Stalking a Killer
Proteomics research offers promise for cancer treatment
When a Federal Express delivery arrives at the Prince William Campus, it’s not always your typical package. It might include a tissue biopsy from someone undergoing treatment for lung cancer at M.D. Anderson Cancer Center in Houston, Texas, or a blood specimen from a patient suspected of having ovarian cancer at Memorial Sloan-Kettering Cancer Center in New York City.
Doctors at these and other premier medical institutions are turning to Mason’s Center for Applied Proteomics and Molecular Medicine for explanations to complex medical puzzles so they can better evaluate and treat their patients’ illnesses.
A New Paradigm for Personalized Medicine
The Center for Applied Proteomics and Molecular Medicine, part of the Life Sciences initiative in the College of Arts and Sciences, is directed by Lance Liotta, formerly of the National Cancer Institute, and Emanuel Petricoin III, who came to the university from the U.S. Food and Drug Administration.
Proteomics—the study of protein activity in cells—is an emerging field in biomedical research. It holds the promise of a future where the individuality of a patient’s disease state will determine tailored therapies and personalized management. “Patient-tailored medicine is the future of clinical practice,” says Liotta.
To accelerate the center’s work, Mason and Inova Health System have created a unique partnership that moves cutting-edge discoveries and technologies directly to patient management and care through clinical trials and patient-tailored research at the bedside.
Proteomics Research at Mason
An estimated 400,000 to 10 million different proteins (the proteome) perform cellular functions in the 20,000 to 25,000 genes that construct the human genome. In contrast to the static nature of the genome, the dynamic proteome—the working machinery of the cell—is constantly changing in response to tens of thousands of signals from inside and outside the cellular environment.
The pioneering research led by Liotta and Petricoin focuses on the analysis of the molecular pathways in diseased tissue to determine individualized and targeted treatment for patients. The team has developed proteomic technologies that can identify diseased pathways, which help predict which patients will respond to treatment and why.
“But proteomics can go beyond a prediction and help us understand which pathways to pursue in patients who, based on that prediction, are destined to fail conventional therapies,” says Petricoin.
The researchers are also looking to discover and identify proteins in the blood that may be markers for early disease detection, prognosis, and treatment. The team recently discovered an archive of protein fragments in blood that may be disease markers, including a specific fragment of a gene associated with an inherited risk for ovarian and breast cancer. The findings were published in the October issue of Clinical Chemistry.
“Although we have suspected the existence of these fragments in the past, this is the first study where we have actually identified and named the molecules,” Liotta says. “This gives us an untapped source of proteins from diverse tissue and cellular origin that may offer vital disease-related information.”
Tools for a Healthier Tomorrow
Liotta and Petricoin have developed and implemented numerous groundbreaking scientific principles and proteomic technologies since they began their collaborative research in 1997:
- Use of mass spectrometry, a technology that can rapidly sort molecules based on size and other properties, to generate potentially diagnostic proteomic fingerprints that identify and quantify disease-specific proteins
- Discovery of molecular “mops” that harvest disease markers in the blood and are naturally occurring blood-borne molecules that bind to disease-related markers not previously known to exist
- Use of reverse phase protein microarray technology, which takes thousands of cells from a tiny biopsy specimen and produces a detailed quantitative analysis of the cellular circuitry, to identify a hyperactive pathway that is a new target for therapy and can predict patient response to chemotherapy for rhabdomyosarcoma, a highly aggressive form of childhood cancer
- Use of laser capture microdissection to rapidly pluck microscopic diseased cells directly from a biopsy sample, which segregates the cells of the evolving disease for analysis and leaves behind unnecessary cellular information (Liotta and colleagues at the National Cancer Institute several years ago invented laser capture microdissection, a commercialized technology that is widely used in laboratories throughout the United States.)
Along with cancer, many human diseases, such as diabetes, obesity, and cardiovascular conditions, are underpinned by deranged pathways, explains Liotta. “We think the development of new proteomic technologies will help uncover new drug targets, or pathways that respond to treatment, for critical areas other than cancer,” he says.
Lance Liotta and colleague Virginia Espina use laser microdissection to segregate diseased cells from other cellular material in a tissue biopsy.
Researchers at the Center for Applied Proteomics and Molecular Medicine: (left to right, seated) Julie Wulfkuhle, Robyn Araujo; (standing) Valerie Calvert, Espina, Liotta, Emanuel Peticoin III, David Geho