food choice in at-risk native Hawaiians in Southern California, as well as assessing dietary intakes and physical activity in Pacific Islander youth. Also, McEligot has recently been awarded two USDA external grants on workforce and curriculum development with CSUF students, garnering over a total of $1 million in research funding. She has extensive experience in curriculum development, guiding students and helping diverse students succeed. McEligot has taught nutrition-related topics to undergraduate, graduate and medical students and has mentored nearly 30 students in research projects since 2006; two of her students have been recognized for outstanding theses, and several have co-published and/or presented at scientific meetings. She has also been recognized by CSUF’s honor society as an outstanding faculty member for involving students in research. McEligot has been appointed as a full member in the Cancer Prevention & Prognosis Program.

Parang
Keykavous Parang, PharmD, PhD, is the associate dean of research, graduate studies and global affairs at Chapman University. In addition, he is a professor in the School of Pharmacy, Chapman University. Parang’s research can be appropriately described as the application of chemistry in anticancer drug design and delivery. The emphasis of his research lies at the interface between chemistry and biology. Specific areas currently under investigation include (1) using peptides as cell-penetrating molecular transporters in anticancer drug delivery; (2) designing protein kinase inhibitors as anticancer agents; (3) development of multifunctional anticancer agents; (4) synthesis and evaluation of modified nucleosides and nucleic acids; and (5) designing peptide nanomaterials for tissue engineering and nanomedicine. One area currently under investigation is to block enzymes called protein kinases that are overproduced or over-activated in a number of cancers, such as colon, breast, lung, hepatic, and pancreatic tumors. Blocking the activated protein kinases by specific inhibitors is expected to slow down or stop the growth of cancer cells but have minor or no effect on normal cells, making such inhibitors effective drugs with little side effects. Another objective of Parang’s laboratory is to design chemical tools to deliver anticancer agents specifically to tumors. Parang's laboratory designs peptide nanomaterials for applications in anticancer drug delivery. The objective of this project is to design and evaluate peptide nanomaterials as cell-penetrating nuclear targeting agents and molecular transporters of bioactive cell-impermeable anticancer compounds. This study will document the potential for new hybrid peptide-drug assemblies that may be used for the non-covalent or covalent targeted delivery of bioactive molecules including cell-impermeable compounds with biological significance. Furthermore, the tools are designed to improve the cellular uptake of anticancer agents. His research has been supported by the American Cancer Society and the National Science Foundation. Parang has been appointed as an associate member of the cancer center.

Vanderwal
Christopher Vanderwal, PhD, is a professor in the Department of Chemistry at UC Irvine. Vanderwal specializes in organic synthesis, with a focus on complex, bioactive natural products. Most of the natural products that his group targets have potential anti-cancer activity. Most have simply been tested for cytotoxicity against a limited panel of cell lines, so little is known about selectivity profile and even less about mechanism of action. His aim is to develop laboratory syntheses of these molecules that could permit more in-depth analysis of their biological properties and mechanism of action, as well as the development of structure/activity relationships. Vanderwal has been appointed as a full member in the Chemical Structural Biology Program.