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Capturing information from thousands of cells at once

New technology allows scientists to peek inside nearly 70,000 cells at once

Jan. 16, 2017 | By Sabrina Richards / Fred Hutch News Service

Dr. Jason Bielas

Dr. Jason Bielas

Robert Hood / Fred Hutch News Service

Researchers have developed a new technique that allows them to examine huge amounts of information from a single cell or zoom out and see data patterns among thousands upon thousands of cells — all in a single experiment. In work published Monday in the journal Nature Communications, scientists from the biotech company 10x genomics and Fred Hutchinson Cancer Research Center describe their method, which could help researchers dive deep into the ecosystem of cancer or other diseases.

The platform allows researchers to analyze which genes are turned on (and to what level) in tens of thousands of cells at once.

“What the technology allows you to do is to be able to identify different types of cells and how many there are, and also infer what they’re doing based on gene expression,” which could give researchers a better understanding of diseases such as leukemia, noted co-author Dr. Jerald Radich, a Fred Hutch physician-scientist who specializes in leukemia research.

Radich is working with the new technology to gain a better understanding of which cell types contribute to leukemia relapse. Once that’s understood, “you can imagine using it in the clinic as an adjunct to the ways that we look at residual disease [low levels of remaining leukemia cells that can contribute to relapse],” he said.

Fred Hutch’s Dr. Jason Bielas, the paper’s lead author, developed methods and designed the experiments needed to validate the platform, known as the Chromium Single Cell 3’ Solution. He and his team were able to analyze nearly 70,000 cells in a single experiment and use gene expression patterns to group individual cells by type.

Bielas also developed additional methods to detect subtle DNA variations and further expand the technology’s applications. Current methods to detect leukemic cells in patients often rely on surface markers. Using only gene expression information and slight differences in gene sequences, the team was able to distinguish between donor and recipient blood cells in patients who had received bone marrow transplants to treat their leukemia — an important component of patient care after transplant.

“We developed methods that we believe can be used to improve clinical care of cancer patients and save lives, in addition to addressing fundamental questions in biology,” said Bielas, who studies how errors in the genetic code contribute to disease and develops new technologies to address long-standing questions in mutation research.

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Good News at Fred Hutch

Celebrating faculty and staff achievements

Jan. 12, 2017

Dr. Rajesh Uthamanthil

Dr. Rajesh Uthamanthil with the book he co-authored, the authoritative text on tumor avatar models.

Photo by Robert Hood / Fred Hutch News Service

Dr. Rajesh Uthamanthil co-authors tumor ‘avatar model’ book

Fred Hutch’s Dr. Rajesh Uthamanthil has recently written a book on tumor avatar models — or make that, the book on tumor avatar models. Also known as “patient-derived xenografts,” or PDX, these mouse models aim to recapitulate tumors’ complexity and individuality more fully than previous preclinical models — cell lines grown from a single type of cancerous cell but passaged multiple times in petri dishes, and mouse models of cancer derived from these cell lines.

As director of the Fred Hutch Comparative Medicine Program, Uthamanthil’s singular focus is making better preclinical models for translational work, he said. As part of that effort, he’s currently leading the Hutch’s PDX Core Program, which is less than a year old and now houses avatar mice that bear tumors taken from patients with many different types of cancer. Recently, Uthamanthil also became interim leader of Fred Hutch's Shared Resources department and said he hopes to channel his passion into leading research resources that provide outstanding services to support science at Hutch.

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New library of HIV mutants could inform vaccine design

Laboratory manipulation of the AIDS-causing virus reveals evolutionary ‘dead-ends’

Jan. 12, 2017 | By Rachel Tompa / Fred Hutch News Service

HIV

There’s a small collection of test tubes stored in a laboratory freezer at Fred Hutchinson Cancer Research Center. Hundreds of these freezers host thousands of tiny tubes, but this collection is different.

This one houses a multitude of possibilities.

In each tube, suspended in a few drops of water, is a collection of millions of mutant HIV viruses. Some of these mutants are very good at infecting human cells, no different from their “natural” viral ancestor. Some of them are worse.

Together, they can teach researchers something important about HIV in humans, say the collection’s creators, Fred Hutch evolutionary biologists Hugh Haddox and Dr. Jesse Bloom.

In a study published online last month in the journal PLOS Pathogens, the researchers describe their library of mutant HIVs, its creation, and how they used it to show that a certain type of HIV vaccine, designed to elicit the immune molecules known as broadly neutralizing antibodies, could be on the right track.

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Clearing up another mammogram muddle

Confused about the latest breast-cancer screening study? Fred Hutch, SCCA experts have answers

Jan. 11, 2017 | By Diane Mapes / Fred Hutch News Service

Woman looking at mammography screen

A new study out of Denmark has raised questions and concerns about the prevalence of overtreatment in breast cancer patients diagnosed after mammogram. Our experts clear things up.

File photo by Rui Vieira / AP

Barbara Barrett is confused.

The 58-year-old retired teacher and elementary school counselor, who lives outside of Spokane, Washington, is due for a mammogram. But Tuesday’s headlines about mammograms leading to overtreatment in a “third of breast cancer patients” have given her — and thousands of other women across the country — huge cause for concern. 

Yet again.

“I have increased anxiety about what I would do if something were found during my mammogram,” she said. “And I’m definitely confused reading the new info. Is there a way to know whether a tumor found in a mammogram should be treated or left alone?”

The headlines are based on a Danish study and an accompanying commentary by the chief medical officer of the American Cancer Society published Monday in the Annals of Internal Medicine.  Both the study and commentary point to one of mammography’s biggest flaws: Along with picking up aggressive cancers that can go on to kill, they can also pick up slow-growing tumors that may never amount to anything. These “early cancers” include DCIS (ductal carcinoma in situ) or stage 0 breast cancers that are sometimes, but not always, harmless. 

Unfortunately, we’re not quite yet able to consistently differentiate between the early-stage cancers that kill and the cancers that simply creep along (not to mention creep you out). So some women diagnosed with breast cancer may get, say, a mastectomy rather than a lumpectomy. Or get a lumpectomy and radiation for their DCIS when hormonal therapy alone might suffice. Some may even get chemotherapy that they don’t really need because a mammogram has only pointed to cancer — not a crystal clear vision of what the future holds.

Early cancers don’t always advertise their intent. They’re merely diagnosed and treated and sometimes, yes, overtreated. And that’s a huge concern — for cancer patients, for researchers and oncologists and, perhaps most of all, for women like Barbara Barrett who are trying to make health decisions while being inundated by headlines like: “Third of breast cancer patients treated unnecessarily, study says,” and “Time to rethink mammograms, American Cancer Society top doc says.”

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A Q&A with Fred Hutch postdoctoral research fellow Dr. Rachel Perret

As part of a world-class immunotherapy research team, Perret is working her ‘dream job’ — trying to bring T-cell therapy to all who need it

Jan. 9, 2017 | By Rachel Tompa / Fred Hutch News Service

Fred Hutch immunotherapy researcher Dr. Rachel Perret

Fred Hutch file

Not many people would describe the best part of their job as the time they had to pull several near all-nighters in a single week.

But not many people get to work on their passion — uncovering the inner workings of the human body while simultaneously developing a technology that could help thousands of people diagnosed with cancer — as a day job.

Fred Hutchinson Cancer Research Center’s Dr. Rachel Perret is one of those lucky few. A postdoctoral research fellow training under the mentorship of immunotherapy expert Dr. Phil Greenberg, Perret spends her days — and sometimes her nights — working toward an “off-the-shelf” version of T-cell therapy.

The type of T-cell therapy Greenberg’s team is developing involves genetically engineering patients’ own immune cells to carry more potent versions of natural immune molecules, known as T-cell receptors, that recognize proteins made by cancer cells but not healthy cells. Such engineered T cells are then transferred back into cancer patients where they are able to better recognize and destroy patients’ tumors. Perret’s broader approach to the already-lifesaving technique could, one day, provide a matched immunotherapy for close to 90 percent of patients with acute myeloid leukemia. Today, nearly 20,000 cases of AML are diagnosed every year in the U.S. and more than 10,000 people die of the disease. Perret’s work could someday apply to other cancer types as well, including lung, ovarian and pancreatic cancers.

Recently, the native New Zealander took a break from her busy research schedule to describe what, exactly, she studies, as well as how she decided to become a scientist and why late nights in the lab are so inspiring. 

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'We've become full partners'

An HIV laboratory in South Africa advances scientific understanding, and more

Jan. 6, 2017 | By Mary Engel / Fred Hutch News Service

Dr. Erica Andersen-Nissen Cape Town HVTN Immunology Laboratory

Fred Hutch's Dr. Erica Andersen-Nissen and her family moved to Cape Town four years ago to set up a state-of-the-art laboratory for the HIV Vaccine Trials Network.

Robert Hood / Fred Hutch News Service

When Fred Hutchinson Cancer Research Center immunologist Dr. Erica Andersen-Nissen moved to Cape Town, South Africa, in 2013 her goal was to set up a state-of-the-art laboratory for the Fred Hutch-based HIV Vaccine Trials Network in time to anchor two groundbreaking clinical trials.

Both trials launched last year, and the lab and its 15 researchers, technicians and data manager were ready. The lab has begun analyzing the first of tens of thousands of blood and tissue samples to study trial participants’ immune reactions over the next four years.

As if opening one of the most advanced laboratories in Africa to work on two major clinical trials at the same time weren’t ambitious enough, Andersen-Nissen also is on her way to fulfilling the lab’s long-term mission: Working with local researchers to build scientific capacity in South Africa and its neighboring countries that will extend beyond the work of the HVTN.

“There’s a long history of doing clinical trials in developing countries and taking the specimens out of the country,” Andersen-Nissen said in an interview in her Cape Town office. “Then the people who participate in these trials have no stake in the intellectual property and in the advances that are being made. There’s a growing cadre of top quality researchers in South Africa who should be studying specimens from their own population.”

Twelve of the 14 people Andersen-Nissen has hired are South African, and two others are from neighboring countries.

This is a story of building that lab, from the people up.

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