Lisa DeLouise, Ph.D., M.P.D., associate professor of Dermatology, has received two Pilot Grants from the CTSI, each of which helped to support a line of research that blossomed into much more. She shared her experiences with CTSI Stories.
Thanks for taking the time to chat! Tell us a little about the Pilot Grants you’ve gotten through the CTSI.
The first one I got was in 2007, and it was for nanoparticle skin research. I look at cosmetic products to see if they have efficacy and any unintended toxicity issues, and back in 2006, I got involved in the question of whether nanoparticles that are increasingly formulated into various topical cosmetic products have any of these side effects.
In sunscreens, for example, there are ingredients that can have unintended biological consequences, so I was looking at a couple compounds used in sunscreens – titanium oxide and zinc oxide – which absorb UV light so your skin is protected. When these compounds were first used, they were approved by the FDA at the micron level – so, relatively speaking, the particles were too large to seep through skin.
But in the 1990s, manufacturers learned to make the metal oxide particles on the nano-scale – 1,000 times smaller. Since it was the same elemental composition, it didn’t have to go through rigorous FDA testing again, but scientists became concerned that the nano-sized particles might have different properties than the micron-level ones. Some compounds, for example, can become more optically and electrically active, or more likely to catalyze reactions that could cause oxidative stress in tissues
It seems like they might be more susceptible to being absorbed by skin.
Yes, that was also a concern – whether they could go through the skin barrier. So that’s what really launched my interest in this field of nanotoxicology, and I got some funding from the CTSI Pilot Program to look at this in the early going.
I was also questioning whether people with skin diseases – who tend to have defects in their skin barrier – could be more susceptible to penetration of these materials. So in collaboration with Lisa Beck, M.D., we made some of these comparisons.
What did you find?
Well, much of the research is still ongoing, because thanks in part to the early data gathered from the CTSI from 2007-2008, I was able to get an R01 grant in 2011. So I’m in my fourth year of that. But we do know that nanoparticles go through the skin and more easily through barrier impaired skin. The titanium dioxide has the tendency to conglomerate on the skin surface, so it loses it’s nanomaterial status. The zinc oxide, though, does get into the body, though it’s still unclear whether it’s penetrating the skin as nanoparticle or in another form such as a dissociated ions.
Very interesting. How about the second CTSI Pilot grant you received in 2011?
In 2011, the CTSI supported an application of microarray technology that allowed us to sort and enrich rare cells in the blood. The award was critical to fostering a collaboration between myself and James Kobie, Ph.D. We haven’t landed the R01 yet – we’re still trying – but the big success story is that the application of the technology has proven very positive.
In cancer, a lot of tumors are infiltrated with B-cells, which are antibody-making cells. So understanding the antibodies and other proteins secreted will help us understand the disease and why the B-cells are there sometimes and not there other times. Also, in cancer therapeutics, the field seems to be headed toward controlling the immune system and training it to fight the cancer in a more effective way.
So with the microarray technology, we were able to prove that you could look specifically at these human B-cells and their secretions. Earlier this year, we started a company named Nidus Biosciences to explore the potential of this technology. The CTSI is what really kept us going with momentum in that crucial early stage.