The 2017 fellows are:

, professor and chair of microbiology, was chosen for his seminal work on topological problems in DNA replication, repair and related activities. His research helps explain how the DNA double helix overcomes mechanical obstacles posed by its twisted structure. Resembling a wound-up rope-ladder, DNA becomes entangled when its rungs split to allow itself to replicate. Champoux studied an enzyme called DNA topoisomerase that provides swivels to remove these tangles. His lab has explored many other structural and mechanical aspects of nucleic acid structure and synthesis, such as DNA coiling and relaxation. In addition, Champoux researches replication in retroviruses, and the effects of anticancer drugs on the DNA topoisomerase. This is his 45^th year as a UW School of Medicine faculty member.

, professor of both pediatrics and laboratory medicine, was selected for her distinguished research on HIV infections in newborns, children and adults. She is noted for her U.S. and global health efforts to prevent transmission of HIV from mothers to their infants, particularly in places lacking adequate healthcare and economic resources. Her research encompasses: why HIV infections persist despite effective antiviral therapy; why people treated for HIV continue to have higher cancer rates; and how drug-resistant HIV becomes established in children and adults. Frenkel is collaborating with bioengineers on a quick, affordable test for detecting HIV drug resistance. She practices at the Pediatric Infectious Diseases Virology Clinic at and co-directs the Seattle Children’s Center for Global Infectious Diseases.

, professor and chair of physiology & biophysics, was recognized for his distinguished work on the molecular mechanisms of muscular dystrophies, a category of diseases that cause muscle wasting. His hope is to repurpose existing drugs and find new drugs to slow muscle degeneration and heart failure in Duchenne muscular dystrophy as well as other muscle diseases. His lab studies the structure and signaling activity of the dystrophin complex, which is important in skeletal muscle and the heart.  In 1987 his team discovered the syntrophins, a family of proteins that associate with dystrophin and recruit signaling proteins, channels, transporters and receptors to the cell membrane. These proteins also play important roles at the junction between nerve cells and muscle fibers and at the blood-brain barrier. Froehner’s investigation of the dystrophin complex is also relevant to other medical conditions, including stroke, brain swelling, epilepsy, and heart and blood vessel disorders.

, professor of medicine and a investigator, was chosen for elucidating some of the molecular features of the evolutionary arms race between cytomegalovirus and its human hosts. Most people who carry cytomegalovirus have no symptoms. However, for newborns, transplant recipients, AIDS patients and others with weak immune systems, the virus can cause health problems. Geballe’s lab has discovered genes on the human cytomegalovirus that can block the body’s antiviral response. Geballe is a physician at the , where he specializes in treating infectious diseases.

, professor of medicine and genome sciences, and head of the Division of Medical Genetics, was selected for her contributions to the field of human genetics. She was recognized for work on the genetics of common, complex diseases, including cancer, dementia, stroke and immune disorders. She is a collaborator in the (Electronic Medical Records and Genomics) network.  This consortium combines DNA biorepositories with data from clinical records to conduct large-scale genomic studies for a variety of conditions. Jarvik also studies the implementation of genomic medicine in clinical practice. She is a physician at the UW Medicine Genomics Clinic.

, professor of pathology, is noted for his contributions to the understanding of the molecular and cellular mechanisms of aging and longevity. He studies how some mechanisms were conserved during evolution across species, from yeast and worms and to mice and humans. He has looked at several factors proposed to slow down aging, such as caloric restriction and the drug rapamycin. His lab focuses on developing therapies to delay the onset of age-related diseases in people by targeting biological pathways associated with aging. In other endeavors, his Dog Aging Project is looking to extend the active lifespan of pets. Kaeberlein was the founding director of the at the UW.  He also has served as co-director of the UW’s .

, professor of mechanical engineering, was honored for contributions in fluid mechanics. His research focuses on modeling and numerical simulation of various transitioning and turbulent flows, which play an important role in many natural and technological processes ranging from the fate of ozone in the atmosphere, to the properties of gas turbine engines, to the efficient and clean use of energy. Riley has made advancements in the understanding of turbulent, multi-phase flows; turbulent density-stratified flows; turbulent shear flows and turbulent reacting flows. He teaches courses in fluid mechanics at both the undergraduate and graduate levels, and is an adjunct professor in applied mathematics and in aeronautics and astronautics. Riley is also a member the National Academy of Engineering and of the Washington State Academy of Sciences, and is a fellow of both the American Physical Society and American Society of Mechanical Engineers, among other honors. He has been at the UW since 1983 and holds the PACCAR Professorship in Engineering.

, an affiliate professor of aquatic and fishery sciences, chemistry and law, was elected for her contributions to environmental chemistry and toxicology. She is particularly noted for establishing and communicating the impact of environmental contaminants — especially hydrocarbons — on marine organisms and ecosystems. Her research on how marine organisms process contaminants led to the development of techniques used by NOAA to inform the impacts of oil-related pollution on fisheries resources and ensure that seafood is safe for human consumption. Based on their widely recognized expertise in oil spill detection and rapid analysis, Varanasi and her team were at the forefront of the agency’s seafood safety response after environmental catastrophes, including the Exxon Valdez oil spill, the Persian Gulf War and Hurricane Katrina. Varanasi retired at the end of 2010 as the science and research director of NOAA’s , a position she held since 1994 when she became the first woman to lead a fisheries field office. A UW doctoral alumna, Varanasi is now a Distinguished Scholar in Residence with the UW’s College of the Environment and the Center for Urban Waters.

, a senior scientist at NOAA/Pacific Marine Environmental Laboratory and an affiliate professor of oceanography at the UW, was also named a AAAS fellow this year for leading research efforts on ocean acidification and shifting public policy to address the growing environmental issue.

The transplant anti-rejection drug rapamycin showed unexpected benefits in a mouse model of a fatal defect in the energy powerhouses of cells, the mitochondria. Children with the condition, Leigh syndrome, show progressive brain damage, muscle weakness, lack of coordination or muscle control, and weight loss, and usually succumb to respiratory failure.

Leigh syndrome is often diagnosed within the first year of life. Affected children rarely survive beyond 6 or 7 years. At present, the disorder, which can result from several different underlying causes, has no effective treatment.

Reporting this week in , UW researchers said that they found that treatment with rapamycin “robustly enhances survival and attenuates disease progression in a mouse model of Leigh’s syndrome.” Given as a daily injection, the drug delayed the onset of neurological symptoms, reduced brain inflammation, and prevented brain lesions.

For most of their lives, the treated mice breathed normally, and did not clasp their legs against their bodies, a posture characteristic of this and related brain disorders in mice. Unlike the untreated mice, they could balance and run on a rotarod, a miniature log rolling exercise toy. Both the median and maximum lifespans within the group of treated mice were strikingly extended, the authors noted.

The median lifespan for this mouse condition is 50 days. In comparison, treated males lived a median of 114 days, and females 111 days. The longest survival in the treated group was 269 days, more than triple that of the untreated animals.

“We were excited at the findings because of the potential impact on treatment for kids with this or related mitochondrial diseases,” said the senior author of the study, Dr. Matt Kaeberlein, UW associate professor of pathology. “Similar intervention strategies might also prove useful for a broad range of mitochondrial diseases or for other conditions resulting from mitochondrial dysfunction.”

Mitochondrial defects lessen the amount of energy available to cells. The depletion can damage or destroy vital tissues. Symptoms and severity of illness depends on which types of cells are affected, but in many cases several organ systems operate poorly as a consequence of malfunctioning mitochondria.

Beyond specific mitochondrial diseases, most of them genetic in origin, the decline or dysfunction of mitochondria contribute to many common health problems, including some forms of heart disease, cancer, and muscle, nerve or brain degeneration associated with aging.

Kaeberlein, who researches factors that lengthen life, has been studying the anti-aging effects of rapamycin for several years. The drug, like calorie-restricting diets, acts by inhibiting mTOR, an abbreviation for the eponymously named mechanistic target of rapamycin.

Kaeberlein said, “This study suggests that this drug’s inhibition of mTOR may have a major impact on mitochondria and energy production in cells. We know that rapamycin appears to slow aging. What we don’t know is whether the effects of rapamycin on mitochondria are a major part of the effects of rapamycin on normal aging and aging-related diseases.”

Alongside their work in aging and lifespan in normal mice, Kaeberlein and his lab decided to study rapamycin’s actions on mice with a severe mitochondrial defect. The mouse model for Leigh syndrome was created in the UW laboratory of Dr. Richard Palmiter, a professor of biochemistry and Howard Hughes Medical Institute investigator who was one of the early originators of transgenic mouse models.

The research team included Dr. Philip G. Morgan and Dr. Margaret M. Sedensky, from the Department of Anesthesiology and Pain Medicine at Seattle Children’s Hospital, who study mitochondrial diseases in patients. The lead scientist was Simon C. Johnson from the UW Department of Pathology.

After seeing unexpected benefits on health and survival, the research group looked closely at the effects on metabolism by examining the levels of more than 100 different metabolites – cellular building blocks and intermediates used to make energy – in the treated and untreated Leigh syndrome mice. The team observed that treated mice appear to burn more amino acids and fats as an energy source, rather than the sugar, glucose. This eliminated the accumulation of glucose breakdown byproducts, including lactate. These byproducts can be toxic and are seen at high levels in human Leigh syndrome patients.

“The drug did not substantially alter mitochondrial composition. Instead, the mice appear to bypass the deficiency in their mitochondria through a shift in their metabolic pattern,” Kaeberlein said. “However, we can’t yet explain exactly how this rescues the mice with Leigh syndrome.”

Because this was a mouse study, evidence of efficacy of rapamycin in Leigh syndrome patients will be a necessary next step. Rapamycin already has FDA approval for several uses, including preventing organ transplant rejection and for treating rare forms of cancer; however, the drug also has side-effects which might limit its utility in very young children. Kaeberlein is optimistic, however, that “even if rapamycin doesn’t turn out to be be useful as a treatment for Leigh Syndrome, the lessons learned here will pave the way to new therapies for this devastating disease.”

In addition to Kaeberlein, Palmiter, Morgan, Sedensky and Johnson, the researchers on the study were Melana E. Yanos, Ernst-Bernhard Kayser, Albert Quintana, Maya Sangesland, Anthony Castanza, Lauren Uhde, Jessica Hui, Valerie Z. Wall, Arni Gagnidze, Kelly Oh, Brian M. Wasko, Fresnida J. Ramos, and Peter S. Rabinovitch.

The study was funded by the UW School of Medicine and the UW Department of Pathology through the Healthy Aging and Longevity Research Institute. Some of the researchers were supported by NIH training grants T32AG000057 and T32ES007032, and an Amgen Scholar grant.