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).
Led an analysis of data on more than 1,600 older Americans and concluded that loneliness is independently associated with an increased rate of death 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.
Concluded that short-term memory loss may be due to distraction and that short-term memory and multitasking can be improved through training in both the young and old. (Adam Gazzaley, MD, PhD)
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.
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 that heredity 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)
- Reported the first direct evidence that a tiny filament extending from cells, known as primary cilia, may play a role in the most common malignant brain tumor in children and in a type of skin cancer known as basal cell carcinoma. The findings, conducted by two separate UCSF teams, suggest that drugs that boost or block primary cilia activity could offer a new strategy against cancer. (Arturo Alvarez-Buylla, PhD; and Jeremy Reiter, MD, PhD)
- Developed a new prostate cancer risk assessment test that gives patients and their doctors a better way of gauging long-term risks and pinpointing high-risk cases. The test, known as CAPRA, predicts the incidence of bone metastases, prostate cancer deaths and deaths from other causes. (Matthew R. Cooperberg, MD, MPH)
- Discovered the first gene involved in regulating the optimal length of human sleep, which is critical to human physical and mental health. The discovery is significant for future development of interventions to alleviate pathologies associated with sleep disturbance. (Ying-Hui Fu, PhD)
- Found that simple, inexpensive, high-flow oxygen is an effective treatment for cluster headache pain, providing relief for the disorder without drugs and their potential side effects. (Peter Goadsby, MD, PhD)
- Performed the 10,000th procedure in the UCSF Organ Transplant Service, one of the largest and oldest in the world. Founded in the 1960s, the service now includes heart, intestinal, kidney, liver, lung and pancreas transplants. UCSF pioneered many advances in the field, and the UCSF service is recognized as the gold standard for other transplant centers. (Nancy Ascher, MD; John Roberts, MD; and Charles Hoopes, MD)
- Reported new data showing how language is organized within the cortex of the human brain, making it possible to use an innovative technique called negative brain mapping to safely remove tumors near language pathways of the brain. The technique minimizes brain exposure and reduces the amount of time the patient must be awake during surgery. Since the mid-1990s, a UCSF team has conducted pioneering work in brain mapping, a specialty within the neurosciences in which the neurophysiological properties of the brain are charted. (Mitchel Berger, MD)
- Reported that paramedics equipped with pre-hospital electrocardiographic (ECG) devices that wirelessly transmit critical information to emergency rooms while in route to the hospital can reduce the time it takes to diagnose and treat heart attack patients by more than 30 percent. The time reduction is linked to survival and lower risk of permanent heart muscle damage. (Barbara Drew, RN, PhD)
- Identified several new genes associated with increased risk of heart attack, suggesting the existence of some previously unrecognized mechanisms and potential new strategies for risk reduction. (John Kane, MD; and Mary Malloy, MD)
- Determined that smoked cannabis reduces pain caused by HIV-associated neuropathy, the first measurable benefit for medical marijuana shown in a gold standard, double-blind, placebo-controlled clinical trial. (Donald Abrams, MD)
- Determined that high-calorie, low-fiber Western diets promote hormonal imbalances that encourage children to overeat, thereby fueling the epidemic of pediatric obesity, now the most commonly diagnosed childhood ailment. (Robert Lustig, MD)
- Reduced the incidence of malaria to almost zero (by 97 percent) among children with HIV in Uganda by administering prophylactically an inexpensive antibiotic and providing insecticide-treated mosquito nets for coverage while sleeping. (Diane Havlir, MD)
- Found that eating lots of fruits and vegetables, especially vegetables, is associated with a 50 percent reduction in the risk of developing pancreatic cancer. (Elizabeth Holly, PhD, MPH)
- Discovered a ribbon of neural stem cells that potentially could be used to develop strategies for regenerating damaged brain tissue – and that could offer new insight into the most common type of brain tumor. (Arturo Alvarez-Buylla, PhD)