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Q&A: How evolutionary biologists got lucky with a sperm discovery

Drs. Harmit Malik and Mia Levine on a male fruit fly protein necessary for embryo survival

July 7, 2015 | By Dr. Rachel Tompa / Fred Hutch News Service

Fruit fly sperm

Evolutionary biologists at Fred Hutchinson Cancer Research Center discovered a unique protein in fruit fly sperm essential for embryo growth. From left to right, fruit fly sperm in the male reproductive system, after insemination in the female reproductive tract, and inside a fertilized fruit fly egg.

Courtesy of Dr. Mia Levine

Gestation has traditionally been viewed as the mother’s domain, with dad doing little more than depositing his half of the genome. Now, a new study in fruit flies pinpoints a protein in sperm that regulates embryos’ earliest cell divisions.

Evolutionary biologists at Fred Hutchinson Cancer Research Center published a study Tuesday in the journal eLife showing that when dad flies are missing this protein, known as HP1E, fertilized eggs die before they can even hatch. The findings could point to new ways to study fertilization in humans and other animals.

In most cells of the body, be they fruit fly or human, DNA is packaged by a special set of proteins into an organization system known as chromatin. Think of chromatin as your cellular closet organizer: This highly ordered structure winds, loops and squishes the six feet of DNA that is your entire genome into its microscopic housing in every cell, known as nuclei.

If most of your nuclei are like a well-organized closet, sperm nuclei are more like a jam-packed storage unit. Unlike most cells, sperm don’t need to do anything with their DNA other than deliver it to the egg.

HP1E appears to help solve an unusual problem of sperm-meets-egg fertilization: That super-packed DNA has to be quickly unbundled and reformatted into the “normal” chromatin within mere minutes inside the egg before the embryo can begin to grow and divide in a process known as mitosis. How HP1E does this is still somewhat of a mystery, especially since the protein itself is not actually present during the unpacking step, but the discovery of a male protein involved in early embryo survival is somewhat surprising, the researchers said.

We sat down with two of the study authors, Drs. Harmit Malik and Mia Levine, to find out more about protein evolution, fruit fly sex and what their findings could mean for human fertility. Their answers have been edited for clarity and brevity.

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From lemon juice to plastic forks: Quick tricks to deal with cancer treatment side effects

Patients and their care providers share the workarounds they’ve devised to handle the worst of chemo, radiation and surgery

July 6, 2015 | By Rachel Tompa / Fred Hutch News Service

Cancer can change the body's response to food in many ways

Cancer treatment can change the body's response to food in many ways. Favorite foods, like ice cream, can taste completely different.

Illustration by Kimberly Carney

When Dr. Carla Kakutani was in the thick of her first go-round of chemotherapy, it was a struggle to figure out her daily meals. She was diagnosed with stage 4 metastatic breast cancer two years ago and her doctors started her on a chemo regimen with some brutal side effects.

Kakutani, a primary care doctor in Winters, California, developed oral thrush, which made her mouth so sensitive that she had a hard time eating anything with texture, and the things she could eat tasted totally different.

“I love food so this was definitely the hardest part of treatment for me,” Kakutani said. “Everything just tasted like cardboard. Sawdust.”

After trying out different foods that hurt too much to eat or didn’t appeal to her temporarily scrambled taste buds (even ice cream was intolerable), Kakutani found she could stomach cereal or graham crackers soaked in milk until they were soft and mushy.

“It was kind of comforting, like a little kid food,” she said.

Many people with cancer, such as Kakutani, have had to come up with their own tried-and-true ways to combat cancer treatments’ common and difficult side effects like “chemo mouth,” nausea, fatigue, neuropathy and more.

In some cases, there may be medical options regarding ways to help manage side effects so it’s always good to check with your provider, but we wanted to hear patients’ – and their loved ones’ and care providers’ – favorite workarounds. We asked and you responded via Facebook, Twitter, email, through interviews and more. To find out some of the best suggested “hacks” to combat side effects, read on: 

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Skin cancer: 9 things to know to lower your risk

From cover-ups to caffeine, here are some tips for protecting your skin during the summer and all year long

July 2, 2015 | By Dr. Rachel Tompa / Fred Hutch News Service

Sunbathers on the beach

The how-to’s of skin cancer prevention haven’t changed much in recent years — avoid too much ultraviolet light via sun or tanning beds and take care not to burn or tan — but that message is clearly not reaching enough people, according to Fred Hutch researchers.

Stock photo by FeaturePics

With climbing rates of skin cancer in the U.S., including the deadly form, melanoma, it’s time to get serious about prevention, experts say.

The how-to’s haven’t changed much in recent years — avoid too much ultraviolet light via sun or tanning beds and take care not to burn or tan — but that message is clearly not reaching enough people, said Fred Hutchinson Cancer Research Center cancer prevention researcher Dr. Margaret Madeleine.

A recent study by researchers from the Centers for Disease Control and Prevention found that nearly 5 million U.S. adults are treated every year for all types of skin cancer to the tune of $8.1 billion. Melanoma rates have doubled in this country since 1982, according to a CDC report earlier this month. The majority of these cancer cases are preventable.

Last summer, the U.S. Surgeon General issued a call to action to prevent this too-common disease: Non-melanoma skin cancers, chiefly basal cell carcinoma and squamous cell carcinoma, are the most common cancers in this country by far, afflicting an estimated 4.3 million people per year.

That report, the first time the surgeon general had come out against sunbathing and tanning beds, is a great step, Madeleine said. But we need to do more.

“The message needs to be louder,” Madeleine said. “There are some really serious public health tactics that could be used.”

For example, tanning beds don’t carry as high a tax rate as cigarettes do, Madeleine said. We could also be teaching kids about skin cancer prevention in schools and doing more to combat the pervasive idea among teenagers and young adults that indoor tanning is harmless.

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Good News at Fred Hutch

Solid-tumor faculty retreat fuels immunotherapy and precision-oncology research; Dr. Johnnie Orozco selected to participate in American Society of Hematology faculty-development program

July 2, 2015 | By Fred Hutch staff

Researchers at STTR retreat June 26

Graduate student Chad Toledo, left, talks with Dr. Maciej Mrugala, a Solid Tumor Translational Research faculty member and neuro-oncologist at Seattle Cancer Care Alliance and the University of Washington, during the poster session at last week's STTR retreat.

Photo by Robert Hood / Fred Hutch News Service

Solid-tumor faculty retreat fosters collaboration, fuels immunotherapy and precision-oncology research

On June 26, more than 200 scientists and staff from Fred Hutch, University of Washington and Seattle Cancer Care Alliance gathered in downtown Seattle for the annual Solid Tumor Translational Research retreat. STTR chose “Making Precision Oncology Possible” as the theme for the full-day meeting, which featured a series of presentations highlighting research progress — and prospects — in immunotherapy and precision medicine. 

The common thread across the sessions was identifying opportunities for new collaborations at the interface of these two rapidly evolving fields. 

“There were over 20 projects presented that focused on immunotherapy, genomics, public health and computational oncology, and every presentation ended with a slide on what types of collaboration would get the project to the next level,” said Desert Horse-Grant, STTR’s director of strategy and operations. “This created a buzz of excitement throughout the retreat as people started to see where their expertise could be utilized on projects they were not even aware of.”

The focus on making connections was a natural extension of STTR’s emphasis on helping research teams ask big questions and bring a variety of expertise to bear in search of answers that will shape the future of care for cancer patients. For example, researchers are working toward powerful high-tech, big-data approaches to learn why targeted therapies work well in some patients but not others, who is most likely to benefit from this new generation of treatments, and how to design the next generation of approaches to be even better. 

STTR staff members also announced new resources available to the research community, such as biotools like Oncoscape and HIDRA, which are aimed at accelerating research; and assistance from the STTR administrative team in building road maps for specific funding opportunities. STTR leaders also announced they will soon be offering $1 million in funding over the next three years for three Programmatic Investment Grants — grants made possible by generous private contributions made at the 2014 Hutch Holiday Gala. Information about applying for those grants will be available later this month.

The day was capped off with a keynote speech by Dr. José Baselga, physician-in-chief and chief medical officer at Memorial Sloan Kettering Cancer Center. Baselga shared results from several precision oncology-related initiatives and studies he and his colleagues have implemented, including clinical trials known as basket studies that enroll patients whose cancers originate in different organs but share a common molecular target. 

Horse-Grant was pleased with how well the retreat went. “Our faculty are busy — really busy — but I am so proud that they took the time out of their extraordinarily important clinic and research time to do something new, to get to know our emerging and very powerful solid-tumor community, and to show support to one another,” she said. “This is a wonderful time for our community and a very bad time for cancer as our opponent!”

Dr. Johnnie Orozco

Dr. Johnnie Orozco, a clinical research associate in the lab of Dr. Oliver Press, is using his ASH funding to study a novel approach for the transplantation of blood-forming stem cells.

Fred Hutch file

Dr. Johnnie Orozco selected to participate in American Society of Hematology faculty development program

The American Society of Hematology has announced Dr. Johnnie J. Orozco, a clinical research associate in the Fred Hutch lab of Dr. Oliver Press, as a participant in the 2015 ASH–Harold Amos Medical Faculty Development Program. The program is designed to increase the number of underrepresented-minority scholars in the field of hematology.

“There are a lot of people in this country that feel that diversifying your cadre of researchers is an important goal,” Orozco said. The son of immigrants, Orozco grew up in what he calls “Little Mexico” — Los Angeles — and did not learn English until third grade. “It’s validating to hear that they [the program sponsors] believe in my abilities, my potential and the impact of this work.”

The award, the result of a partnership between ASH and the Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation, grants Orozco four years of support and a total of $420,000 in funding. But “the most valuable part,” Orozco said, is the access to numerous “high-power” program-affiliated mentors across the country. Orozco’s assigned program mentors are Dr. Arturo Molina, an adjunct professor of hematology at City of Hope Comprehensive Cancer Center and a vice president at Johnson & Johnson, and Dr. Griffin Rodgers, the director of the National Institute of Diabetes and Digestive and Kidney Diseases, a branch of the National Institutes of Health.

“Many of the mentors in this program are underrepresented minorities who have also addressed the hurdles often faced by investigators from underrepresented backgrounds and will help me overcome them when I face them, too,” Orozco said. “I feel fortunate to have such a rich source of mentors.”

Through this program, Orozco will study a novel approach for the transplantation of blood-forming stem cells. These transplants are often the only option for a cure for many patients with blood cancers, but current transplantation methods are highly toxic and not 100 percent effective.

Orozco’s research will test the potential of using targeted radioactive molecules — instead of highly toxic full-body irradiation — to prepare the body to receive a stem cell transplant. By targeting radioactive isotopes to the bone marrow only, he hopes to lessen some of the toxicity associated with pre-transplant conditioning.

He will study his targeted radiotherapy in the context of haploidentical, or partially matched, transplantation, in which transplant donor and recipient do not share all of the genetic markers used for matching. Haploidentical transplantation is particularly important for the many people of racial and ethnic minorities who are in need of a transplant but cannot find a fully matched donor among the disproportionately non-Hispanic white donors in transplant registries.

The ultimate goal of this research, Orozco wrote in his application to the program, is to “help define future therapeutic interventions to improve outcomes for patients with cancers of the blood.”

Orozco is one of two 2015 awardees, along with Dr. Jacqueline C. Barrientos of Hofstra North Shore-Long Island Jewish School of Medicine/The Feinstein Institute of Medical Research, who will study Richter’s syndrome.

“By supporting hematologists like Drs. Barrientos and Orozco through the ASH-AMFDP program, ASH aims to develop diverse leaders that will help move hematology forward,” said ASH President David A. Williams in a statement.

Tanning bed use declines, new study shows

Rate of use has dipped slightly but 10 million Americans are still using tanning salons regularly

July 1, 2015 | By Bill Briggs / Fred Hutch News Service

tanning bed

Finally some good news about tanning bed use. The rate declined from dipped slightly from 5.5 percent to 4.2 percent among American adults between 2010 and 2013, a new study shows.

Stock photo by FeaturePics

More Americans are seeing the light when it comes to shunning fake rays to bronze their skin as their rate of tanning-bed use has waned, a federal study reported Wednesday.

The rate of indoor tanning — a habit linked to skin cancers — dipped slightly from 5.5 percent to 4.2 percent among American adults between 2010 and 2013, according to a paper co-authored by a researcher at the Centers for Disease Control and Prevention.

The most promising trend lines emerged in several demographic groups whose indoor-tanning tendencies tumbled during the study years:

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10 years to cancer cures 'actually plausible,' Fred Hutch president says

'We are on the threshold of amazing advances,' Dr. D. Gary Gilliland tells industry, research leaders

June 30, 2015 | By Andrea Detter / Fred Hutch News Service

Dr. D. Gary Gilliland

“Our mantra is Cures Start Here. We’re not looking simply to treat cancer — we’re looking to cure cancer,” Dr. D. Gary Gilliland told hundreds of industry and research leaders at the 2015 Life Science Innovation Northwest conference on Tuesday.

Robert Hood / Fred Hutch News Service

The future of cancer therapy looks “incredibly promising,” Dr. D. Gary Gilliland, president and director of Fred Hutchinson Cancer Research Center, said Tuesday.

“It’s actually plausible that in 10 years we’ll have curative therapies for most if not all human cancers,” Gilliland told hundreds of industry and research leaders from around the world who were gathered in Seattle at the 2015 Life Science Innovation Northwest conference, an event hosted by the Washington Biotechnology & Biomedical Association.

“We are on the threshold of amazing advances in the treatment of cancer,” he said.

Gilliland’s keynote address, and the question-and-answer session that followed, centered on immuno-oncology — or cancer immunotherapy — a family of cancer treatments that harnesses the disease-fighting power of a patient’s own immune system.

“Immuno-oncology is especially exciting for us. This looks to me like a tsunami on the horizon. Cancer can see that tsunami coming … and cancer’s running scared.

“Our mantra is Cures Start Here. We’re not looking simply to treat cancer — we’re looking to cure cancer.”

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