Research

When I started my research life, I didn’t have HIV in mind at all. For my postdoctoral research, I was trying to determine the structure of a small protein in the human immune system. This was in the heyday of protein structure determination. Back then it made a good high quality paper to examine a protein at the atomic level — where is this carbon, where is that hydrogen, where is this amino acid in relation to that amino acid in the protein?

HIV is a virus that interacts with the surface of human immune system cells. One of the proteins that the virus uses to get into these cells to cause the infection is a “chemokine receptor.” Under normal conditions, this receptor binds proteins (ligands called chemokines) to cause signals inside the cell. But in the case of HIV infection, HIV uses the chemokine receptor as an anchor to attach to the cell surface. When our protein binds, HIV can't bind and get in.

Based on increasing knowledge about how HIV infects cells, we hypothesized that certain combinations of proteins that either bind to HIV or bind to the cell surface could result in an extremely potent inhibitor. As I explained before, the inhibitor basically blocks HIV as it goes about trying to get into the cell. So we combined a chemokine, from the protein family I originally worked with, with a peptide that binds to HIV.

It turns out that the covalent linkage of these two inhibitors results in an inhibitor much more potent that either of them by themselves. So we ended up with an extremely potent inhibitor, even though the original base units were already considered very potent and big news when they came out. 

Our protein can’t be eaten as a pill because your stomach would digest it. So these proteins are generally considered good for putting in a cream or gel (sometimes called a microbicide) and preventing the sexual spread of HIV. So you would put it on before intercourse to stop HIV in a sexual setting. 

The next step would be animal studies. To test HIV inhibitors, we need animals susceptible to HIV, and there aren’t very many of these. We could use macaques, a type of monkey, or we could put human immune cells into mice for testing. But this is not something we can do at UC Merced. Not that many people in the country do these really advanced animal studies, and they’re expensive. 

When you go to biomedical conferences, this seems to be the common assumption, because the infection rate is so high there. Apparently, there are real issues about condom use in developing countries, even more so than here. They say if you even suggest using a condom, your partner might fly into a furious rage. So ideally our product would be a gel you could insert, like a contraceptive cream, or combined with a contraceptive cream or something useful against other diseases, where your partner wouldn’t even know you were using it.

Unfortunately, there’s not much money to be made in microbicides, although some drug companies are working on them. They tell us over and over that it should be cheaper than a condom, that it should never be more than a dollar a dose, so we do basic research but this may never see the light of day.

People have HIV all over our country too, but no, I haven’t been Africa. It would shut me down for weeks to see that. One study I read said that more than half the pregnant women of a certain age in a South African clinic were HIV infected. It’s stunning to me to hear about such high levels of infection. We know pretty cheaply how to stop the baby from getting infected, but still, the baby really might be an orphan soon. In America, we have the money and drugs to keep their mothers alive for decades, but not in South Africa.

My mom’s a nurse, and she likes to think I am going to cure AIDS. But what you always want to ask yourself is, will this really ever work on real people? Will it have an impact? You wish you could have an impact, but you know many people are working on these issues, and only a few will end up with something in clinical use, and you have to be resigned to that. Our really powerful HIV inhibitor may never end up touching anybody except for me and my lab mates.