Molecularly Intertwined: City of Hope and Caltech Collaborate to Fight Leukemia and Autoimmune Disease

October 10, 2017 | by Wayne Lewis

Leukemic cells | City of Hope Leukemic cells
Scientists, physicians and supporters recently gathered for an annual symposium shining a light on the Caltech-City of Hope Biomedical Research Initiative. The partnership combines the strengths of these top Southern California research institutions to accelerate scientific investigations and fight disease.
 
At Caltech’s Beckman Institute building on Monday, Oct. 9, guests heard welcome remarks from Robert W. Stone, president and chief executive officer of City of Hope, and Thomas F. Rosenbaum, Ph.D., president, holder of the Sonja and William Davidow Presidential Chair and professor of physics at the California Institute of Technology (Caltech).
 
The collaboration at the heart of the partnership is designed to speed up basic scientific discovery and its translation into better treatments, diagnostic tools and prevention strategies. To stimulate the exchange of ideas between City of Hope and Caltech, the initiative provides seed grants for studies uniting investigators from both institutions.
 
This partnership was established in 2008 with funding from City of Hope, Caltech and an anonymous lead donor. It has backed 47 pilot programs to date — many of them going on to earn sustaining government grants.
 
The 2017 symposium, dubbed “Molecularly Entwined,” showcased a pair of projects fueled by the Caltech-City of Hope Biomedical Research Initiative.
 

Leukemia, Aging and a Complicated Gene

WenYong Chen, Ph.D., associate professor of cancer biology at Beckman Research Institute of City of Hope, and Caltech professor of chemistry André Hoelz, Ph.D., described a joint project that ultimately may help ward off leukemia — as well as declines that come with age.
 
WenYong Chen, Ph.D. WenYong Chen, Ph.D.
The two scientists are zeroing in on a gene called SIRT1. The function of the enzyme encoded by SIRT1 is complicated, contradictory and not fully understood in humans. The protein is believed to help extend the longevity of cells under stress, but in abundance it is associated with cancer.
 
Previous studies by Chen and his colleagues have shown that activating the SIRT1 pathway can promote cancer in blood stem cells and aid leukemia in resisting chemotherapy. His lab also has found that, inversely, suppressing the pathway’s action depletes cancerous blood stem cells and makes leukemia vulnerable to chemotherapy. Meanwhile, a study led by Hoelz — a Heritage Medical Research Institute investigator at Caltech and faculty scholar of the Howard Hughes Medical Institute — revealed the crystal structure of the human SIRT1 enzyme.
 
Teaming up, Chen and Hoelz seek to uncover fully how the gene relates to the development of blood stem cells, the process of aging and the progress of aggressive blood cancers. New therapies that fight leukemia and impede aging could emerge from what they learn.
 

When the Body Attacks Itself

Zuoming Sun, Ph.D., professor of molecular immunology at at Beckman Research Institute of City of Hope, and Ellen Rothenberg, Ph.D., Caltech’s Albert Billings Ruddock Professor of Biology, delved into their collaboration exploring certain cells of the immune system and diseases such as arthritis, lupus and multiple sclerosis.
Zuoming Sun Bio Portrait Zuoming Sun, Ph.D.

T cells are the hunters and helpers among the body’s natural defenses against disease. In some autoimmune diseases, however, these cells can turn against the body itself, identifying healthy tissue as foreign and attacking. 
 
The partnership between Sun and Rothenberg links complementary expertise: He studies mature T cells and the part they play in the immune system, while she studies the path that leads stem cells to grow into T cells.
 
Together, Sun, Rothenberg and their colleagues have found that mature T cells exhibit a kind of long-term molecular memory. The action of TCF-1, a protein involved in their early development, influences their patterns of response later along — including activity that renders adults susceptible to autoimmune disease. The scientists’ fundamental insights could lead to treatments for autoimmune conditions spurred by rogue T cells.
 
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