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Left to right: Quinn Deveraux, John Timmer, and Brendan Eckelman
Brendan Eckelman, Quinn Deveraux, and John Timmer are three Sanford-Burnham alumni who turned to the entrepreneurial side of science, with a goal to translate research findings into new therapies. Eckelman (2003-2007) and Timmer (2004-2009) both conducted their graduate research in Guy Salvesen’s laboratory, while Quinn Deveraux was a postdoctoral fellow (1996-2000) in the laboratory of Sanford-Burnham’s CEO, John C. Reed. During their time at Sanford-Burnham, all three made contributions to the apoptosis field—the study of programmed cell death, a process that can malfunction in cancer and other diseases.
After earning his Ph.D., Eckelman joined Deveraux’s group at the Genomics Institute of the Novartis Research Foundation (GNF). At GNF they were tasked with generating therapeutic antibodies for the Novartis pipeline. Ready to leave the pharma environment in late 2009, the two were introduced to Mark Lappe by Reed. Shortly thereafter, Eckelman, Deveraux, and Lappe founded Inhibrx, a biotechnology company dedicated to discovering new therapeutic antibodies for cancer, inflammatory diseases, and metabolic disorders.
Inhibrx focuses on one of the biopharma industry’s greatest needs—translation of validated and novel drug targets into clinical candidates.
Guy Salvesen, Ph.D.
Meet Guy Salvesen, Ph.D., professor and director of the Apoptosis & Cell Death Program in Sanford-Burnham’s National Cancer Institute-designated Cancer Center.
Sharon Schendel, Ph.D., former postdoctoral researcher at Sanford-Burnham and head of the Biochemical Journal's U.S. editorial office
How cells traffic nutrients and wage immune responses, how they repair themselves and self-destruct to save their neighbors, how they guard against disease and proliferate in the developing organism – it all comes down to a complex network of biochemical signals and how they’re regulated from moment to moment and cell to cell. Understanding the intricate genetic and chemical pathways inside a cell can help biologists and medical professionals better understand how to pinpoint where signaling has gone haywire, diagnose the onset of disease early, and develop and administer targeted therapeutic drugs.
Cell signaling and regulation was the topic of a symposium on March 22 at Sanford-Burnham’s La Jolla campus, where the sponsor of the meeting, the Biochemical Journal, a publication of the British Biochemical Society, has had its U.S. editorial offices since 2001. Discussions at the symposium, which focused on cell signaling and regulation as it relates to cancer, featured talks from eight Biochemical Journal editorial board members, as well as researchers John Reed and Sara Courtneidge from Sanford-Burnham, and Tony Hunter from the nearby Salk Institute
Since 2001, Sanford-Burnham has been home to the U.S. editorial office of the Biochemical Journal, a publication of the Biochemical Society. Guy Salvesen, Ph.D., professor and director of the Apoptosis & Cell Death Program in Sanford-Burnham’s National Cancer Institute-designated Cancer Center, is a vice chair on the journal’s editorial board.
In gratitude to Sanford-Burnham, the Biochemical Journal is sponsoring a special one-day symposium in March, with Dr. Salvesen as host.
What: Cell Signaling and Regulation symposium
Where: Sanford-Burnham Medical Research Institute, La Jolla, Calif., Building 12 (map)
When: Thursday, March 22, 2012, 9 a.m. – 4:30 p.m. PT
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.
Even though a large portion of the research work at Sanford-Burnham historically has been carried out by postdoctoral trainees, graduate students have always had a presence at the Institute. In the past, these individuals were officially enrolled at UC San Diego or other universities and carried out their research in a lab at Sanford-Burnham because of its particular expertise. Although this type of arrangement still continues, the situation changed in 2006 when the Institute founded its own graduate training program designed to confer Ph.D. degrees. The Graduate School of Biomedical Sciences at Sanford-Burnham was recently recognized by the Western Association of Schools and Colleges (WASC) as a Candidate for Accreditation.*
According to the Dean of the program, Dr. Guy Salvesen, “Our eventual goal of full accreditation will serve as proof of what we already know; namely, that a Ph.D. degree from the Institute is a rigorous one of high quality that stacks up well against a degree from any of the other outstanding institutions that students might choose.”
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.
Dr. Mihee Kim, new postdoc in Dr. Robert Oshima's lab
Editor’s note: We often hear how important it is to make a good first impression. We thought it would be interesting to learn about newcomers’ first impressions of Sanford-Burnham, so we interviewed some new employees who each play a different role at the Institute’s La Jolla campus.
One of our most recent employees, Dr. Mihee Kim, has been a postdoctoral associate in Dr. Robert Oshima’s lab since June of this year. From previous positions at Harvard and NIH, Mihee had experience both with stem cells and with proteins that bind to nucleic acids (such as DNA). She is combining those disciplines in the Oshima lab’s attempt to understand the role of the Ets2 transcription factor (a protein that controls the expression of other genes) in the behavior of cancer stem cells. Mihee had heard of Sanford-Burnham because a former Harvard colleague, Dr. Dieter Wolf, took a position as professor here in 2007. She had no preconceived impressions of the Institute, but has been pleased to learn that our claims of having a collaborative culture are not overstated. Being somewhat new to working with animal models, Mihee has already established interactions with postdocs in several Institute labs to develop a robust system for identifying intestinal stem cells. She has also found the imaging and flow cytometry shared services to be very effective resources for interaction and for providing both training and expert analysis.
Most amazing, she says, is the fact that, “people actually respond in a helpful way to e-mail requests for advice and reagents. I never had that experience before!”
Mihee is excited about the freedom she has been given by Dr. Oshima to explore multiple aspects of Ets2/cancer stem cell function according to her own curiosity and intuition.
Sophisticated proteomics equipment can now determine virtually the entire protein complement of a cell.
Every day we gain a better understanding of how cells work. In the past 20 years, new tools to examine gene expression and function have illuminated many different mechanisms that guide all aspects of cellular behavior. However, to fully understand normal cellular functions and how they malfunction in disease, we need more in-depth information about the many proteins our genes produce. Which proteins are being produced? How are they modified? What is each protein’s ultimate function and how do they interact on a system-wide level?
New technologies in the proteomics facility at Sanford-Burnham are providing reams of data that could help answer these and many other questions. In a room full of advanced technology, the Thermo LTQ-Orbitrap Velos mass spectrometer system stands apart. The system has been part of the proteomics toolbox for about a year and has proven its value identifying proteins several times over.
Dr. Laurence Brill, director of Advanced Proteomics in Sanford-Burnham’s Proteomics Facility, notes that the Velos system is 10 times more sensitive and three times faster than previous machines, but there’s a lot more to the core’s success than the excellent equipment. “We use very stringently applied analytical methods that take years to develop and refine,” says Dr. Brill. “We are thinking very carefully about the goals and biology of each assay and making them reproducible from run to run.”
Dr. Kristiina Vuori and Dr. John Reed are working to find new ways to help cancer cells die.
May is National Cancer Research Month, created by Congress in 2007 to recognize the American Association of Cancer Research (AACR) for its contributions to the field. To honor AACR and highlight some of the important cancer research being done at Sanford-Burnham, throughout May we posted a series of articles on the ongoing work in our National Cancer Institute-designated Cancer Center. The vast majority of this research is made possible by funding from the National Institutes of Health (NIH), which includes the National Cancer Institute (NCI).
Cells contain a complex mixture of opposing forces striving for balance. When these mechanisms work properly, cells are healthy. However, if one side gains the upper hand, balance is lost and disease can result.
Programmed cell death, or apoptosis, is a critical cellular quality control mechanism regulated by small squads of pro- and anti-apoptotic proteins. In healthy cells, these opposing mechanisms maintain the life/death balance. However, they can also go awry in a number of diseases. In particular, cancers often over-express anti-apoptotic proteins, giving them a measure of immortality.
Sanford-Burnham’s NCI-designated Cancer Center has led the way on cell death research. In a recent paper, Dr. Guy Salvesen, who directs the Apoptosis and Cell Death Program, and colleagues showed how an enzyme, caspase-8, can teeter between advancing or defeating apoptosis, depending on factors in the cell. Caspases are critical regulators of apoptosis, and understanding their function could lead to new treatments.
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
Dr. Guy Salvesen
Cells come and go throughout our lifetime. Some live a long time (like brain cells), while others constantly grow, divide and die. Cell death is a process that must be carefully managed – too many cells dying in the brain leads to neurodegenerative diseases like Alzheimer’s, while not enough cell death allows tumors to form. But not all cell death is the same. Apoptosis, often called “programmed cell death”, is neat and clean – seppuku-style cell suicide. Necrosis, on the other hand, is the messy, unplanned version of cell death – the kind that might cause pain and swelling.
Apoptosis begins by activating enzymes known as caspases, setting the cell on the path towards death – a good thing if they are cancer cells or cells infected with a virus. One caspase, known as caspase-8, is a double agent of apoptosis – depending on the conditions, it can promote either cell death or cell survival. What makes caspases-8 choose a side? A new study led by Dr. Douglas Green at St. Jude Children’s Research Hospital and Sanford-Burnham’s Dr. Guy Salvesen points the finger at a protein called FLIPL. Their study was published online March 2 in the journal Nature.
“We’ve known for some time that caspase-8 can play this dual role, but we didn’t know the molecular basis for the opposing functions. Knowing the mechanism may allow us to design therapies to defeat a cancer cell’s quest for immortality,” says Dr. Salvesen, director of the Apoptosis and Cell Death Research Program and dean of the Graduate School of Biomedical Sciences at Sanford-Burnham.