SDSC/UCSD Study Uncovers Mechanisms of Cancer-Causing Mutations

Computer modeling leads to more precise targeting of therapies —

Researchers at the San Diego Supercomputer Center (SDSC) and the Moores Cancer Center at the University of California, San Diego, have described for the first time the molecular mechanism of cancer development caused by well-known “resistance” mutations in the gene called epidermal growth factor receptor (EGFR).

While these mutations were known for quite a long time, the question as to why they cause cancer or make some drugs ineffective was still not answered.

The study, called “Molecular Determinants of Drug-Specific Sensitivity for Epidermal Growth Factor Receptor (EGFR) Exon 19 and 20 Mutants in Non-Small Cell Lung Cancer,” and published online in the journal Oncotarget, demonstrates how computer modeling of EGFR mutations found in lung cancer can elucidate their molecular mechanism of action and consequently optimize the selection of therapeutic agents to treat patients. … Read the full story from the UC San Diego Newsroom


Dr. Razelle Kurzrock

Dr. Razelle Kurzrock

The senior investigator in the study was Razelle Kurzrock, MD. Dr. Kurzrock is Chief of the Division of Hematology & Oncology; Murray Professor of Medicine; Senior Deputy Director, Clinical Science and
Director, Center for Personalized Cancer Therapy and Clinical Trials Office at the UC San Diego Moores Cancer Center.

Lyudmila A. Bazhenova, MD, associate professor of medicine and leader of the Lung Cancer Unit Team at the Moores Cancer Center, was also an investigator in the study.

Read the study report (UC San Diego only)

Doctorate Program Will Study Substance Abuse and Its Consequences

Collaboration between UC San Diego and SDSU among first in nation —

A new Joint Doctoral Program (JDP) in Interdisciplinary Research on Substance Use has been launched by the Division of Global Public Health in the University of California, San Diego School of Medicine and San Diego State University’s School of Social Work. The program will emphasize research devoted to studying the use and misuse of alcohol and drugs – and related social and health consequences. … Read the full story from the UC San Diego Newsroom


Dr. Steffanie Strathdee

Dr. Strathdee.

Co-directors of the program are Steffanie Strathdee, PhD, and Maria Luisa Zúñiga, PhD.

Dr. Strathdee is Associate Dean of Global Health Sciences, head of the UC San Diego Global Health Initiative and Harold Simon Professor and Chief of the Division of Global Public Health at UC San Diego.

Dr. Zúñiga is associate professor and behavioral epidemiologist in the Division of Global Public Health and associate professor in the San Diego State University School of Social Work.

Read the joint doctoral program catalog description

Medtech Meets Cleantech: Malaria Vaccine Candidate Produced from Algae

Cheap, green technique advances efforts toward malaria transmission vaccine in humans —

Researchers at University of California, San Diego School of Medicine used algae as a mini-factory to produce a malaria parasite protein. The algae-produced protein, paired with an immune-boosting cocktail suitable for use in humans, generated antibodies in mice that nearly eliminated mosquito infection by the malaria parasite. The method, published Feb. 17 by Infection and Immunity, is the newest attempt to develop a vaccine that prevents transmission of the malaria parasite from host to mosquito. … Read the full story from the UC San Diego Newsroom


Dr. Joseph VinetzStudy senior author Joseph Vinetz, MD, is professor of medicine in the Division of Infectious Diseases.

Read article abstract

UC San Diego Researchers Develop Efficient Model for Generating Human Stem Cells

Approach has potential to simplify generation of iPSCs for use in human stem cell therapies

Researchers at the University of California, San Diego School of Medicine report a simple, easily reproducible RNA-based method of generating human induced pluripotent stem cells (iPSCs) in the August 1 edition of Cell Stem Cell. Their approach has broad applicability for the successful production of iPSCs for use in human stem cell studies and eventual cell therapies. … Read the full story from the UCSD Newsroom


Four Department of Medicine researchers are coauthors of the study report in Cell Stem Cell:

Citation for the study report: Naohisa Yoshioka, Edwige Gros, Hai-Ri Li, Shantanu Kumar, Dekker C. Deacon, Cornelia Maron, Alysson R. Muotri, Neil C. Chi, Xiang-Dong Fu, Benjamin D. Yu, Steven F. Dowdy. Efficient Generation of Human iPSCs by a Synthetic Self-Replicative RNA. Cell Stem Cell – 1 August 2013 (Vol. 13, Issue 2, pp. 246-254)  |  Read the report

Studies Suggest New Key to “Switching Off” Hypertension

A team of University of California, San Diego researchers has designed new compounds that mimic those naturally used by the body to regulate blood pressure. The most promising of them may literally be the key to controlling hypertension, switching off the signaling pathways that lead to the deadly condition. … Read the full story from the UCSD Newsroom


Senior author of the study report is Daniel T. O’Connor, MD, professor of pharmacology and professor of medicine in the Division of Nephrology-Hypertension. O’Connor directs the UC San Diego Hypertension Research Program and Hypertension Research Group.

Laboratory test tubesOther Department of Medicine coauthors are Sushil K. Mahata, PhD, professor of medicine and pharmacology; and project scientist Nilima Biswas, PhD. Mahata is also a Veterans Affairs San Diego Healthcare System investigator.

Citation for the study report:  Igor F. Tsigelny, Valentina L. Kouznetsova, Nilima Biswas, Sushil K. Mahata, Daniel T. O’Connor, Development of a pharmacophore model for the catecholamine release-inhibitory peptide catestatin: Virtual screening and functional testing identify novel small molecule therapeutics of hypertension, Bioorganic & Medicinal Chemistry, Available online 17 July 2013, ISSN 0968-0896, http://dx.doi.org/10.1016/j.bmc.2013.07.008. |  Full text (UCSD only)

Herpes Virus Exploits Immune Response to Bolster Infection

Researchers at the University of California, San Diego School of Medicine and colleagues report that the herpes simplex virus type-1 (HSV-1), which affects an estimated 50 to 80 percent of all American adults, exploits an immune system receptor to boost its infectivity and ability to cause disease. … Read the full story from the UCSD Newsroom


Dr. Richard Gallo

Dr. Richard Gallo

Richard L. Gallo, MD, PhD, left, is principal investigator of the study, which is reported in the online-only journal Nature Communications.

Gallo is professor of medicine and chief of the Division of Dermatology.

Citation for the study report:  Daniel T. MacLeod, Teruaki Nakatsuji, Kenshi Yamasaki, Lester Kobzik & Richard L. Gallo. HSV-1 exploits the innate immune scavenger receptor MARCO to enhance epithelial adsorption and infection. Nature Communications 4, Article number: 1963. doi:10.1038/ncomms2963. Published 06 June 2013.  |  Abstract

More Information:

Cholesterol Sets Off Chaotic Blood Vessel Growth

A study at the University of California, San Diego School of Medicine identified a protein that is responsible for regulating blood vessel growth by mediating the efficient removal of cholesterol from the cells. Unregulated development of blood vessels can feed the growth of tumors.  … Read the full story from the UCSD Newsroom


Dr. Yury MillerYury Miller, MD, PhD, left, is senior author of the study report. He is associate professor of medicine in the Division of Endocrinology & Metabolism and faculty member in the Biomedical Sciences Graduate Program.

He first joined UC San Diego as a postdoctoral fellow in Dr. Joseph Witztum’s laboratory in 1998.

Miller is principal investigator of a National Institutes of Health R01 research grant, “Zebrafish Models of Vascular Inflammation and Atherosclerosis,” and a subproject of a P01 research program project with the La Jolla Institute of Allergy & Immunology, “Oxidized lipids and endotoxemia in vascular inflammation.”

Longhou Fang, PhDFirst author Longhou Fang, PhD, left, is a postdoctoral fellow in the Miller laboratory. He is the recipient of a National Institutes of Health K99 postdoctoral award for the project, “AIBP-mediated cholesterol efflux and angiogenesis.”

The other coauthors excepting Drs. Ulrich and Torres-Vásquez are affiliated with the Department of Medicine.

Dr. Philipp Wiesner.

Second-year internal medicine resident Philipp Wiesner, MD, right, who chose Miller as one of his mentors for the investigations he performed during his residency program research rotation, presented data from the vascular inflammation project at Medicine Grand Rounds on May 15.

Wiesner is also a coauthor of the study reported in Nature.

Citation for the study report:  Longhou Fang, Soo-Ho Choi, Ji Sun Baek, Chao Liu, Felicidad Almazan, Florian Ulrich, Philipp Wiesner, Adam Taleb, Elena Deer, Jennifer Pattison, Jesús Torres-Vázquez, Andrew C. Li & Yury I. Miller. Control of angiogenesis by AIBP-mediated cholesterol efflux. Nature (2013) doi:10.1038/nature12166. Published online 29 May 2013.  |  Read the full text (UCSD only)

More Information

Other UC San Diego news stories about Miller’s work:

Philipp Wiesner’s May 15 Medicine Grand Rounds presentation “Oxidized Phospholipids in Inflammation and Atherosclerosis”  |  Watch video (UCSD only)

Tumor-Activated Protein Promotes Cancer Spread

Researchers at the University of California, San Diego School of Medicine and UC San Diego Moores Cancer Center report that cancers physically alter cells in the lymphatic system – a network of vessels that transports and stores immune cells throughout the body – to promote the spread of disease, a process called metastasis.  … Read the full story from the UCSD Newsroom


Dr. Judith VarnerJudith Varner, PhD, is senior author of the study report. She is professor of medicine in the Division of Hematology-Oncology and an investigator in the Solid Tumor Therapeutics Program at the UC San Diego Moores Cancer Center.

Citation for the study report:
PI3Kα activates integrin α4β1 to establish a metastatic niche in lymph nodes. Barbara Garmy-Susini, Christie J. Avraamides, Jay S. Desgrosellier, Michael C. Schmid, Philippe Foubert, Lesley G. Ellies, Andrew M. Lowy, Sarah L. Blair, Scott R. Vandenberg, Brian Datnow, Huan-You Wang, David A. Cheresh, and Judith Varner. PNAS 2013 ; published ahead of print May 13, 2013, doi:10.1073/pnas.1219603110  |  Abstract  |  Read the article (PDF) (UCSD only)

UC San Diego Named 15th Best Research University in the World for Scientific Impact

Geisel Library, UC San Diego

Geisel Library, UC San Diego

In a global ranking designed to provide highly accurate measurements of the scientific impact of universities and their contributions to scientific collaboration, the University of California, San Diego is ranked the 15th best research university in the world. … Read the full story from the UCSD Newsroom


Monoclonal Antibody Targets, Kills Leukemia Cells

Researchers at the University of California, San Diego Moores Cancer Center have identified a humanized monoclonal antibody that targets and directly kills chronic lymphocytic leukemia (CLL) cells…. Read the full story from the UCSD Newsroom


Dr. Thomas KippsThomas Kipps, MD, PhD, Evelyn and Edwin Tasch Chair in Cancer Research, is principal investigator of the study, which was reported in the Proceedings of the National Academy of Sciences.

Kipps is professor of medicine in the Division of Hematology-Oncology and deputy director of research at the UCSD Moores Cancer Center.

Citation for the published study: Zhang S, Wu CCN, Fecteau J-F, Cui B, Chen L, Zhang L, Wu R, Rassenti L, Lao F, Weigand S, Kipps TJ. Targeting chronic lymphocytic leukemia cells with a humanized monoclonal antibody specific for CD44  PNAS 2013; published ahead of print March 25, 2013, doi:10.1073/pnas.1221841110  |  Read the abstract