Dr. Malamud operates the oral-based diagnostic machine that could one day be in millions of homes.
By Christopher James, NYU Press Officer
Decades ago, when he was an undergraduate at the University of Michigan, Dr. Daniel Malamud was trying to settle on a career path. The career counselor at Michigan felt he was not well-suited to be a scientist ó his test results showed him to be a rather outgoing person, one who likes people and group interactions ó and thought perhaps he should be considering a career in medicine.
"My counselor told me, ĎScience is a solitary profession,í" said Dr. Malamud, "but nothing could have been further from the truth. In fact, scientists are very social creatures because science is so complex that you need to interact with a lot of people. And I think one of the things that Iíve enjoyed most in science is the social interaction with very smart people from different backgrounds."
Today, Dr. Malamud, a biochemist by training, is one of the leading researchers in the fields specializing in anti-HIV agents and oral-based diagnostics. Last spring, Dr. Malamud joined the NYU College of Dentistry, from the University of Pennsylvania, as a Professor of Basic Science and Craniofacial Biology and Director of the HIV/AIDS Research Program at NYUCD. Dr. Malamud was recruited with the support of a $750,000 award from the New York State Office of Science, Technology and Academic Research (NYSTAR) Faculty Development Program, which assists universities in the recruitment and retention of leading research faculty in science and technology fields with strong commercial potential. One part of Dr. Malamudís research deals with HIV pathogenesis and the design of anti-HIV drugs. He is also concurrently researching novel diagnostic techniques using oral samples.
Dr. Malamud first became interested in salivary proteins in his first position in the Department of Surgery at Massachusetts General Hospital. He was studying the phenomenon of why animals lick their wounds. In the course of interacting with surgeons, he was struck by the fact that abdominal surgery required a highly sterile environment, while oral surgery did not.
"If you do oral surgery, if you pull out a tooth or if you do periodontal surgery, or even if you bite your cheek, despite the fact that thereís hundreds of thousands of bacteria in your mouth ó a whole range of types and species, and viruses ó you almost never get an infection," said Dr. Malamud. "Also, wounds in the mouth heal quickly with minimal scarring, so the notion I had then, as a young scientist, was that if I could understand the molecules that were present in saliva, which could be anti-infectious and promote wound healing, I could make them into drugs which could be used at other sites in the body."
Dr. Malamudís earlier research in antibacterial salivary proteins led him into HIV pathogenesis and ultimately to try to design anti-HIV drugs. In 1985, while at the dental school at the University of Pennsylvania, Dr. Malamud reproduced an experiment whereby HIV-1 is incubated with saliva and loses its infectivity. HIV-1 is responsible for the vast majority of AIDS cases in the United States. Dr. Malamud and his team studied the phenomena and discovered it worked for many strains of the HIV-1 virus but not other viruses, such as herpes, adenovirus, SIV or HIV-2.
"So this meant that there was a very specific effect, and that was exciting to me as a biochemist," said Dr. Malamud. "When we found the fraction that contained the anti-HIV activity, and we purified the protein, it was a protein that I had already studied several years earlier, as an antibacterial protein. I had named it SAG, for salivary agglutinin because of what it did in the mouth. This protein, produced by the salivary glands, when it binds to bacteria, it clumps them, thus preventing the bacteria from attaching to the tooth surface and causing infection."
A second area of Dr. Malamudís research involves unique oral-based diagnostic techniques to detect bacteria and viruses using Microfluidics to automate the process of extricating biomarkers present in saliva.
"Most molecules that are in blood are also in an oral fluid sample, but their levels are much lower, 1/100 or 1/1000 of what is found in the blood," notes Dr. Malamud. ďWe use an amplification technique known as Polymerase Chain Reaction (PCR). This makes it possible to take a small amount of nucleic acid and make a lot of it by doing a series of replication cycles, thus enhancing the signal so it can be analyzed by the reader."
After a saliva sample has been amplified, it is placed in a cassette and subsequently bound to a specific capture zone and the results are analyzed by a laser in a small table-top unit in a matter of minutes.
There are numerous benefits to the oral sample over the drawing of blood.
"In the simplest case, this is generally cheaper, because you donít need a trained phlebotomist, and if I gave you the choice of rubbing a wand or getting stuck with a needle, which one would you choose?" said Dr. Malamud.
Additionally, the immediacy of the results is crucial, especially in pediatric or geriatric care. Dr. Malamudís team is working to develop what he calls point-of-care testing, whereby a child could be tested, diagnosed, and treated all in one visit.
"We want to know if itís a virus or bacteria before the child leaves the doctorís office, not in 48 hours," said Dr. Malamud. "If itís a virus, unfortunately we donít have much we could treat it with. But if itís bacteria, weíd like the tests to actually identify the bacteria, and then you know what antibiotic to prescribe.
"The plan is in two years to have a working prototype, and in five years to have a device ready for FDA approval that will be able to identify multiple viruses and bacteria. Thatís our goalÖand we're stickiní to it," said Dr. Malamud, smiling broadly.
Dr. Malamudís current funding consists of grants from the National Institutes of Health (NIH): Anti-HIV activity of lung SRCR
(gp-340) in saliva; Point detection of pathogens in oral samples via Up-converting phosphor transfer; Role of gp-340 in HIV infection and transmission; and HIV Prevention Trial Unit Microbicide Study Group. Additional grants come from New York State Office of Science, Technology and Academic Research (NYSTAR): Infectious disease: Diagnosis and Prevention; and the NYU Center for AIDS Research: Effects of HIV infection on the interactions between salivary proteins, oral microbiota, and the innate immune system.