LA JOLLA—Pancreatic cancer is one of the deadliest cancers—only about one in eight patients survives five years after diagnosis. Those dismal statistics are in part due to the thick, nearly impenetrable wall of fibrosis, or scar tissue, that surrounds most pancreatic tumors and makes it hard for drugs to access and destroy the cancer cells.
LA JOLLA—Regulatory T cells are specialized immune cells that suppress the immune response and prevent the body from attacking its own cells. Understanding how these cells work is key to determining how they might be manipulated to encourage the destruction of cancer cells or prevent autoimmunity. Cell behavior is influenced by chromatin architecture (the 3D shape of chromosomes) and which genes are accessible to proteins—like Foxp3, which promotes regulatory T cell development.
LA JOLLA—Salk Institute researchers, as part of a larger collaboration with research teams around the world, analyzed more than half a million brain cells from three human brains to assemble an atlas of hundreds of cell types that make up a human brain in unprecedented detail.
LA JOLLA—Pancreatic cancers are among the most aggressive, deadly tumor types and, for years, researchers have struggled to develop effective drugs against the tumors. Now, Salk researchers have identified a new set of molecules that fuel the growth of tumors in pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer.
LA JOLLA—Salk Institute researchers, in collaboration with the National Institutes of Health, have discovered the molecular mechanisms by which the human immunodeficiency virus (HIV) becomes resistant to Dolutegravir, one of the most effective, clinically used antiviral drugs for treating HIV.
LA JOLLA—The immune system protects the body from invaders, such as bacteria, viruses, or tumors, with its intricate network of proteins, cells, and organs. Specialized immune cells, called cytotoxic T cells, can develop into short-lived effector cells that kill infected or cancerous cells within our bodies. A small portion of those effector cells remain after an infection and become longer-lived memory cells, which “remember” infections and respond when infections reappear. But little was known about what influences cytotoxic T cells to transform into these effector and memory T cell subtypes.
LA JOLLA—The cellular life inside a plant is as vibrant as the blossom. In each plant tissue—from root tip to leaf tip—there are hundreds of cell types that relay information about functional needs and environmental changes. Now, a new technology developed by Salk scientists can capture this internal plant world at an unprecedented resolution, opening the door for understanding how plants respond to a changing climate and leading to more resilient crops.
LA JOLLA—The Salk Institute and Autobahn Labs, an early-stage drug discovery incubator, will work together to identify and advance promising initial scientific discoveries through the preliminary steps of drug discovery and development. Autobahn Labs will invest up to $5 million per project for Salk discoveries that require access to drug development expertise and state-of-the art capabilities.
LA JOLLA—Five Salk Institute faculty members have been promoted for their notable, innovative contributions to science. These faculty members have demonstrated leadership in their disciplines, pushing the boundaries of basic scientific research. Assistant Professors Sung Han, Dmitry Lyumkis, and Graham McVicker were promoted to associate professors, and Associate Professors Sreekanth Chalasani and Ye Zheng were promoted to professors. The promotions were based on Salk faculty and nonresident fellow recommendations and approved by Salk’s president and Board of Trustees on April 21, 2023.
LA JOLLA—Scientists often act as detectives, piecing together clues that alone may seem meaningless but together crack the case. Professor Reuben Shaw has spent nearly two decades piecing together such clues to understand the cellular response to metabolic stress, which occurs when cellular energy levels dip. Whether energy levels fall because the cell’s powerhouses (mitochondria) are failing or due to a lack of necessary energy-making supplies, the response is the same: get rid of the damaged mitochondria and create new ones.
LA JOLLA—Itch is a protective signal that animals use to prevent parasites from introducing potentially hazardous pathogens into the body. If a mosquito lands on a person’s arm, they sense its presence on their skin and quickly scratch the spot to remove it. Itchiness due to something like a crawling insect is known as “mechanical” and is distinct from “chemical” itchiness generated by an irritant such as the mosquito’s saliva if it were to bite the person’s arm. While both scenarios cause the same response (scratching), recent research by Salk Institute scientists has revealed that, in mice, a dedicated brain pathway drives the mechanical sensation and is distinct from the neural pathway that encodes the chemical sensation.
LA JOLLA—Cancer treatments have long been moving toward personalization—finding the right drugs that work for a patient’s unique tumor, based on specific genetic and molecular patterns. Many of these targeted therapies are highly effective, but aren’t available for all cancers, including non-small cell lung cancers (NSCLCs) that have an LKB1 genetic mutation. A new study led by Salk Institute Professor Reuben Shaw and former postdoctoral fellow Lillian Eichner, now an assistant professor at Northwestern University, revealed FDA-approved trametinib and entinostat (which is currently in clinical trials) can be given in tandem to produce fewer and smaller tumors in mice with LKB1-mutated NSCLC.
LA JOLLA—Numerous studies have shown health benefits of time-restricted eating including increase in life span in laboratory studies, making practices like intermittent fasting a hot topic in the wellness industry. However, exactly how it affects the body on the molecular level, and how those changes interact across multiple organ systems, has not been well understood. Now, Salk scientists show in mice how time-restricted eating influences gene expression across more than 22 regions of the body and brain. Gene expression is the process through which genes are activated and respond to their environment by creating proteins.
LA JOLLA—Cancer, caused by abnormal overgrowth of cells, is the second-leading cause of death in the world. Researchers from the Salk Institute have zeroed in on specific mechanisms that activate oncogenes, which are altered genes that can cause normal cells to become cancer cells.
LA JOLLA—The San Diego Nathan Shock Center of Excellence in the Basic Biology of Aging, a collaboration between the Salk Institute, UC San Diego, and Sanford Burnham Prebys, received new funding from the National Institutes of Health (NIH) to enroll participants from the Rancho Bernardo Study of Healthy Aging into their own clinical cohort to study differences in how individuals age. Initiated 50 years ago by the late UC San Diego Distinguished Professor Elizabeth Barrett-Connor, the Rancho Bernardo Study is one of the longest, continuously NIH-funded studies in existence.
LA JOLLA—With a five-year, $126 million grant from the National Institutes of Health (NIH), a team led by Salk Institute scientists has launched a new Center for Multiomic Human Brain Cell Atlas. Part of the NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, the project aims to describe the cells that make up the human brain in unprecedented molecular detail, classify brain cells into more precise subtypes, and pinpoint the location of each cell in the brain. What’s more, the team will track how these features change from early to late life.
LA JOLLA—A stretch of DNA that hops around the human genome plays a role in premature aging disorders, scientists at the Salk Institute and King Abdullah University of Science and Technology (KAUST) in Saudi Arabia have discovered. In people with early aging, or progeria, RNA encoded by this mobile DNA builds up inside cells. What’s more, the scientists found that blocking this RNA reverses the disease in mice.
LA JOLLA—Scientists from the Salk Institute and the University of Sheffield co-led a study that shows promise for the development of gene therapies to repair hearing loss. In developed countries, roughly 80 percent of deafness cases that occur before a child learns to speak are due to genetic factors. One of these genetic components leads to the absence of the protein EPS8, which coincides with improper development of sensory hair cells in the inner ear. These cells normally have long hair-like structures, called stereocilia, that transduce sound into electrical signals that can be perceived by the brain. In the absence of EPS8, the stereocilia are too short to function, leading to deafness.
LA JOLLA— Mitochondria are known as cells’ powerhouses, but mounting evidence suggests they also play a role in inflammation. Scientists from the Salk Institute and UC San Diego published new findings in Immunity on August 2, 2022, where they examined human blood cells and discovered a surprising link between mitochondria, inflammation and DNMT3A and TET2—two genes that normally help regulate blood cell growth but, when mutated, are associated with an increased risk of atherosclerosis.
LA JOLLA—Researchers at the Salk Institute and King Abdullah University of Science and Technology (KAUST) in Saudi Arabia have discovered a new underlying cause of Wiskott-Aldrich syndrome, a rare genetic disease that leads to bleeding and immune deficiencies in babies. Their findings, published in the journal Nature Communications on June 25, 2022, revolve around how cells cut and paste strands of RNA in a process called RNA splicing. The genetic mutations associated with Wiskott-Aldrich syndrome, they found, disrupt this process which, in turn, prevents numerous immune and anti-inflammatory proteins from being made correctly.
LA JOLLA–Insect-eating plants have fascinated biologists for more than a century, but how plants evolved the ability to capture and consume live prey has largely remained a mystery. Now, Salk scientists, along with collaborators from Washington University in St. Louis, have investigated the molecular basis of plant carnivory and found evidence that it evolved from mechanisms plants use to defend themselves.
LA JOLLA—The Salk Institute has named plant molecular geneticist Mary Lou Guerinot a Nonresident Fellow, a group of eminent scientific advisors that guide the Institute’s leadership. Guerinot holds the Ronald and Deborah Harris Professorship in the Sciences and is a professor of biological sciences at Dartmouth College, where she was the first woman to chair a science department.
LA JOLLA—The Salk Institute has named Gerald Joyce, a professor in the Jack H. Skirball Center for Chemical Biology and Proteomics, to the position of senior vice president and chief science officer.
LA JOLLA–Whether it’s making rash decisions or feeling grumpy, hunger can make us think and act differently—“hangry,” even. But little is known about how hunger signals in the gut communicate with the brain to change behavior. Now, Salk scientists are using worms as a model to examine the molecular underpinnings and help explain how hunger makes an organism sacrifice comfort and make risky decisions to get a meal.
LA JOLLA—Mammals can’t typically regenerate organs as efficiently as other vertebrates, such as fish and lizards. Now, Salk scientists have found a way to partially reset liver cells to more youthful states—allowing them to heal damaged tissue at a faster rate than previously observed. The results, published in Cell Reports on April 26, 2022, reveal that the use of reprogramming molecules can improve cell growth, leading to better liver tissue regeneration in mice.
LA JOLLA—Patients with colorectal cancer were among the first to receive targeted therapies. These drugs aim to block the cancer-causing proteins that trigger out-of-control cell growth while sparing healthy tissues. But some patients are not eligible for these treatments because they have cancer-promoting mutations that are believed to cause resistance to these drugs.
LA JOLLA—Salk Professors Joanne Chory, Joseph Ecker, Rusty Gage, Satchidananda Panda, Reuben Shaw and Kay Tye have been named to the Highly Cited Researchers list by Clarivate. The list identifies researchers who demonstrate “significant influence in their chosen field or fields through the publication of multiple highly cited papers.” Chory, Ecker and Gage have been named to this list every year since 2014, when the regular annual rankings began. This is Tye’s fifth, Shaw’s third and Panda’s first time receiving the designation. Additionally, Ecker appeared in two separate categories: “plant and animal science” and “molecular biology and genetics” and is one of 3.4 percent of researchers selected in two fields. Joseph Nery, a research assistant II in the Ecker lab, was also included on the list.
LA JOLLA—Salk scientists, collaborating with researchers from the University of Cambridge and Johns Hopkins University, have sequenced the genome of the world’s most widely used model plant species, Arabidopsis thaliana, at a level of detail never previously achieved. The study, published in Science on November 12, 2021, reveals the secrets of Arabidopsis chromosome regions called centromeres. The findings shed light on centromere evolution and provides insights into the genomic equivalent of black holes.
LA JOLLA—For the past fifteen years, cancer researchers have been using DNA sequencing technology to identify the gene mutations that cause different forms of cancer. Now, Salk Assistant Professor Edward Stites and his team of computational scientists have combined gene mutation information with cancer prevalence data to reveal the genetic basis of cancer in the entire population of cancer patients in the United States.
LA JOLLA—It takes billions of cells to make a human brain, and scientists have long struggled to map this complex network of neurons. Now, dozens of research teams around the country, led in part by Salk scientists, have made inroads into creating an atlas of the mouse brain as a first step toward a human brain atlas.
LA JOLLA—Salk Assistant Professor Graham McVicker has been awarded a National Human Genome Research Institute (NHGRI) Genomic Innovator Award, which supports early-career scientists who conduct innovative, creative research in genomics. The award, which provides $2.85 million over five years, is in recognition of McVicker’s efforts using computational and experimental approaches to investigate how human genetic diversity leads to metabolic, cardiovascular, autoimmune and other diseases.
LA JOLLA—When people think about the connection between genes and disease, they often envision something that works like a light switch: When the gene is normal, the person carrying it does not have the disease. If it gets mutated, a switch is flipped, and then they do have it.
LA JOLLA—The Salk Institute has promoted Diana Hargreaves to the rank of associate professor for her notable contributions in epigenetic regulation, which make specific regions of our DNA accessible to the machinery of cells. The promotion was based on recommendations by Salk faculty and nonresident fellows, and approved by President Rusty Gage and the Institute’s Board of Trustees.
LA JOLLA—Spinal cord nerve cells branching through the body resemble trees with limbs fanning out in every direction. But this image can also be used to tell the story of how these neurons, their jobs becoming more specialized over time, arose through developmental and evolutionary history. Salk researchers have, for the first time, traced the development of spinal cord neurons using genetic signatures and revealed how different subtypes of the cells may have evolved and ultimately function to regulate our body movements.
LA JOLLA—The ability to grow the cells of one species within an organism of a different species offers scientists a powerful tool for research and medicine. It’s an approach that could advance our understanding of early human development, disease onset and progression and aging; provide innovative platforms for drug evaluation; and address the critical need for transplantable organs. Yet developing such capabilities has been a formidable challenge.
LA JOLLA—Wolffia, also known as duckweed, is the fastest-growing plant known, but the genetics underlying this strange little plant’s success have long been a mystery to scientists. Now, thanks to advances in genome sequencing, researchers are learning what makes this plant unique—and, in the process, discovering some fundamental principles of plant biology and growth.
LA JOLLA—Lithium is considered the gold standard for treating bipolar disorder (BD), but nearly 70 percent of people with BD don’t respond to it. This leaves them at risk for debilitating, potentially life-threatening mood swings. Researchers at the Salk Institute have found that the culprit may lie in gene activity—or lack of it.
LA JOLLA and PALO ALTO, Calif.—The Salk Institute and BridgeBio Pharma, Inc. (Nasdaq: BBIO) today announced a three-year collaboration agreement formed to advance cutting-edge academic discoveries in genetically driven diseases toward therapeutic applications. Under the partnership, BridgeBio will help fund research programs from Salk’s world-renowned innovative cancer research, with the eventual goal of developing new therapeutics for patients in need.
LA JOLLA—The diabetes drug metformin—derived from a lilac plant that’s been used medicinally for more than a thousand years—has been prescribed to hundreds of millions of people worldwide as the frontline treatment for type 2 diabetes. Yet scientists don’t fully understand how the drug is so effective at controlling blood glucose.
LA JOLLA—In research that aims to illuminate the causes of human developmental disorders, Salk scientists have generated 168 new maps of chemical marks on strands of DNA—called methylation—in developing mice.
LA JOLLA—The human immune system is a finely-tuned machine, balancing when to release a cellular army to deal with pathogens, with when to rein in that army, stopping an onslaught from attacking the body itself. Now, Salk researchers have discovered a way to control regulatory T cells, immune cells that act as a cease-fire signal, telling the immune system when to stand down.
LA JOLLA—Chronic liver disease represents a major global public health problem affecting an estimated 844 million people, according to the World Health Organization. It is among the top causes of mortality in Australia, the UK and the United States. At the same time, it is both difficult to manage and there is no FDA-approved anti-fibrotic liver therapy. The microbiome—a complex collection of microbes that inhabit the gut—may be an unexpected indictor of health. Now, a collaborative team of Salk Institute and UC San Diego scientists have created a novel microbiome-based diagnostic tool that, with the accuracy of the best physicians, quickly and inexpensively identifies liver fibrosis and cirrhosis over 90 percent of the time in human patients.
LA JOLLA—Many cancer medications fail to effectively target the most commonly mutated cancer genes in humans, called RAS. Now, Salk Professor Geoffrey Wahl and a team of scientists have uncovered details of how normal RAS interacts with mutated RAS and other proteins in living cells for the first time. The findings, published in The Proceedings of the National Academy of Sciences on May 18, 2020, could aid in the development of better RAS-targeted cancer therapeutics.
LA JOLLA—Salk and Scripps Research Institute scientists, along with collaborators at the pharmaceutical company Lundbeck, identified two genes that can regulate levels of healthy fats, called FAHFAs, in mice. The team found that the loss of the two genes led to higher-than-normal levels of the beneficial FAHFAs, while blocking the genes’ activity with an experimental drug also increased FAHFA levels.
LA JOLLA—While scientists know of about 25,000 genes that code for biologically important proteins, additional, smaller genes hiding in our DNA may be just as important. But these tiny lines of genetic code have proven tough to track down.
LA JOLLA—Bright light at night interrupts the body’s normal day-night cycles, called circadian rhythms, and can trigger insomnia. In fact, circadian rhythms play a major role in health. Disrupted day-night cycles have even been linked to increased incidence of diseases like cancer, heart disease, obesity, depressive disorders and type 2 diabetes in people who work night shifts. Therefore, understanding how human eyes sense light could lead to “smart” lights that can prevent depression, foster sleep at night, and maintain healthy circadian rhythms.
LA JOLLA—Although graduating from school, a first job and marriage can be important events in life, some of the most significant events happen far earlier: in the first few days after a sperm fertilizes an egg and the cell begins to divide.
LA JOLLA—Breast cancer is one of the most prevalent cancers, and some forms rank among the most difficult to treat. Its various types and involvement of many different cells makes targeting such tumors difficult. Now, Salk Institute researchers have used a state-of-the-art technology to profile each cell during normal breast development in order to understand what goes wrong in cancer.
LA JOLLA—In 2017, Salk scientists reported that tilting a frozen protein sample as it sat under an electron microscope was an effective approach to acquiring better information about its structure and helping researchers understand a host of diseases ranging from HIV to cancer. Now, they have developed a mathematical framework that underlies some of those initial observations.
LA JOLLA—The brain’s prefrontal cortex, which gives us our ability to solve problems and plan ahead, contains billions of cells. But understanding the large diversity of cell types in this critical region, each with unique genetic and molecular properties, has been challenging.
LA JOLLA—The ability to edit genes in living organisms offers the opportunity to treat a plethora of inherited diseases. However, many types of gene-editing tools are unable to target critical areas of DNA, and creating such a technology has been difficult as living tissue contains diverse types of cells.
LA JOLLA—In the nucleus of every living cell, long strands of DNA are tightly folded into compact chromosomes. Now, thanks to a new computational approach developed at the Salk Institute, researchers can use the architecture of these chromosome folds to differentiate between types of cells. The information about each cell’s chromosome structure will give scientists a better understanding of how interactions between different regions of DNA play a role in health and disease. The study was published in the Proceedings of the National Academy of Sciences the week of July 8, 2019.
LA JOLLA—The Salk Institute announced that Helmsley-Salk Fellow Patrick Hsu has been named to MIT Technology Review’s prestigious annual list of Innovators Under 35. Every year, the media company recognizes a list of exceptionally talented technologists whose work has great potential to transform the world.
LA JOLLA—What makes us human, and where does this mysterious property of “humanness” come from? Humans are genetically similar to chimpanzees and bonobos, yet there exist obvious behavioral and cognitive differences. Now, researchers from the Salk Institute, in collaboration with researchers from the anthropology department at UC San Diego, have developed a strategy to more easily study the early development of human neurons compared with the neurons of nonhuman primates. The study, which appeared in eLife on February 7, 2019, offers scientists a novel tool for fundamental brain research.
LA JOLLA—We’ve all heard the expression: “what doesn’t kill you makes you stronger.” Now, research led by a Salk Institute scientist suggests why, at a cellular level, this might be true. The team reports that brief exposures to stressors can be beneficial by prompting the cell to trigger sustained production of antioxidants, molecules that help get rid of toxic cellular buildup related to normal metabolism.
LA JOLLA—One reason we’re supposed to eat a variety of colorful fruits and vegetables is because they contain nutritious compounds called antioxidants. These molecules counteract the damage to our bodies from harmful products of normal cells called reactive oxygen species (ROS).
LA JOLLA—Most people have heard of the CRISPR/Cas9 gene-editing technology, which acts as targeted molecular scissors to cut and replace disease-causing genes with healthy ones. But DNA is only part of the story; many genetic diseases are caused by problems with RNA, a working copy of DNA that is translated into proteins.
LA JOLLA—Is it better to do a task quickly and make mistakes, or to do it slowly but perfectly? When it comes to deciding how to fix breaks in DNA, cells face the same choice between two major repair pathways. The decision matters, because the wrong choice could cause even more DNA damage and lead to cancer.
LA JOLLA—Scientists have, for the first time, corrected a disease-causing mutation in early stage human embryos with gene editing. The technique, which uses the CRISPR-Cas9 system, corrected the mutation for a heart condition at the earliest stage of embryonic development so that the defect would not be passed on to future generations.
LA JOLLA—(May 4, 2017) Salk Institute scientists have developed a novel technology to correct disease-causing aberrations in the chemical tags on DNA that affect how genes are expressed. These types of chemical modifications, collectively referred to as epigenetics or the epigenome, are increasingly being considered as important as the genomic sequence itself in development and disease.
LA JOLLA—Salk scientists and collaborators have shed light on a longstanding question about what leads to variation in stem cells by comparing induced pluripotent stem cells (iPSCs) derived from identical twins. Even iPSCs made from the cells of twins, they found, have important differences, suggesting that not all variation between iPSC lines is rooted in genetics, since the twins have identical genes.
LA JOLLA—When scientists talk about laboratory stem cells being totipotent or pluripotent, they mean that the cells have the potential, like an embryo, to develop into any type of tissue in the body. What totipotent stem cells can do that pluripotent ones can’t do, however, is develop into tissues that support the embryo, like the placenta. These are called extra-embryonic tissues, and are vital in development and healthy growth.
LA JOLLA—FedEx, UPS, DHL—when it comes to sending packages, choices abound. But the most important delivery service you may not have heard of? mRNA. That’s short for messenger RNA, which is how your DNA sends blueprints to the protein-assembly factories of your cells. When a protein is faulty, delivering synthetic mRNA to cells could trigger production of a functional version. And that’s a message people with a variety of genetic diseases want to hear.
LA JOLLA—Most of us would be lost without Google maps or similar route-guidance technologies. And when those mapping tools include additional data about traffic or weather, we can navigate even more effectively. For scientists who navigate the mammalian genome to better understand genetic causes of disease, combining various types of data sets makes finding their way easier, too.
LA JOLLA—We all know how hard it is to find something small like a dropped contact lens that blends into the background. It’s similarly tough for biologists to find tiny proteins against the complex background of the cell. But, increasingly, scientists are learning that such microproteins, which are overlooked by traditional detection methods, also have important biological roles to play.
LA JOLLA—We put things into a container to keep them organized and safe. In cells, the nucleus has a similar role: keeping DNA protected and intact within an enveloping membrane. But a new study by Salk Institute scientists, detailed in the November 2 issue of Genes & Development, reveals that this cellular container acts on its contents to influence gene expression.
LA JOLLA—Mitochondria, the power generators in our cells, are essential for life. When they are under attack—from poisons, environmental stress or genetic mutations—cells wrench these power stations apart, strip out the damaged pieces and reassemble them into usable mitochondria.
LA JOLLA–Scientists have discovered a previously unknown wellspring of genetic diversity in humans, chimps and most other primates. This diversity arises from a new component of itinerant sections of genetic code known as jumping genes.
LA JOLLA–Healthy brain, muscle, eye and heart cells would improve the lives of tens of thousands of people around the world with debilitating mitochondrial diseases. Now, researchers at the Salk Institute have gotten one step closer to making such cures a reality: they’ve turned cells from patients into healthy, mutation-free stem cells that can then become any cell type. The new approach is described July 15, 2015 in Nature.