'State of the Hutch'

During Tuesday evening’s State of the Union address, President Barack Obama called for Congress to restore funding for basic research. “Congress should undo the damage done by last year's cuts to basic research so we can unleash the next great American discovery,” he said.

That’s a hope echoed by researchers and key staff at Fred Hutchinson Cancer Research Center in Seattle who, when asked about the “State of the Hutch”, said limited funding is the biggest obstacle they face this year.

“The biggest challenges are and have always been the lack of external funding to explore the numerous ideas that spring out of our diverse laboratories,” said Raquel Sanchez, administrator for the Human Biology Division at Fred Hutch.

Fred Hutch President and Director Dr. Larry Corey said that’s a key reason why diversifying funding sources is critical to the organization’s ongoing success.

“Increasing public support of research is needed to move our innovations and science forward, and to continue to support and recruit the incredible research stars we have at the Hutch,” he said.

Some of the latest strategies aimed at driving future growth include the recent launch of Juno Therapeutics Inc., a new biotechnology company co-founded by Hutch scientists; last August’s inaugural Obliteride bicycling fundraising event; and a potential state ballot initiative to fund cancer research. “Miracles still come from the lab,” Corey said. Healthy funding streams are essential to keep up with the promising ideas constantly emerging from research teams who are committed to saving lives and who start each day believing that the next discovery is just waiting to be made.

As he noted in an address to employees last December, “One can be nothing but optimistic” about the current State of the Hutch.

In response to questions about the State of the Hutch, here’s what representatives from various divisions around the Center said are their biggest obstacles and aspirations for the coming year:

What are some of the research highlights you’re expecting to come out of your division this year, and how could they help us understand the mechanisms behind cancer and other diseases, or lead to better methods of prevention, screening or treatment?

Breast Cancer: “Using global approaches, made possible by developments in microarray technology and the identification of genes in the Human Genome Project, we are now in a position to elucidate the molecular components -- and the connections between the components -- that coincide with the acquisition of malignant traits. We are conducting discovery projects in studies of precursor and malignant lesions that will help to better understand and respond appropriately to the clinical heterogeneity of breast cancer.” (Human Biology Division)

Brain Cancer: “We have begun to catalog cancer-specific molecular vulnerabilities in glioblastoma stem cells in "compare-and-contrast" studies with non-transformed neural stem cells, which are candidate cells-of-origin for glioblastoma. These studies have led to the identification of novel therapeutic strategies for glioblastoma, which are being pursued in collaboration with Dr. Jim Olson of the Clinical Research Division.” (Human Biology Division)

Human microbiome: “We expect breakthrough activities in our microbiome research that promise to advance our understanding of the role of the human microbiome in hematopoietic cell transplantation outcomes that impact patient survival.” (Vaccine and Infectious Disease Division)

Prostate Cancer: “We are studying the causal mechanisms responsible for initiation and progression of human prostate cancer. In addition, we developed and characterized a small-molecule Hepsin inhibitor, which is now undergoing an animal prostate cancer trial." (Human Biology Division)

Expanding stem cells in cord blood: “Dr. Colleen Delaney, the director of the Cord Blood Transplant Program at Fred Hutch, has developed a revolutionary new technique using Notch-ligand stimulation that rapidly expands cord blood progenitor cells 164-fold, resulting in successful and rapid engraftment and making cord blood transplants a safe, effective possibility for adults who do not have human leukocyte antigen-matched siblings available for stem cell transplantation.” (Clinical Research Division)

Lung Cancer: “We are working toward translating increased understanding of the basic biology of squamous cell lung cancer driver genes to the development of novel therapies for humans with the disease. We aim to test the effectiveness of these new therapeutic strategies using improved mouse models." (Human Biology Division)

Global oncology: “We are building upon Uganda Cancer Institute/Hutch alliance’s achievement on global oncology and expanding our cancer care impact to other regions and countries in Africa. We are also completing a new ambulatory care, research, and training facility in Kampala, Uganda to further research in global oncology and infection-related cancers, and build capacity in clinical care, diagnosis, and research-based treatments.” (Vaccine and Infectious Disease Division)

Herpesvirus: “Human cytomegalovirus, a member of the herpesvirus family, typically produces few if any symptoms in otherwise healthy individuals, but it often causes life-threatening infections in newborns, recipients of solid organ and hematopoietic stem cell transplants, and other immunocompromised patients. Current efforts aim to elucidate the activities of the various domains of these genes and to identify other viral and cellular factors needed to maintain the robust protein synthetic capacity in cytomegalovirus-infected cells.” (Human Biology Division)

Targeting cancerous cells, protecting healthy ones from chemotherapy: “Dr. Jim Olson is developing a fundamentally new class of anti-cancer compounds, called "optides," which are engineered to specifically attack cancerous cells while leaving healthy cells untouched. This approach is expected to have a markedly enhanced “therapeutic window” compared to traditional chemotherapies.” (Clinical Research Division)

H. pylori: “H. pylori, a bacterium that lives in the gut, has a relatively small genome that contains approximately 1,500 genes. It had been long observed that H. pylori clinical isolates are heterogeneous at the sequence level. Using an H. pylori microarray we showed that this variability extends to the presence and absence of whole genes. We further showed that even in the context of a single human stomach there exist multiple clones with unique gene complements. We are currently investigating how this diversity is generated and the consequences of this diversity on patient outcomes.” (Human Biology Division)

Preventing HIV: “We have opened in Cape Town, South Africa, a 10,000-square-foot laboratory that will focus on vaccine research to prevent HIV and related infectious diseases worldwide. This immunology laboratory will contribute to the advancement of a successful HIV vaccine in sub-Saharan Africa.” (Vaccine and Infectious Disease Division)

Preventing mother-to-child HIV transmission: “In partnership with clinicians within the Kenya Research Program, the HIV lab is studying antiviral drug resistance, with an emphasis on resistance that develops in the setting of prevention of mother-to-child transmission and in adults who use antiretroviral drugs for prophylaxis. Another major effort of these studies is developing HIV assays to detect diverse HIV variants circulating in Africa. Current work aims to reveal how the transmitted variants "escape" from maternal immune pressure and elucidate whether functional characteristics of maternal antibodies from the blood and breast milk compartments are associated with risk of transmission.” (Human Biology Division)

Immunotherapy: “The Clinical Research Division has initiated an exciting new research program utilizing adoptive T-cell immunotherapy of malignancies utilizing genetically modified T lymphocytes that possess an enhanced ability to recognize and kill cancer cells. One iteration of this approach utilizes ’chimeric antigen receptors,‘ or CARs, which recognize the CD19 antigen on B-cell lymphomas and chronic lymphocytic leukemia. This program is spearheaded by Drs. Stan Riddell, Cameron Turtle, and David Maloney. Ongoing clinical trials using CD19-CAR modified T cells have already shown dramatic tumor responses.

“A second T-cell therapy approach utilizes T lymphocytes expressing an optimized T-cell receptor that recognizes the WT-1 antigen expressed by myeloid leukemias and some other tumor types. These studies are under the leadership of Drs. Philip Greenberg, Merav Bar, and Aude Chapuis.  Drs. Riddell, Greenberg and Larry Corey have formed a spinoff biotech corporation, called Juno Therapeutics, that has licensed some of the novel technology developed by Drs. Riddell and Greenberg and represents one of the most exciting opportunities arising from Fred Hutch in recent years.

“A third separate but parallel approach using T-cell immunotherapy is being explored by Drs. Brian Till and Oliver Press, who are developing chimeric-antigen receptor-modified T cells targeting the CD20 antigen expressed by B-cell lymphomas. Their construct also incorporates an inducible Caspase 9 suicide gene to allow regulated elimination of the modified T cells in case unanticipated toxicities are encountered. Clinical trials of the latter approach are not yet available.”  (Clinical Research Division)

Gene therapy: “Dr. Hans Peter Kiem, an internationally renowned gene-therapy researcher, has engineered a special ‘chemotherapy-resistance‘ gene into hematopoietic stem cells to protect them from damage by common chemotherapy drugs such as temozolomide and BCNU (bis-chloroethylnitrosourea), which is used to treat patients with an aggressive form of brain cancer known as glioblastoma.  A small clinical trial using high-dose chemotherapy with temozolomide and BCNU for glioblastoma patients has shown promising initial results. Kiem also is planning a study of patients with AIDS-related lymphomas who will receive blood stem cells with two inserted genes: one that counteracts the HIV infection and one that protects the patient from chemotherapy’s effects.” (Clinical Research Division)

What are the biggest challenges facing your division this year?

“Diminishing federal funding from the National Institutes of Health for biomedical research undoubtedly represents the biggest challenge and threat for 2014. Investigators are finding it increasingly difficult to get their grants renewed. Even when grants are funded, the budgets are routinely slashed to levels that make it difficult to do the proposed research.” (Clinical Research Division)

“The biggest challenges are and have always been the lack of external funding to explore the numerous ideas that spring out of our diverse laboratories. NIH awards are systematically cut every year they are funded, making it progressively more challenging to deviate from stated aims and explore new territory as it is discovered. Thankfully the Hutch has always been supportive of innovative science and open to alleviating funding gaps.”  (Human Biology Division)

“Conducting HIV clinical trials of all worthy candidate vaccines with greatly reduced budgets.” (Vaccine and Infectious Disease Division)

“Maintaining and growing our excellent science during this period of reduced NIH funding.” (Vaccine and Infectious Disease Division)

“Finding effective ways to leverage public and private partnerships to turn many of the strategic opportunities, both domestic and international, into project realities.” (Vaccine and Infectious Disease Division)

What keeps researchers in your division motivated to do this work?

“The motivation comes from two areas: the pure love of deconstructing the complexities of human biology by running the next experiments that lead to the next exciting questions, and being able to contribute to the larger goal of curing human diseases.” (Human Biology Division)

“Our firm belief that through our international collaborative research efforts, we will move forward more aggressively in developing a preventive efforts and a vaccine against HIV.” (Vaccine and Infectious Disease Division)

“The opportunity to be involved in doing meaningful work and improving outcomes of cancer patients with infections.” (Vaccine and Infectious Disease Division)

“Researchers in the Clinical Research Division are motivated by their fascination with the basic biologic processes that underlie the development and progression of malignancies and by the desire to develop reliable, nontoxic, curative therapies for these devastating diseases.” (Clinical Research Division)