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At the Forefront of Genetics Research
Natural Killer Cells & HIV

"The association of HLA with HIV disease progression is very well known, yet to date, no one has studied the full KIR complex, including all KIR loci, in HIV infection or disease progression."

CHORI scientist Elizabeth Trachtenberg, PhD, a geneticist and clinical research investigator for CHORI’s Center for Genetics and Center for Cancer, has recently landed 3 highly competitive grants to investigate the role of natural killer (NK) cells in multiple sclerosis (MS), HIV and organ transplantation. This month will highlight Dr. Trachtenberg’s 5 year, $603,000 HIV grant, which proposes to map the genetic variation of the NK cells’ surface receptors which recognize HLA class I ligands – called killer-immunoglobin-like receptors (KIR) – to disease markers and NK cell function in a cohort of recently HIV infected adults.

Approximately 40 million people are infected with HIV worldwide, while in some parts of Africa it's been suggested that 50 percent of the population is infected. As a result, HIV represents one of the greatest global health challenges of the 21st century. Finding new ways to prevent, halt and treat the infection is paramount, and Dr. Trachtenberg's latest grant presents a potential avenue to do so.

"We'll be looking at disease progression in order to try to develop new immunological methods for the prevention and control of HIV infection and disease progression," explains Dr. Trachtenberg, who notes the both the intriguing yet highly incomplete evidence to date on the role of KIR and NK function in HIV.

This is due in great part to the complexity of the KIR complex, which has anywhere between 7 and 17 genes in all different combinations of inhibitory or stimulatory forms per any given individual. Previous studies have focused on just a fraction of the KIR loci, and often have yielded conflicting results. Now, however, Dr. Trachtenberg has the potential to crack the KIR/HIV code, using the novel high through-put KIR analysis she and her colleagues developed.

"In the past, these analyses required much larger DNA quantities, were hugely time consum-ing and not always accurate."
"Now we can use very tiny amounts of DNA and produce highly accurate results very efficiently," says Dr. Trachtenberg. "It's given us a big jump on the KIR genetics and molecular epidemiology arenas."

The novel technique was key in garnering the latest grant, allowing Dr. Trachtenberg and her colleagues to utilize the KIR and HLA disease association analysis to try to better understand the role of these two gene complexes in disease susceptibility or protection, and to figure out how these innate immune complexes work together in defense against infection.
"We're hoping that by understanding these innate and adaptive complexes that we'll be able to develop new methods to manipulate the immune system for therapeutic benefit," says Dr. Trachtenberg.

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