Our Mission is to develop new approaches for the prevention and treatment of infectious diseases and immunologic disorders. Department programs are integral to the School's new Initiative on Infectious Diseases. Researchers use state-of-the-art technologies of genomics, proteomics and imaging to study the genes and proteins of the pathogens and their hosts to identify novel targets for prevention and therapy.
Highly active anti-retroviral therapy (HAART) has helped millions survive the human immunodeficiency virus (HIV). Unfortunately, HIV has a built-in survival mechanism, creating reservoirs of latent, inactive virus that are invisible to both HAART and the immune system.
But now, researchers at UC Davis have identified a compound that activates latent HIV, offering the tantalizing possibility that the virus can be flushed out of the silent reservoirs and fully cured. Even better, the compound (PEP005) is already approved by the FDA. The study was published in the journal PLoS Pathogens.
“We are excited to have identified an outstanding candidate for HIV reactivation and eradication that is already approved and is being used in patients,” said lead author Satya Dandekar, who chairs the Department of Medical Microbiology and Immunology. “This molecule has great potential to advance into translational and clinical studies.”
While HAART has been quite successful – reducing HIV infection in newborns, restoring patients’ immune systems and lowering viral loads to virtually undetectable levels – these therapies cannot cure the disease alone. Once treatment is discontinued, pools of latent virus reactivate, and the infection comes roaring back. As a result, patients must remain on treatment indefinitely, posing the risk of long-term toxicity.
“We’ve made great progress, but at the end of the day you still have more than 30 million people walking around with HIV,” said Dandekar. “Without drugs, the virus can come back at the same threat level for patients. Eradicating HIV is extremely critical.”
Eradication means activating latent virus and destroying it, a strategy called “shock and kill.” Researchers around the world have been working on this approach, but finding the right compounds has been challenging. A successful molecule must precisely target proteins associated with HIV latency without overstimulating the immune system or wantonly activating protein master switches, such as NF-kappaB. Either outcome can generate severe side effects.
The UC Davis team may have succeeded with PEP005, the active ingredient in the FDA-approved anti-cancer drug PICATO, which increased HIV activation in patient blood samples and showed low toxicity. However, HIV is a complicated virus and, as clinicians have discovered with HAART, must be treated through multiple means. In addition to PEP005, the researchers tested other compounds capable of reactivating HIV through different pathways. This painstaking process identified another molecule, JQ1, which works synergistically with PEP005 to maximize HIV activation. PEP005 when combined with JQ1 increased HIV activation up to 15-fold. “A single treatment is not enough, which is why we are trying to hit HIV through two different pathways,” said first author Guochun Jiang. “As a result, we can see more dramatic viral activation.” While these results are promising, researchers are mindful that “shock” only works when it’s followed by “kill.”
Congratulations to Dr. Michael J. Leibowitz, professor, Medical Microbiology & Immunology as he was one of 6 UC Davis professors in newest class of AAAS fellows
The association announced the new class on Monday (Nov. 24). The membership elected 401 new fellows in all, in recognition of their contributions to innovation, education and scientific leadership. UC Davis, with its six new members, now has a total of 152 AAAS fellows.
The newest fellows:
Andreas Albrecht, chair, Department of Physics, internationally known for his work on theoretical cosmology. He was cited in particular for his work on the arrow of time and "slow roll" cosmic inflation, and for his service as vice chair and chair of the Astronomy and Astrophysics Advisory Committee that advises Congress and federal funding agencies, including NASA and the National Science Foundation.
Xinbin Chen, professor and veterinary oncologist, School of Veterinary Medicine and School of Medicine. His research focuses on the p53 gene and related proteins, known to play an important role in suppressing cancer. Chen and colleagues have found that p53 mutations — which can promote tumor formation — occur not only in people, but also in other mammals, including dogs, cats and horses.
Gino Cortopassi, professor of molecular biosciences, School of Veterinary Medicine. His research deals with the physiological mechanisms and potential therapeutics for diseases caused by dysfunctions of the cells’ mitochondria. His studies focus on Friedreich’s ataxia and Leber’s hereditary optic neuropathy, both mitochondrial neurodegenerative diseases caused by inherited mitochondrial defects.
Michael J. Leibowitz, professor of medical microbiology and immunology, recognized for his seminal discoveries on the biochemistry and genetics of RNA synthesis, modification and RNA virus-host interactions in yeast and HIV, as well as for his work to establish new educational and career development programs to promote diversity of the biomedical work force.
Deb Niemeier, professor, Department of Civil and Environmental Engineering, an expert on transportation-air quality and urban sustainability and the built environment. She was recognized for her distinguished contributions to energy and environmental science studies and policy development. She focuses at the interface of travel demand modeling and estimating mobile source emissions.
Diane Ullman, professor of entomology, whose research focuses on the interactions among insects, viruses and plants. She also studies the development of strategies for managing disease-causing microorganisms that are transmitted to plants by insects. Earlier this month she received the Entomological Society of America’s distinguished achievement award in teaching.
The association plans to recognize the new class of fellows — presenting each with a certificate and gold-and-blue rosette pin — on Saturday, Feb. 14, during the association’s annual meeting, to be held in San Jose.
Founded in 1848, the association aims to “advance science and serve society” through initiatives that include science policy, international programs, science education and public understanding of science.
Breast versus bottle feeding in rhesus monkeys
Infants receiving different diets after birth develop distinct immune systems
Dr. Dennis Hartigan-O'Connor recently had a study published in Science Translational Medicine on September 3, 2014, researchers from the California National Primate Research Center (CNPRC) at UC Davis and from UC San Francisco have shown that breast-and bottle-fed infant rhesus macaques develop different immune systems.
Diet has a strong influence on the intestinal microbiota in both humans and animal models. It is well established that microbial colonization is required for normal development of the immune system and that specific microbial constituents prompt the differentiation or expansion of certain immune cell subsets. Nonetheless, it has been unclear how profoundly diet might shape the primate immune system or how durable the influence might be. We show that breast-fed and bottle-fed infant rhesus macaques develop markedly different immune systems, which remain different 6 months after weaning when the animals begin receiving identical diets. In particular, breast-fed infants develop robust populations of memory T cells as well as T helper 17 (TH17) cells within the memory pool, whereas bottle-fed infants do not. These findings may partly explain the variation in human susceptibility to conditions with an immune basis, as well as the variable protection against certain infectious diseases.
Read more here, Published in Science Translational Medicine
Diseases on the move because of climate change
Dr. George Thompson, Assistant Professor in the Department of Medical Microbiology and Immunology, was interviewed as part of a USA today article highlighting how climate change is affecting the movement of infectious diseases across the United States. Dr. Thompson is a specialist on Valley Fever, which has seen a ten-fold increase in infections since 1998.
Surviving Valley Fever
Severe case of highlights importance of awareness, expert care
For seven months beginning in the fall of 2010, Virginia Cappel’s medical condition was touch-and-go.
The series of events that would change her life began simply, with flu-like symptoms, which Virginia and her husband Niels initially thought was bronchitis. But about a month later, when they left their home in Davis, Calif., for a vacation in the Midwest, Niels began to notice more ominous signs: disruptions in Virginia’s speech, a slower gait and confusion, such as associating the wrong words with activities.
An immediate trip to the emergency room ruled out a stroke, and during the next few weeks, the diagnosis would continue to shift. There was concern that she had bacterial meningitis, followed by viral meningitis. Finally, a neurologist diagnosed valley fever, a fungal infection that affects about 150,000 people in the U.S. each year and has been on the rise in California. According to the California Department of Public Health, the number of reported cases in California has increased six-fold, from about 816 cases in 2000 to more than 5,366 cases in 2011.