Don W. Cleveland Awarded 2018 Breakthrough Prize


On December 3, 2017, Don W. Cleveland, PhD, Distinguished Professor of Cellular and Molecular Medicine, Neurosciences and Medicine and chair of the Department of Cellular and Molecular Medicine, was honored with the Breakthrough Prize in Life Sciences for his work, "elucidating the molecular pathogenesis of a type of inherited ALS, including the role of glia in neurodegeneration, and for establishing antisense oligonucleotide therapy in animal models of ALS and Huntington’s disease.”

Dr. Cleveland has made seminal contributions to the understanding of how brain cells grow during normal mammalian development and how defects in those mechanisms lead to inherited neurodegenerative diseases, such as ALS and Huntington’s. Breaking with the mainstream belief in the field, Cleveland discovered that the genetic mutations that cause these diseases affect not just neurons, but the entire neighborhood of brain cells. He was the first to purify tau, the protein that mis-assembles and accumulates in Alzheimer’s disease and chronic brain injury, where it correlates with cognitive decline.

Based on these fundamental findings, Cleveland and his colleagues developed a ground-breaking approach to treating neurodegenerative diseases: designer DNA drugs that reduce synthesis of the toxic proteins produced by gene mutations or increase production from poorly expressed genes. This technology has already proven successful — it’s the underlying principle behind Ionis Pharmaceuticals’ FDA-approved therapeutic for spinal muscular atrophy, an inherited muscle wasting condition that was previously always fatal. Now, kids who were completely immobilized are walking. Similar designer DNA drugs are currently in clinical trials for the treatment of ALS, Huntington’s disease and Alzheimer’s disease.

Marilyn G. Farquhar Receives 2017 Revelle Medal


On November 17, 2017, Marilyn G. Farquhar, PhD, distinguished professor emerita of cellular and molecular medicine, was awarded the 2017 UC San Diego Revelle Medal, the highest honor bestowed by the Chancellor to current and former faculty members to recognize sustained, distinguished, and extraordinary service to the UCSD community, as well as a record of accomplishment that advances the UC San Diego mission of exceptional teaching, research, service and patient care.

Dr. Farquhar entered the field of science when female graduate students were rare. Today, her discoveries are part of the canon of cell biology. She joined UC San Diego in 1990 and served as the school’s first chair of the Department of Cellular and Molecular Medicine. She helped build the UC San Diego School of Medicine to become a top-ranked, national program. Farquhar is a founding member and former president of The American Society for Cell Biology. Her dedication to teaching and mentorship has made a powerful impact on the physicians and medical scientists of tomorrow.

After stints at the University of California, San Francisco, The Rockefeller University—where she became the first woman to be named a professor of cell biology—and Yale University, Farquhar joined UC San Diego in 1990, with her husband, famed physician-scientist George Palade. Farquhar served as the school’s first chair of the Department of Cellular and Molecular Medicine. She helped build the UC San Diego School of Medicine to become the top-ranked program it is today—the nation’s 18th best research-intensive medical school, according to U.S. News World Report.

Farquhar’s research accomplishments have been recognized by many prestigious awards including the E.B. Wilson Medal of the American Society of Cell Biology, the Distinguished Scientist Medal of the Electron Microscopy Society of America, the Homer Smith Award of the American Society of Nephrology and the Rous-Whipple Award of the American Society for Investigative Pathology. She is also well known for her dedication to teaching and mentorship, making a great impact in training the next generation of outstanding physicians and medical scientists.


Repurposed Drug Found to be Effective against Zika Virus
In both cell cultures and mouse models, a drug used to treat Hepatitis C effectively protected and rescued neural cells infected by the Zika virus — and blocked transmission of the virus to mouse fetuses.

Writing in the current online issue of the journal Scientific Reports , researchers at University of California San Diego School of Medicine, with colleagues in Brazil and elsewhere, say their findings support further investigation of using the repurposed drug as a potential treatment for Zika-infected adults, including pregnant women.

“There has been a lot of work done in the past year or so to address the Zika health threat. Much of it has focused on developing a vaccine, with promising early results,” said senior author Alysson Muotri, PhD, professor in the UC San Diego School of Medicine departments of Pediatrics and Cellular and Molecular Medicine, director of the UC San Diego Stem Cell Program and a member of the Sanford Consortium for Regenerative Medicine.
Lab-grown neurons showcase effects of autism mutations
Neurons derived from people with mutations linked to autism display diverse abnormalities that may help explain the origins of these individuals’ features, according to three new studies.

In all three studies, researchers reprogrammed skin cells from individuals with one of these mutations into stem cells that can mature into any cell type. They then turned these induced pluripotent stem (iPS) cells into neurons.

The studies also illustrate the promise of the iPS cell approach for understanding how genetic mutations lead to functional impairments, says Alysson Muotri, PhD, professor of pediatrics and of cellular and molecular medicine at the University of California, San Diego, who was not involved in the study. “This is a nice representation of the type of work that’s possible,” he says.
Anti-Malaria Drug May Help Prevent Zika Infections
Researchers at UC San Diego School of Medicine and Sanford Burnham Prebys Medical Discovery Institute report that a medication long used to prevent and treat malaria may also be effective against Zika.

The medication is chloroquine, discovered in 1934 and used worldwide, particularly in developing countries where malaria is endemic, to prevent or treat the infectious disease.

Researchers studied pregnant mice infected with the Zika virus, treating them with chloroquine (delivered through drinking water) at doses equivalent to acceptable levels used in humans.

“Our research is the first to study Zika infection in a mouse model that transmits the virus in a way similar to humans,” said Alysson R. Muotri, PhD, professor and director of the Stem Cell Program at UC San Diego and co-senior author of the study with Alexey Terskikh at Sanford Burnham Prebys.
Designer DNA drugs approach a potential watershed moment
Next year, Carlsbad’s Ionis Pharmaceuticals is expected to release clinical trial results for Huntington’s and Lou Gehrig’s diseases that use designer DNA drugs to mute the mutant genes responsible for causing patients’ nervous systems to gradually go haywire.

Ionis has been able to previously show success working on the far side of the blood-brain barrier, a protective shield of sorts that automatically filters out most drugs injected into the bloodstream, making targets in the brain and spine extremely difficult to hit, with an FDA approved drug called 'Spinraza'.

If early-phase results, the first of which are expected in January, show that these DNA drugs — formally called “antisense oligonucleotides” — can reduce harmful proteins in nerve cells, it will be a watershed moment toward creating viable long-term treatments.

“We don’t get two hours of efficacy. We don’t get two to three days. We don’t get two or three weeks. We get three or four months. The drug lasts a really long time,” Don Cleveland, PhD, said.

That means that patients could theoretically come in a few times a year, get a shot in the spine, and go home.

“That would be more like going to the dentist. You don’t necessarily look forward to it, but you do it,” Cleveland said.
Frozen in Action: How Cells Repair DNA as it's Being Transcribed
In a paper published November 22 in Nature, Dong Wang, PhD, Andres Leschziner, PhD, and colleagues used cryoEM to get a clear look at how cells repair damaged bits of DNA that hold up the molecular machinery trying to transcribe it into mRNA. This process is called transcription-coupled repair.

Wang and Leschziner’s team solved the first cryoEM structure of the yeast form of the key proteins that initiate transcription-coupled repair, known as the Pol II-CSB complex.

“Our work with the Wang lab is a beautiful example of how structure tells us about function,” said Leschziner, professor in the UC San Diego School of Medicine and division of biological sciences.
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