Translational Research at UCSD: Dr. Catriona Jamieson Talks about a New Kind of Teamwork

Dr. Catriona JamiesonJust upstairs from her patient clinic at the Moores UCSD Cancer Center, physician-scientist Dr. Catriona Jamieson works to identify and test new treatments in her laboratory.

The closeness of clinic and laboratory is intentional. The Moores UCSD Cancer Center is designed to support translational researchers like Dr. Jamieson, whose work is inspired and directed by her patients’ needs.

“Our patients are the drivers for our research,” she says. “In my clinic, I get to see how courageous my patients are and what an uphill battle it is.”

Catriona H. M. Jamieson, M.D., Ph.D., is Assistant Professor of Medicine in the Division of Hematology-Oncology and director for Stem Cell Research at the Cancer Center. She is a respected researcher and a vibrant advocate for her patients’ quality of life.

“My mandate is to find
more selective,
less toxic therapies.”

In a recent interview, she talked about how the spirit of collaboration – with a focus on the patient – is transforming academic and pharmaceutical medicine here at UCSD.

“The goal is to empower patients”

Dr. Jamieson specializes in myeloproliferative disorders (MPDs) and leukemia. Myeloproliferative disorders are a family of uncommon but not rare degenerative disorders in which the body overproduces blood cells.

Myeloproliferative disorders can cause many forms of blood clotting including heart attack, stroke, deep venous thrombosis, and pulmonary emboli and can develop into acute myelogenous leukemia.

Although some effective treatments are available, they are laden with serious side effects. In addition, individuals can become resistant to the treatments.

Dr. Jamieson studies the mutant stem cells and progenitor cells in myeloproliferative disorders. These cells can give rise to cancer stem cells.Cancer stem cells may lie low to evade chemotherapy and then activate again later, causing disease progression and resistance to treatment.

“We want
to change cancer…
and take away
the fear.”

“My mandate,” she says, “is to find more selective, less toxic therapies.“The goal is to empower patients to define their lives by what they want, not by what they’ve been diagnosed with.”

The evolution of new hope

In the past year, Dr. Jamieson’s stem-cell research studies have taken a great leap: from identifying a promising treatment in the laboratory to opening the first clinical trial in humans.

The clinical trial is the fruit of teamwork that has brought together her discoveries in myeloproliferative disorders and a local pharmaceutical company’s drug development track.

In both her laboratory work and the clinical trial, Dr. Jamieson has collaborated with TargeGen, a privately-held San Diego pharmaceutical company, and stem-cell researchers at the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University.

Myeloproliferative disorders come from a genetic mutation in the Janus kinase 2 (JAK2) pathway of blood cell production. In 2006, Dr. Jamieson and her colleagues discovered exactly where this mutation first starts skewing the blood cell manufacturing process – in the hematopoietic stem cells.

The report was published in the Proceedings of the National Academy of Sciences.

This discovery identified JAK2 as a target for possible new stem-cell therapies for myeloproliferative disorders. At the same time, TargeGen had a JAK2 inhibitor called TG101348 in drug development.

Read the report
in the Proceedings
of the National Academy
of Sciences

(free full text)

Ida Deichaite, Ph.D., Director, Office of Industry Relations for the Cancer Center, and John Hood, Ph.D., Director of Research at TargeGen, worked with Dr. Jamieson to launch a collaborative research project.TargeGen made the inhibitor available to Dr. Jamieson and her colleagues, who tested it in a laboratory model of a myeloproliferative disorder known as polycythemia vera (PV).

The results indicated that TG101348 was specifically effective, and not toxic, in its action against polycythemia vera. Corroborating data came from an independent Harvard group of researchers led by D. Gary Gilliland, M.D., Ph.D.

Drs. Jamieson and Gilliland, who agreed to co-submit their reports, published their data side by side in the journal Cancer Cell in April 2008.

Read the abstract
of the report
in Cancer Cell

Clinical trial now underway

The first clinical study of TG101348 opened at UCSD and five other centers early this year. The study, an FDA Phase I/II trial, is testing the compound for its safety and efficacy in individuals who have myeloproliferative disorders. Patients from UCSD are now enrolled.

The hope is that TG101348 will halt or even reverse the disease process.

“If we suppress the mutant gene,” Dr. Jamieson says, “We can get people back into feeling like they don’t have the disease. We try to go back to early phases of the disease and reverse the effects.”

If the early results bear out, the treatment will be available as a pill. The study may also lead to more broadly useful therapies.

“It’s a testament to teamwork,” she says.

“Like soccer — we all
play our positions,
and pass the ball
back and forth.”

Funding for the TG101348 studies came from a variety of public and private sources, including the Cancer Center, the California Institute for Regenerative Medicine (CIRM), and a private donor who is himself affected by a myeloproliferative disorder.

Dr. Jamieson’s patients supported the study as well.

“They stepped up,” she says. “They offered to donate blood and bone marrow samples.”

Dr. Jamieson has just received a three-year, $3 million New Faculty II Grant from the California Institute for Regenerative Medicine for her studies of leukemic transformation in myeloproliferative disorders.

Read the
public abstract
for Dr. Jamieson’s
CIRM research
project

Began stem cell research with Dr. Irving L. Weissman at Stanford

Dr. Jamieson earned her Ph.D. in Microbiology from the University of British Columbia in Vancouver in 1992. Inspired to be a scientist, she had a passion for patient care as well; she earned her M.D. at the University of British Columbia in 1995.

She went on to complete her medical internship and residency training there.

After beginning a fellowship in bone marrow transplant at the Vancouver General Hospital/British Columbia Cancer Agency, she transferred to Stanford University in Palo Alto, California in 1999. There, she completed her bone marrow transplant fellowship and a fellowship in hematology.

Dr. Jamieson started her stem cell research at Stanford in 2001, when she joined the laboratory of stem cell research pioneer Irving L. Weissman, M.D.

Dr. Weissman is Director of the Institute of Stem Cell Biology and Regenerative Medicine at Stanford. He and his group illuminated the stem-cell pathway that produces blood cells.

In Dr. Weissman’s laboratory, Dr. Jamieson and her research team were the first to identify the cancer stem cell in chronic myelogenous leukemia (CML). They published their results in the New England Journal of Medicine in 2004.

Read the
New England Journal
of Medicine
article
(free full text)

In 2003, Dr. Jamieson became an instructor in the Division of Hematology at Stanford.She joined the UCSD faculty as Assistant Professor of Medicine in the Division of Hematology-Oncology in 2005, and became Director of the Cancer Center’s Stem Cell Research Program in 2006.

“An ideal environment” for translational research

With laboratories, clinics, and core facilities sharing a single building, the Cancer Center is an ideal translational research environment, Dr. Jamieson says.

Cancer Center Director Dennis A. Carson “always approaches things as if he were the patient,” she says.

“He had a vision that translational studies could be done here very well and in an innovative way.”

“Here, the investment is in people.”

She credits Dr. Ken Kaushansky, Helen M. Ranney Professor and Chair of the Department of Medicine, with ensuring that researchers have the protected time and the startup funding for their research.

“Here, the investment is in people,” she says. “Not only in funding, but also in being there for you.”

Since she joined UCSD in 2005, Dr. Jamieson has assembled a collaborative group to share ideas and resources in stem cell research. Called the La Jolla Cancer Stem Cell Working Group, it includes stem cell biologists from a number of major research institutions including UCSD, Salk, Burnham Institute, Scripps Research Institute.

“Like soccer,” she says. “We all play our positions, and pass the ball back and forth.”

Dr. Jamieson reflects upon the meaning of the name “La Jolla” – “the jewel.”

“The jewel is the talent here,” she says. “To have a team that is responsible, reliable, and enthusiastic — that is everything.”

And the goal is to meet the patients’ needs.

“We want to change cancer,” she says, “so that it can be treated like a chronic disease — and take away the fear.”

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