UCSD physicians will participate in a study led by Julio Montaner, M.D., at the University of British Columbia as part of the inaugural Avant-Garde Award from the National Institute on Drug Abuse (NIDA). Intended to stimulate innovative, high-impact research, the Avant-Garde Awards – $500,000 per year for five years – are for groundbreaking work that may lead to innovations in the prevention and treatment of HIV/AIDS in drug users. The award will be used to evaluate of the effectiveness of expanded access to highly active antiretroviral therapy (HAART) by injection drug users in order to lower the number of new cases of HIV infection in this high-risk group. Montaner’s project, called STOP HIV/AIDS, will coordinate research being done in Canada with HIV researchers based at UC San Diego. The study affords researchers a unique opportunity to gauge the program’s success because injection drugs users can be enrolled in and tracked through Canada’s national Health Care System. These studies will complement the global efforts in HIV-related research already underway at UC San Diego’s HIV Neurobehavioral Research Center, headed by Igor Grant, M.D., as well as work to prevent the spread of HIV infection among injection drug users in Mexico and other countries, led by Steffanie Strathdee, Ph.D., and Thomas L. Patterson, Ph.D., co-principal investigator on this grant.

Investigators from neurosciences, chemistry and medicine, as well as the San Diego Supercomputer Center (SDSC) have investigated how proteins involved in neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease interact to form unique complexes. Their findings explain why Alzheimer’s patients might develop Parkinson’s, and vice versa. The new and unique molecular structures they discovered can now be used to model and develop new drugs for these devastating neurological diseases. The team, led by Eliezer Masliah, M.D., found that "fatal" or abnormal interactions among the a-synuclein protein (α-syn, involved in Parkinson’s disease) and Abeta amyloid (Aβ, which leads to the plaques associated with Alzheimer’s disease) interact and form unique "hybrid" complexes. These hybrid abnormal protein interactions result in combined neurodegenerative diseases.

Jamey Marth, Ph.D., has come up with a unified molecular view of the indivisible unit of life, the cell, which may provide an answer to the question of why the origins of many serious diseases remain a mystery. Reviewing findings from multiple disciplines, Marth realized that only 68 molecular building blocks are used to construct these four fundamental components of cells: the nucleic acids (DNA and RNA), proteins, glycans and lipids. His work, which illustrates the primary composition of all cells, is published in the September issue of Nature Cell Biology. Like the periodic table of elements, first published in 1869 by Russian chemist Dmitri Mendeleev, is to chemistry, Marth’s visual metaphor offers a new framework for biologists. This new illustration defines the basic molecular building blocks of life and currently includes 32 glycans (sugar linkages found throughout the cell) and eight kinds of lipids (which compose cell membranes) along with the more well-known 20 amino acids that are used to make proteins and the eight nucleosides that compose the nucleic acids, DNA and RNA. According to Marth, these 68 building blocks provide the structural basis for the molecular choreography that constitutes the entire life of a cell, and two of the four cellular components are produced by these molecular building blocks in processes that cannot be encoded by the genes. These cellular components – the glycans and lipids – may now hold the keys to uncovering the origins of many grievous diseases that continue to evade understanding.

Researchers at the Moores UCSD Cancer Center have found evidence explaining why a common chemotherapy drug, cisplatin, may not always work for every cancer patient. They have shown that when a variant version of a key protein that normally causes cell death is active, patients may be resistant to the cancer-killing drug. The scientists say that such findings are important to understanding how personalized therapies may be developed for patients. In a series of experiments, Jean Wang, Ph.D., Richard Kolodner, Ph.D., and their co-workers found evidence that when a specific variant form of a so-called "mismatch repair" protein, PMS2, is active, cisplatin doesn’t kill cancer cells the way it normally does. The cancer is, in effect, resistant to the drug. As a repair protein, PMS2 is crucial to fixing mistakes in DNA that may occur during replication. It also has a darker side, playing a role in instructing cells to kill themselves.