Battleground at the Cellular Level
ByIn their Higgins Hall lab, Associate Professor of Biology Ken Williams and his researchers survey the biological battleground of a deadly disease.
Using cutting-edge molecular techniques, researchers paint cells bright colors to track their attack over the years, pick apart genes at the molecular level and look for ways to shore up beleaguered immune systems.
Understanding and combating the carnage wrought by HIV and AIDS at the cellular level is the primary target of the Williams lab, where researchers work to decipher the genetic and cellular mysteries of the deadly disease and gauge the potential for gene therapy to fight the effects of HIV and AIDS, particularly in the brain, where the reach of drug therapies falter.
Among the many questions posed by a virus that mutates with startling unpredictability one stands out: Is it the virus itself or the immune system’s own defensive response that does the most damage to the brain as the disease progresses?
“The big question is whether it’s the immune system coming into the brain that drives brain disease in patients with HIV and AIDS,” says Williams. “If it is, can you block or moderate the virus and the damage it does? Drugs don’t penetrate the brain very well, but cells traffic into the brain. If we can modulate the virus outside of the brain, we think we can more effectively target the disease.”
In his third year at BC, Williams has assembled a lab consisting of senior scientists, post-docs, graduate students and undergraduate biology majors working at the forefront of neuro-biological research, attracting the attention of scientists from around the world and drawing research funding from agencies focused on disease prevention.
Post-doc researcher Caroline Soulas and flow cytometry specialist Patrick Autissier traveled to the Keystone Meeting in Canada in March to report on the advanced techniques Autissier developed for sorting genetic markers, which Soulas then used to identify a single immune cell population that expands with AIDS, giving researchers a first indication of a target cell that takes the infection to other cells.
In April, Williams was part of a select group of scientists invited to Italy to speak at a meeting convened by the US National Institutes of Health to focus on cells critical to immune response. A recent article from the Williams lab in the American Journal of Pathology reports genetically-modified cells that decrease a receptor for HIV continue to penetrate the brain for as long as four years after initial gene therapy, suggesting that a population of cells that cannot be HIV infected can repopulate the brain.
“For people doing gene therapy to stop HIV infection, these results rate a 9 on a scale of 10,” said Williams. “It’s fantastic news.”
A paper from Williams and collaborators from Harvard Medical School in the journal Neurology reported success using clinical immunology and brain imaging to demonstrate in early HIV-infected humans that the white blood cells that control viral growth in blood also contribute to brain injury.
Williams joined BC after 11 years at Harvard Medical School, bringing along a research portfolio focused on immunology, virology, disease development and the interaction of the central nervous system and the immune system. The professor’s lab, which receives nearly $2 million in external funding a year, includes a dozen researchers who use viral infection models, histology and confocal microscopy to study the effects of HIV and AIDS on the brain. Researchers are also using other cutting-edge tools, including laser flow cytometry and cell sorting technology.
Williams’ research program has been consistently supported by grants from the National Institutes of Health. He currently has three RO1 grants, among the most sought-after by researchers in health and biological sciences, and projects in areas of HIV therapy, reversing dementia in AIDS patients and studying a range of AIDS-related illnesses and the interplay of the virus with blood cells, the brain, immune system response and anti-retroviral therapy.
Earlier this year, Williams and colleagues from the University of Florida received a five-year, $3.5-million grant from the NIH to investigate what genetic changes occur during HIV infection of the brain.
Williams will be working with UF computational biologist Marco Salemi, whose theoretical experts will be mapping the evolution of the disease using DNA sequences, mathematical models, computer algorithms and visualization techniques. The Williams lab will compare those findings to actual examples of the disease through its expertise in the use of animal models to study an HIV-like disease, called SIV, which affects monkeys.
Salemi says pairing labs with two unique approaches to research is an exciting prospect.
“Ken and I have been talking about collaborating and now we’re putting this into action,” he said. “Ken goes for the straight answer. He wants to see something with applications. I think we balance each other and I think this is a model for how 21st-century biological
research can be done. Put together the best in theoretical and experimental biology and get the best of both worlds.”
Ed Hayward can be reached at firstname.lastname@example.org