Assistant Professor, Environmental and Occupational Health
4131 Public Health, 130 DeSoto Street, Pittsburgh, PA 15261
Primary Phone: 967-179-5658
Web site: https://orcid.org/0000-0003-4797-7065
The primary goal of my laboratory is to develop peptide-based antimicrobial therapeutics against multidrug-resistant bacteria. A secondary objective is to establish how the environment influences the composition of the host microbiota and the resulting health consequences.
The central goal of my laboratory is to develop therapeutics with novel antimicrobial mechanisms to overcome bacterial resistance to traditional antibiotics. Antibiotic resistance constitutes a global health crisis, which threatens to reverse many advances in the field of medicine. In that regard, cationic antimicrobial peptides (AMPs) are a class of antimicrobial agents that are very promising against multidrug-resistant bacteria due to their membrane-disruption mechanisms, the lower propensity to invoke selection of resistance compared to conventional antibiotics, and bacterial killing properties that are typically not affected by the metabolic state of the bacterial cells. However, cationic peptides present several limitations related to the types of biological environments and susceptibility to protease digestion. While sequence optimization or de novo engineering can help overcome some of these limitations, AMP design is currently done mainly by trial and error based on the principle of cationic amphipathicity. Thus, the future of this promising class of peptides depends on the ability to design AMPs for specific applications by dissecting the AMP functional motifs to elucidate their differential roles in antimicrobial properties and host toxicity. This can be accomplished by establishing a general framework for cationic peptide design, based on iterative structure-function (spectrum of activity, drug affinity, bacterial killing and resistance mechanisms, and toxicity to mammalian cells) relationship to minimize peptide length required for low or absence of toxicity to mammalian cells and high therapeutic index. Data are usually streamlined to elucidate therapeutic mechanisms by dissecting the structural determinants of selectivity against MDR bacteria compared to mammalian cells.
Our approach to the microbiota in health and disease is to examine how the environment impacts host defense and inflammatory diseases based on changes in the microbiome. Environmental factors include the air (e.g., how the air microbiota contributes to the oral/lung and gut microbiome composition) or inhaled toxicants (e.g. E-cigarette vapor/other). An emerging paradigm is how environmental toxicants affect bacterial adaptation within the host. Does the virulence of opportunistic or commensal organisms change in response to environmental exposure to toxicants? However, this project is not yet initiated.
1993 City College of the University of New York, BS, Anthropology and Biochemistry
1996 City College of the University of New York, MA, Biochemistry
2006 University of Pittsburgh School of Medicine, PhD, Microbiology and Molecular Genetics
2008, University of Pittsburgh School of Medicine, MD, Medicine