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Matthias Stephan
Matthias Stephan, who studies lymphoma at Seattle’s Fred Hutchinson Cancer Research Center, is among 10 newly named Allen Distinguished Investigators. (Fred Hutch News Service Photo / Robert Hood)

It’s notable that the newest class of Allen Distinguished Investigators, announced today by the Paul G. Allen Frontiers Group, includes researchers who are developing new treatments for lymphoma. Lymphoma is the type of blood cancer that led to the death of Microsoft co-founder Paul Allen, the namesake and funder of the research program.

The decision to focus on that disease — along with nuclear biophysics, neuroimmunology, brain cells and Alzheimer’s disease, and cellular development and aging — was made last year, long before the billionaire philanthropist was diagnosed with a recurrence of his non-Hodgkin’s lymphoma. Nevertheless, the choice is in line with Allen’s willingness to tackle the toughest challenges in bioscience.

The Allen Frontiers Group, a division of the Seattle-based Allen Institute, was created in 2016 with an initial investment of $100 million to fund research that could lead to biomedical breakthroughs.

“Paul’s vision and insight have been an inspiration to me and to many others, both here at the Institute that bears his name and in the myriad of other areas that made up the fantastic universe of his interests. He will be sorely missed,” Allan Jones, president and CEO of the Allen Institute, said in a news release. “We honor his legacy by carrying out our mission of tackling the hard problems in bioscience, as evidenced by these new Allen Distinguished Investigator awards.”

The awards have been given annually starting in 2010, well before the Allen Frontiers Group came into the picture. They’re designed to support early-stage research that’s unlikely to receive support from traditional funding sources but has the potential to produce significant advances in biology.

The researchers in this year’s class brings the total number of Allen Distinguished Investigators to 69. The full roster reads like a who’s who of bioscience, including gene-editing pioneers Jennifer Doudna and Feng Zhang as well as evolutionary geneticists Svante Pääbo and Evan Eichler.

Each of the nine awards given out this year is worth $1.5 million, amounting to a total of $13.5 million. One of the awards is being shared by two researchers, rounding out a class of 10.

Kathy Richmond, director of the Frontiers Group, said Allen “was keenly interested in the work of these 10 exemplary researchers and their potential to push the boundaries of knowledge.”

“Our new investigators all think outside the box to tackle big challenges and find new insights about disease and health,” she said. “Each of them is poised to ‘move the needle’ and drive their fields forward.”

Here’s the full lineup:

Lymphoma

Three awards focus on innovative ideas and technologies that could spur new treatments for lymphoma, a class of blood cancers that sees more than 80,000 new diagnoses in the U.S. alone every year and is linked to the deaths of about 21,000 Americans annually:

  • Matthias Stephan (Fred Hutchinson Cancer Research Center and the University of Washington) will lead the development of a novel nanoparticle immunotherapy for lymphoma. The bioengineered therapy would carry instructions to reprogram a patient’s own immune cells in their body to recognize and destroy lymphoma cells. In this project, Stephan and his colleagues will scale up the nanoparticles to ready them for clinical trials and test their safety in a large animal model.
  • Christian Steidl (BC Cancer Agency and the University of British Columbia) will take a deep dive into classical Hodgkin’s lymphoma by studying the ecosystem of cancer cells and healthy cells that together are known as the tumor microenvironment. Steidl and his team will study lymphoma patients’ biopsy samples before and after cancer relapse, cell by cell.
  • David Weinstock (Dana-Farber Cancer Institute) and Scott Manalis (Massachusetts Institute of Technology) want to convert lymphoma remissions into cures. They aim to tackle the difficult problem of cancer relapse by studying the tiny amounts of lymphoma cells left behind when patients go into remission. By understanding what makes these few straggler cells resistant to treatment, their project could ultimately identify ways to keep lymphoma from coming back.

Nuclear biophysics

Two awards will study how liquids in the nucleus of our cells are organized into different droplets, akin to a microscopic lava lamp. These “phase separations” may influence everything from how the cell makes proteins to how cancer forms:

  • Michael Rosen (University of Texas Southwestern Medical Center) will lead a project studying how liquids behave inside the nucleus. Recent research has found that, much like the separation of oil and vinegar in salad dressing, regions of the nucleus separate into unmixable liquid droplets known as biomolecular condensates. Rosen’s project will probe how these condensates come to be, what they look like in 3-D detail and how defects contribute to a rare type of cancer.
  • Clodagh O’Shea (Salk Institute for Biological Studies) and her team have developed new technologies that reveal how a 6-foot-long stretch of human genomic DNA is compacted into the microscopic cell nucleus. Her team’s hypothesis is that in some regions of the nucleus, molecular chains take a liquid form that allows genes to be read out into their protein products, while in denser regions of the nucleus, those chains turn into gels that keep genes locked away and “silenced.” Liquid-to-gel state transitions may play a role in how cells respond to drugs, cancer-causing genes and viruses.

Neuroimmunology

Two awards support research aimed at exploring the intersections between the brain and the immune system:

  • Chenghua Gu (Harvard Medical School) will study the brain’s elaborate blood vessel system and how it mediates a biochemical dialogue that influences human health and brain disease. The study will focus on the specialized cells that line blood vessels, known as endothelial cells, and how they relay signals between the immune system and the brain.
  • Henrique Veiga-Fernandes (Champalimaud Foundation) has pioneered studies on how the nervous system and the immune system interact throughout our body through his identification of specialized “units” of neuroimmune communication in the gut, lungs, fat and skin. Now, he and his research team will develop new techniques to measure how neurons and immune cells interact and influence each other throughout the body.

Astrocytes and Alzheimer’s

One award looks at astrocytes, a type of brain cell that may play an important role in Alzheimer’s disease.:

  • Baljit Khakh (UCLA) and his team will tackle the first systematic characterization of astrocytes, study how these cells influence neuron activity, and explore how astrocyte function is altered in a mouse model of Alzheimer’s disease. Khakh’s study could uncover new therapeutic targets for this devastating neurological disorder.

Development and aging

One award delves into the potential links between embryonic development and aging.:

  • Marc Kirschner (Harvard Medical School) and his colleagues are taking a big-picture approach to understanding the biology of early development and of aging, two processes that bookend the lives of all living creatures. Kirschner aims to use systems biology and machine learning approaches to uncover the cellular circuitry that drives each process, and to better understand where they might overlap. The experimental model for this project will be the small crustacean Daphnia magna, also known as the water flea.
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