It is no small task to recount the major basic science and clinical research accomplishments that span the history of UC San Francisco. Here is a fairly comprehensive list that gives credit to the researchers who took the lead to make these discoveries dating back to 1914.
UCSF’s Nobel laureates are, from left, Shinya Yamanaka (2012), Elizabeth Blackburn (2009), Stanley Prusiner (1997), and co-recipients J. Michael Bishop and Harold Varmus (1989).
- Identified an experimental drug, neratinib, as demonstrating benefit for some women with newly-diagnosed, high-risk breast cancer. (Laura J. Esserman, MD, MBA)
- Found that e-cigarettes might be a new route to smoking and nicotine for teenagers. In the first analysis of the relationship between e-cigarette use and smoking among adolescents in the United States, the researchers learned that adolescents who used the devices were more likely to smoke conventional cigarettes and less likely to quit smoking. (Stanton A. Glantz, PhD)
- Has the highest one-year survival rate in the nation, among institutions performing more than 20 adult lung transplants each year, according to data from the Scientific Registry of Transplant Recipients (STTR), a national database of transplant statistics. It also is the only program to have achieved significantly better than expected outcomes for two consecutive report cycles from SRTR.
- Found the use of catheter ablation is not only beneficial for treating atrial flutter but also can significantly reduce hospital visits – both inpatient and emergency – and lower the risk for atrial fibrillation. It’s a procedure frequently performed at UCSF, even on people in their 90s.
- A team led by UCSF scientists in the laboratory of Matthew W. State, MD, PhD, shows that the disruption of a single type of cell – in a particular brain region and at a particular time in brain development – is a significant factor in the emergence of autism. The finding marks a turning point in research on autism spectrum disorders.
- UCSF researchers led by Kevan Shokat, PhD, create small molecules that irreversibly target a mutant form of the protein called ras—the driver of most cancers--without binding to the normal form. This feature distinguishes the molecules from all other targeted drug treatments in cancer to date. When tested on human lung cancer cells grown in culture, the molecules efficiently killed the ras-driven cancer cells.
- In a technical tour de force, UCSF scientists in the laboratories of Yifan Cheng, PhD, and David Julius, PhD, and determine, at near-atomic resolution, the structure of TRPV1, a protein that plays a central role in the perception of pain and heat. The research is a watershed for the field of structural biology, which aims to discover how proteins are physically constructed in order to better understand their function.
- UCSF researchers led by Edward F. Chang, MD, provide a detailed account of how speech sounds are identified by the human brain, offering an unprecedented insight into the basis of human language. Scientists have known for some time the location in the brain where speech sounds are interpreted, but little has been discovered about how this process works, and the findings may add to our understanding of language disorders, including dyslexia.
- An international multi-center study led by researchers from UCSF Benioff Children’s Hospital was the first to evaluate whether purified cannabinoid is effective in treating severe forms of childhood epilepsy that do not respond to standard antiepileptic drugs. (Maria Roberta Cilio, MD)
- Discovered that infants ‘catch’ and embody the physiological residue of their mother’s stressful experiences. These findings shed light on how health and wellbeing can have long-term consequences, transferring across generations. (Wendy Berry Mendes, Phd)
- Found that despite its potentially harmful effects in children, codeine continues to be prescribed in U.S. emergency rooms. Because of variability in how children process the drug, about a third receive no symptom relief from taking it, while up to one in 12 can accumulate toxic amounts causing breathing to slow down and possible death. The research was the first to identify to what extent codeine was being prescribed to children in US emergency rooms, where it can be prescribed for common complaints such as painful injuries and coughs and colds. (Sunitha Kaiser, MD)
- Discovered that certain rare cells extracted from adult breast tissue can be instructed to become different types of cells, a discovery that could have important potential for regenerative medicine. The newly-found cells are pluripotent, or capable of turning into most cell types, and when placed either in mice, or in cell culture, the cells could differentiate to produce multiple cell types, including those that proceed to make heart, intestine, brain, pancreas and even cartilage. (Thea D. Tlsty, PhD)
- Found that women with harmful mutations in the BRCA gene, which put them at higher risk of developing breast and ovarian cancer, tend to undergo menopause significantly sooner than other women, allowing them an even briefer reproductive window and possibly a higher risk of infertility. (Mitchell Rosen, MD)
- Learned that exposure in infancy to nitrogen dioxide (NO2), a component of motor vehicle air pollution, is strongly linked with later development of childhood asthma among African Americans and Latinos. For every five parts per billion increase in NO2 exposure during the first year of life, there was a 17 percent increase in the risk of developing asthma later in life. (Esteban G. Burchard, MD, MPH)
- Developed a two-minute tool to help hospital staff predict a patient’s risk of delirium, a change in mental cognition characterized by severe confusion and disorientation that can prolong hospital stays. (Vanja C. Douglas, MD)
- Determined that men with prostate cancer could significantly improve their survival chances by substituting healthy vegetable fats – such as olive and canola oils, nuts, seeds and avocados – for animal fats and carbohydrates. Men who replaced 10 percent of their total daily calories from carbohydrates with healthy vegetable fats had a 29 percent lower risk of developing lethal prostate cancer and a 26 percent lower risk of dying from all causes. (June M. Chan, ScD)
- Proposed a major update to the way cancer is diagnosed and defined, including reclassifying premalignant/indolent conditions and developing molecular diagnostic tools to identify low-risk lesions. (Laura J. Esserman, MD, MBA)
- Found a clear association between certain genes and the development of lymphedema, a painful, chronic condition that often occurs after breast cancer surgery and some other cancer treatments. The study was the first to evaluate genetic predictors of lymphedema in a large group of women using spectroscopy to measure increases in fluid in the arm. Researchers learned for the first time that the risks of developing lymphedema increased significantly for women with more advanced breast cancer at the time of diagnosis, more lymph nodes removed or a significantly higher body mass index. (Bradley Aouizerat, PhD)
- Won a $9.45 million federal grant to “transform and revolutionize” the treatment of prostate cancer, the second most common form of cancer among American men. Intended to overhaul the clinical management of prostate cancer for men newly diagnosed with the disease, UCSF scientists led by Peter Carroll, MD, MPH, will develop and validate a novel risk-prediction model to provide better information about the patient’s true risk of cancer progression.
- Launched the Health eHeart study to better understand how the heart functions and to develop news ways to predict and prevent cardiovascular disease. The innovative study – funded by the Salesforce.com Foundation – aims to enroll 1 million people worldwide, with Jeffrey Olgin, MD, Mark Pletcher, MD, MPH, and Gregory Marcus, MD, MAS, as principal investigators.
- Learned how having two attending surgeons in the operating room during spinal surgeries can benefit patients in multiple ways. Christopher Ames, MD, who led the study with Vedat Deviren, MD, found these surgeries tended to be much shorter while patients suffered less blood loss, had fewer major complications and enjoyed shorter hospital stays.
- A team of top Silicon Valley entrepreneurs launch The Breakthrough Prize in Life Sciences at a UCSF press conference. The new prize, which carries a cash award twice as large as the Nobel Prize, is “dedicated to advancing breakthrough research, celebrating scientists and generating excitement about the pursuit of science as a career.” The prize’s co-founders are Anne Wojcicki, co-founder of the genetic testing company 23andMe; Yuri Milner, founder of the internet company Mail.ru Group; Facebook founder Mark Zuckerberg and his wife, Priscilla Chan, MD; and Google co-founder Sergey Brin.
- UCSF researchers in the laboratory of Nirao M. Shah, MD, PhD, discovered a sensory system in the foreleg of the fruit fly that tells male flies whether a potential mate is from a different species. The work addresses a central problem in evolution that's poorly understood: how animals of one species know not to mate with animals of other species.
- A drug developed by UCSF’s Jeffrey Bluestone, PhD, is strikingly effective over two years in about half of the patients who participated in a phase 2 clinical trial. Patients who benefited most were those who still had relatively good control of their blood sugar levels and only a moderate need for insulin injections when the trial began. With the experimental drug, teplizumab, they were able to maintain their level of insulin production for the full two years – longer than with most other drugs tested against the disease.
- In a groundbreaking study, UC San Francisco researchers found that children affected with sensory processing disorder have quantifiable differences in brain structure, for the first time showing a biological basis for the disease that sets it apart from other neurodevelopment disorders. Sensory processing disorders (SPD) are more prevalent in children than autism and as common as attention deficit hyperactivity disorder, yet the condition receives far less attention partly because it’s never been recognized as a distinct disease. (Elysa Marco, MD; Pratik Mukherjee, MD, PHD)
- Found a new way a known cellular structure passes along instructions critical to the formation of the limbs and digits of developing embryos, a finding likely to fundamentally reshape biologists' understanding of how cells communicate to each other during development.
- Led an analysis of data on more than 1,600 older Americans and concluded that and functional decline. Even those who live with partners may report that they often feel lonely.Carla Perissinotto, MD, MHS, found that everything from inheritance, to how we eat, to whom we live with now appears to affect aging.
- Found that smokers who switched to cigarettes with tobacco that contains less nicotine did not compensate by smoking more cigarettes and inhaling more tar and toxins. Neal Benowitz, MD, reported that it might be possible to free smokers from addiction by gradually lowering the amount of nicotine in cigarettes.
- Found evidence that a protein which leaks from blood into the brain acts as an early trigger that sets off the brain’s inflammatory response in multiple sclerosis. (Katerina Akassoglou, PhD)
- Discovered cells of the blood cancers known as lymphomas often contain mutations that allow them to evade the cell-suicide program as they activate the unfolded protein response to meet their outsized protein demands. (Davide Ruggero, PhD)
- Showed that radiation exposure through medical imaging exams is increasing, with some exams being unnecessary or exposing patients to higher-than-necessary radiation doses. (Rebecca Smith-Bindman, MD)
- Demonstrated that paramedics using an autoinjector to inject an anticonvulsive treatment directly into the thigh were able to stop epileptic seizures more quickly and effectively than they could by giving an anticonvulsant through an IV line. J. Claude Hemphill III, MD, MAS, chief of neurology at the UCSF-affiliated San Francisco General Hospital and Trauma Center, led the clinical trials.
- Found that an experimental drug cures hookworm in hamsters and suggested that similar drugs might be effective in humans. Conor Caffrey, PhD, directed the study in hamsters in which he used an experimental drug to target a key “protease” enzyme in the parasite’s gut that helps it digest a blood meal.
- Found that an inexpensive arthritis drug kills parasites that cause dysentery. James McKerrow, MD, PhD, and his UCSF and UC San Diego collaborators have planned clinical trials to use the drug to target these dysentery-causing amoebas, as well as the parasite that causes giardia.
- Reported studies that may help explain why women appear to be at higher risk for Post Traumatic Stress Disorder (PTSD) following trauma, and why they may face greater health risks from PTSD. One study, reported by Sabra Inslicht, PhD, suggested that women with PTSD have greater fear responses than men. Another study, reported by Aoife O’Donovan, PhD, concluded that women with PTSD are more likely to experience aging at the cellular level.
- Called on patient advocates to push for regulations to make clinical and research data more usable while protecting patient privacy. UCSF leaders are exploring bioinformatics projects that might serve as pilots for using data more powerfully for scientific discovery and to more precisely diagnose and treat each patient’s ills. UCSF Chancellor Susan Desmond-Hellmann, MD, MPH, in 2011 co-chaired a National Academy of Sciences Committee that recommended the creation of an extensive data network to revolutionize medical discovery, diagnosis and treatment, an emerging field called precision medicine.
- Conducted the second neural stem cell clinical trial ever in the United States – and the first with published results. David H. Rowitch, MD, PhD, a professor of pediatrics and neurological surgery, treated young children with Pelizaeus-Merzbacher disease (PMD). In PMD, myelin, a fatty sheath needed to insulate nerves, is not produced. Rowitch and colleagues showed that the transplanted neural cells were successfully engrafted in the brain and produced myelin.
- Reprogrammed skin cells to form an interconnected, functional network of brain cells, using a single genetic factor.The study, led by Gladstone scientist Yadong Huang, MD, PhD, involved Li Qian, PhD, and Deepak Srivastava, MD, who used three factors injected into damaged hearts to convert scar-forming cells into beating heart muscle cells that improved blood pumping.
- Observed 30 years of leadership in AIDS research after the first cases were reported in San Francisco. UCSF and San Francisco General Hospital (SFGH) continue to set the standard for translating research discoveries into better HIV/AIDS treatment, and these medical centers remain top-ranked for HIV care by US News & World Report. UCSF physicians also are leading major international efforts to combat the disease worldwide. UCSF researchers are conducting trailblazing research showing the effectiveness of treatment at diagnosis for preventing the spread of HIV infection, the role of HIV infection in aging and implications for patient care, and the potential of treatments that could lead to an HIV cure.
- Performed whole-genome genotyping of the DNA of 100,000 Kaiser Permanente members who agreed to take part in the nation’s largest and most diverse genomics project. The UCSF arm of the project, led by Neil Risch, PhD, director of the UCSF Institute for Human Genetics, and Pui-Yan Kwok, MD, PhD, also worked with researchers in UCSF Nobel laureate Elizabeth Blackburn’s laboratory to analyze the length of the protective tips on the chromosomes in each sample. These structures, called telomeres, are beginning to be linked to chronic disease and aging. The genotyping and telomere data ultimately will be linked with patients’ health records to accelerate research into the connections between genetics, environment and health.
- Showed that prenatal exposure to cigarette smoke far outweighed the role of exposure to cigarettes after birth. In fact, children with severe asthma were 3.6 times more likely to have been exposed to tobacco smoking before birth than children with a mild form of the disease, even if they were not exposed at all during childhood. The research could have a direct impact on public health campaigns, as more than one in seven pregnant women smoke in the United States. (Esteban Burchard, MD, and Haig Tcheurekdjian, MD, a professor at Case Western Reserve University)
- Reduced hospital readmissions for older heart failure patients by 30 percent. UCSF Medical Center's Heart Failure Program reduced both 30-day and 90-day readmissions for patients 65 and older through the program, launched in 2008 with a $575,000 grant from the Gordon and Betty Moore Foundation. The program has cut Medicare billing by at least $1 million annually at UCSF, while freeing up hospital beds for other patients.
- Showed thatheredity in autism is overshadowed by environmental factors, possibly in the fetal environment. The study, the largest and most rigorous autism study to date on twins in which at least twin was affected by autism, found that the children’s environment represents more than half of the susceptibility — 55 percent in the most severe form of autism and 58 percent in the broad spectrum of the disorder. The collaborative work tapped expertise from the UCSF Institute for Human Genetics and Stanford University — which jointly led the research — as well as from Kaiser Permanente, UC Davis, the Autism Genetic Research Exchange and the California Department of Public Health. (Neil Risch, PhD, Joachim Hallmayer, MD, Lisa Croen, PhD, at Kaiser Permanente, and epidemiologist Judith Grether, PhD, at the California Department of Public Health)
- Proved definitively that fetal surgery can help repair the birth defect spina bifida. Babies who undergo the prenatal procedure experience fewer neurologic complications than babies who have corrective surgery after birth, according to findings from a major multicenter randomized trial led by UCSF researchers. The study, funded by the National Institutes of Health, is the first to systematically evaluate the best treatment for myelomeningocele, the most serious form of spina bifida, in which the bones of the spine do not fully form. The surgical procedures evaluated in the trial were developed at the UCSF Fetal Treatment Center under the direction of Michael Harrison, MD, a UCSF professor emeritus considered the “Father of Fetal Surgery.”
- First use in humans of a new technology that monitors changes in hyperpolarized pyruvate, a naturally occurring sugar that cells produce during metabolism, in order to rapidly assess the aggressiveness of a tumor by imaging its metabolism. The technique has the potential for dramatically changing treatment for many types of tumors by providing immediate feedback to clinicians on whether a therapy is working. (Sarah Nelson, PhD; Daniel Vigneron, PhD; John Kurhanewicz, PhD; Marcus Ferrone, PharmD; and Andrea Harzstark, MD, with colleagues at GE Healthcare)
- Discovered a new stem cell in the developing human brain that accounts for the dramatic expansion of the region in the lineages that lead to man. Further studies of these cells are expected to shed light on autism, schizophrenia and malformations of brain development, including microcephaly, lissencephaly and neuronal migration disorders, as well as age-related illnesses such as Alzheimer’s disease. (Arnold Kriegstein, MD, PhD)
- Found that a single dose of radiation administered during surgery is as effective for patients with early forms of breast cancer as standard radiation therapy taking as long as six weeks. The finding is significant in both time and expense for patients. (Michael Alvarado, MD)
- Identified a molecular regulator (Hv1) that controls the ability of human sperm to reach and fertilize an egg, evidence that is key in both treating male infertility and preventing pregnancy. (Yuriy Kirichok, PhD)
- Determined that reducing salt in the American diet by as little as one-half teaspoon a day could prevent nearly 100,000 heart attacks and 92,000 deaths a year. (Kirsten Bibbins-Domingo, MD, PhD, with colleagues at Stanford University and Columbia University)