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David F. Katz, Nello L. Teer, Jr. Professor of Biomedical Engineering and Professor of Center for Biomolecular and Tissue Engineering
Dr. Katz's research interest include methods for prophylaxis against STD's, emphasizing topical microbicides and contraception; biofluid mechanics; rheology and transport phenomena; biophysical aspects of mammalian sperm motility, sperm transport, and fertilization; and biomechanical functioning of the vitreous of the eye.Biomedical Imaging and Image Processing. According to the Joint United Nations Programme on HIV/AIDS, 40 million people worldwide are currently living with AIDS. In 2003, 3 million people died of AIDS and 5 million new people became infected. Prevention of initial infection by HIV, as well as treatment of the AIDS disease, is critical to combating this terrible worldwide pandemic. Vaccines are one type of AIDS prevention modality, and there is much current research on them. However, this research is expected to require about another 6 - 10 years before efficacious products might become available, and there is no guarantee that successful vaccines will be developed, even in this extended time frame. An alternative prevention method is the use of topical formulations (e.g. gels, foams, etc.) that a woman inserts into her reproductive tract and which prevent HIV (or other pathogens) from initiating infection. Academic and industrial researchers are currently developing and evaluating a new class of compounds, termed topical microbicides. These compounds kill or dysfunctionalize HIV or other target pathogens upon contact in the female reproductive tract. To-date, microbicide research has been directed almost exclusively toward discovery of new, improved microbicidal compounds. There has been virtually no companion effort on rational design of the formulations which women apply and which deliver microbicides to the target pathogens. We do not yet understand what physical and chemical properties microbicidal formulations should have in order to be most effective in preventing infection. Objective standards for evaluation of such formulations do not exist. The effectiveness of microbicidal formulations depends upon their ability to coat the surfaces of the lower reproductive tract, and to remain in place during the time when a woman is exposed to HIV. Our research group is pioneering analysis of the physical and chemical mechanisms responsible for such distribution and retention of microbicidal formulations (termed deployment) and for the delivery of the microbicidal molecules to target tissues, fluids and the pathogens themselves. We also work on practical application of this knowledge in the evaluation of current candidate microbicidal formulations and in development of improved ones.
Our research on microbicidal formulation deployment and drug delivery utilizes the methods of mechanical, chemical, electrical and optical engineering and materials science. Our work integrates two types of research: (1) we are undertaking fundamental studies of the mechanisms of formulation deployment and delivery; and (2) we are imaging and analyzing the actual distributions of model formulations over the tissue surfaces of the lower reproductive tract in women. The fundamental studies have two components: theoretical analyses of fluid mechanical and other mass transport processes underlying deployment and drug delivery are linked to experimental simulations (in the laboratory) of salient flow and mass transport mechanisms. For example we developed a spectrophotometric method for analyzing microbicide diffusion from a formulation into cervical mucus. We have built experimental simulations of how gravity and the squeezing forces of vaginal epithelial surfaces cause a formulation to flow over those surfaces. We have recently built a simulation of how mixing of a microbicidal formulation with ambient in vivo fluids (e.g. vaginal fluid, semen) alters the formulation's properties and, therefore, its tendency to flow and adhere to epithelial surfaces. We also perform experimental measurements of fundamental material properties of formulations such as rheological and surface properties. These serve as inputs to the theoretical models of mass transport and flow. The mathematical models reveal particular relationships between properties of formulations and deployment and delivery characteristics.
We also measure in women the spreading and retention in the vagina of different vaginal formulations. These formulations serve as models for future microbicidal products. Our human studies are conducted in the clinic of the Department of Obstetrics and Gynecology at the Duke Medical Center. We apply a new, unique imaging instrument built by us, that shares some features with the endoscopes currently used clinically to visualize some interior regions of the body. Our instrument measures the local thickness of coating of the vaginal surfaces with a test formulation. It detects 'bare spots' of uncoated tissue that might be particularly vulnerable to infection. We plan to compare the results of our studies in the laboratory with the measurements of formulation deployment in women in the clinic. Our goal here is to begin to develop understanding and confidence in the accuracy of our laboratory methods to predict features of deployment that occur in women in the body. To the extent that our methods are accurate, they will provide a valuable, and heretofore missing tool in the efforts to design and develop better microbicidal products.
Our research is sponsored by the National Institutes of Health, the US Food and Drug Administration (FDA), the American Foundation for AIDS Research, and the CONRAD Program (funded by the US Agency for International Development and the Gates Foundation).
Teaching (Fall 2013):
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