Congratulations to Giuseppina Claps, a student in the Sanford-Burnham Graduate School of Biomedical Sciences, on receiving one of ten nationally competitive 2013 Research Scholar Awards from the Joanna M. Nicolay Melanoma Foundation (JMNMF)! These $10,000 grants support exceptional graduate student research in melanoma.
Giuseppina Claps received her JMNMF award at a special recognition ceremony. She is pictured here with her mentor Ze'ev Ronai (left) and Robert Rickert (right), associate dean of the Sanford-Burnham Graduate School of Biomedical Sciences.
Siah2 levels (brown staining) are high in human castration-resistant prostate cancer (left), as compared to benign prostate growths (right)
Researchers discover that a protein called Siah2 helps prostate cancer cells resist hormone therapy—making it an attractive biomarker and therapeutic target.
Hormonal therapies can help control advanced prostate cancer for a time. However, for most men, at some point their prostate cancer eventually stops responding to further hormonal treatment. This stage of the disease is called androgen-insensitive or castration-resistant prostate cancer. In a study published March 18 in Cancer Cell, a research team found a mechanism at play in androgen-insensitive cells that enables them to survive treatment. They discovered that a protein called Siah2 keeps a portion of androgen receptors constantly active in these prostate cancer cells. Androgen receptors—sensors that receive and respond to the hormone androgen—play a critical role in prostate cancer development and progression.
Pedal the Cause–San Diego, the region’s only multi-day cycling fundraiser for cancer research, will announce their first annual event today at 11 a.m. PT, on our La Jolla campus.
Sanford-Burnham is excited to be part of this new fundraising event for cancer research, in partnership with our two “neighbor” National Cancer Institute (NCI)-designated cancer centers, UC San Diego Moores Cancer Center and the Salk Institute for Biological Studies.
Ze'ev Ronai, Ph.D.
Editor’s note: below is a message that Kristiina Vuori, M.D., Ph.D., our President and Interim CEO, sent to Sanford-Burnham scientists and staff today.
Dear All:
I’m pleased to announce the appointment of Dr. Ze’ev Ronai to the position of Scientific Director of the La Jolla campus. As many of you are aware, such position was held by Dr. John Reed in 1995-2001, while I held a similar position of Executive Vice President for Scientific Affairs prior to my appointment as President in 2010.
Fabian Filipp, Ph.D.
Meet Fabian V. Filipp, Ph.D., M.Sc., a researcher in the NCI-designated Cancer Center and a 2009 recipient of the Institute’s Fishman Fund Awards.
On Memorial Day, members of our military—including those who have sacrificed their lives or have returned to us with injuries or illness—will receive much-deserved thanks and recognition. Whether you attend a parade, observe a moment of silence for those lost, or simply shake a soldier’s hand and say, “thank you,” you will find your way of expressing your gratitude. At Sanford-Burnham, we support the U.S. armed services by doing what we do best: science.
Sanford-Burnham’s headquarters in San Diego County place it in the midst of one of the largest active duty military populations in the country and the largest concentration of soldiers wounded in combat. Additionally, both states where Sanford-Burnham has locations, California and Florida, are among those with the largest populations of veterans. So the men and women who defend us are always on our minds. In honor of Memorial Day weekend, we have chosen to highlight some of the ways we strive to defend them in return.
Meet Eric Lau, Ph.D., a postdoctoral researcher in Sanford-Burnham’s NCI-designated Cancer Center.
Kristiina Vuori, M.D., Ph.D., Institute president and director of Sanford-Burnham's NCI-designated Cancer Center (center), with NCI-CBC leadership and participants
Where do new medicines come from? The first step in the drug discovery process often involves screening small molecules (chemicals) to determine their potential to produce innovative biological research tools. Sanford-Burnham’s Conrad Prebys Center for Chemical Genomics uses robotic technology to sift through chemical compounds by the millions to find the few that could potentially be developed into new medicines
Fresno State faculty member Jason Bush and one of his former students, Shana Morshedian, now a research assistant in John Reed's lab.
Last week, faculty from California State University, Fresno (Fresno State) and Sanford-Burnham met to define the next steps in the Collaborative Project in Cancer Health Disparities Research.
Sanford-Burnham, Fresno State, and the Central Valley Health Policy Institute share this collaborative project, funded by the National Cancer Institute. Their mission is to train undergraduate and graduate students for future cancer research careers and enhance cancer research potential at Fresno State (a minority-serving institution). The three-year grant gives Fresno State minority students the opportunity to spend a summer in Sanford-Burnham laboratories, where they become more familiar with biomedical research.
Human squamous carcinoma cells with ATF2 (green) located at mitochondria (red) after exposure to genotoxic stress. Nuclei are shown in blue.
The National Cancer Institute (NCI) estimates that as many as one in 51 men and women will be diagnosed with melanoma—the deadliest form of skin cancer—at some point during their lifetimes. A research team led by Ze’ev Ronai, Ph.D. is working to unravel the molecular mechanisms underlying the development and progression of this disease in hopes of improving prevention and treatment strategies. To do this, Ronai’s laboratory has been studying a protein named Activating Transcription Factor 2 (ATF2), which is associated with poor prognosis in melanoma. ATF2 is a two-faced protein—in melanoma cells, it’s oncogenic, or cancer-causing, while in non-malignant types of skin cancers, it acts as a tumor suppressor.
In a paper published February 3 in the journal Cell, the team identified a molecular switch that controls ATF2’s dual functions. This switch is controlled by protein kinase Cɛ (PKCɛ), which disables ATF2’s tumor-suppressing activities, sensitizing cells to chemotherapy; instead, ATF2’s tumor-promoting activity is enhanced. The team also found that high levels of PKCɛ in melanoma are associated with poor prognosis.
Mitochondria are often called cellular “powerhouses” because they convert nutrients into energy. But these tiny structures also help determine cellular lifespan. Scientists are now discovering how mitochondria alternate between duplicating and fragmenting and how these events help cells adapt to diverse physiological conditions.
In a paper published November 18 in Molecular Cell, a team led by Dr. Ze’ev Ronai discovered that the protein Siah2 regulates mitochondrial fragmentation under low oxygen conditions. The significance of these findings is demonstrated by the heart’s response to oxygen shortage and ischemia, the tissue damage caused by lack of oxygen, when the researchers inhibited Siah2. In cells and mice lacking the protein, heart cell death was prevented. As a result, tissue damage was reduced in a mouse model that mimics a heart attack.
Dr. Judith Bond (right), professor and department chair at Penn State College of Medicine and president-elect of the Federation of American Societies for Experimental Biology (FASEB), visits a poster at the 2011 International Proteolysis Society meeting.
Scientists from around the world met in San Diego October 16-20 to discuss their work on proteases at the International Proteolysis Society’s bi-annual meeting. The event, organized by Sanford-Burnham’s Dr. Guy Salvesen and Stanford University’s Dr. Matt Bogyo, brought together more than 300 researchers from a wide variety of fields to provide educational, training, and networking opportunities at all levels.
Proteolysis is a basic cellular function in which enzymes (called proteases) cleave other proteins. Sometimes a cell needs proteases to stop an aberrant protein from sending the cell astray. Other times, proteolytic cleavage activates a protein, cutting it free from an anchor that was holding it back. Needless to say, proteolysis needs to be carefully regulated, as it affects everything from cellular movement to cell lifespan.
Crystal Structure of Anthrax Lethal Factor complexed with a small molecule inhibitor
As the United States pauses to observe the 10th anniversary of the September 11th terrorist attacks, we reflect on the research advances that contribute to new counterterrorism measures—understanding anthrax, for example—and the health of our soldiers in Iraq and Afghanistan, including under-studied conditions such as traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD). Here are a few examples, and these only cover discoveries made at Sanford-Burnham since September 11, 2001. Can you think of more? Please share your thoughts in the comments below.
Dr. Mei-fan Chen, member of Dr. Ze'ev Ronai's lab
When a protein isn’t folded correctly, it can’t function properly. This has the potential to wreak havoc on a cell – and a person. The underlying cause of cystic fibrosis provides a good example of how even a small mistake in protein folding can lead to a big health problem. In this disease, a person inherits a mutated gene encoding a protein called CFTR. Because of this mutation, CFTR is not folded into its proper shape. The cell degrades the misfolded protein, leading to poor lung function, digestive problems and other complications.Most protein folding problems occur when the endoplasmic reticulum (ER) is stressed. The ER is a cellular organelle that specializes in folding proteins that are destined to be anchored in the cell surface or secreted. When the ER’s load of unfolded or misfolded proteins outweighs its ability to fix them, ER stress can result. The cell is usually able to correct this problem by triggering the unfolded protein response. This process slows protein production, enhances protein folding, and clears away any that have been misfolded. ER stress also slows the process of cell division.
“Although it has been observed that ER stress halts cell reproduction, it is not well understood how and why this happens,” explains Dr. Mei-Fan Chen, who recently received her Ph.D. from UC San Diego for research she conducted in Dr. Ze’ev Ronai’s lab.
Sanford-Burnham scientists are leading several exciting symposia over the next few months. Please follow the links below for more event and registration information.
2011 Signaling, Metabolism and Hypoxia Symposium
Chaired by Dr. Ze’ev Ronai
May 6, 2011, 2:00 – 5:30 p.m. (PDT)
Sanford-Burnham Medical Research Institute
10901 North Torrey Pines Road
La Jolla, California
2011 Glycobiology Gordon Research Conference
Chaired by Dr. Hudson Freeze
May 8 – 13, 2011
Il Ciocco Hotel
Lucca (Barga), Italy
Sanford-Burnham’s 33rd Annual Symposium: Structural Systems Biology
Chaired by members of the Bioinformatics and Systems Biology Program
Drs. Adam Godzik, Dorit Hanein, Andrei Osterman, Niels Volkmann
June 7, 2011, 9:00 a.m. – 5:15 p.m. (PDT)
Hilton La Jolla Torrey Pines
La Jolla, California
Cardiomyocyte Regeneration and Protection
Chaired by Dr. Mark Mercola
Sponsored by Abcam
June 20 – 21, 2011
Hilton La Jolla Torrey Pines
La Jolla, California
2011 Molecular Therapeutics of Cancer Research Conference
Chaired by Dr. Sara Courtneidge
Sponsored by the Cancer Molecular Therapeutics Research Association
July 10 – 14, 2011
Asilomar Conference Center
Pacific Grove, California
Seventh General Meeting of the International Proteolysis Society
Chaired by Dr. Guy Salvesen and Dr. Matthew Bogyo
October 16 – 20, 2011
Hilton San Diego Resort and Spa
San Diego, California