Since arriving at the University at Buffalo in the Fall of 1992 my main role has been to conduct research. My main research focus is acute inflammatory lung injury (arising from both infectious and non-infectious causes) as it relates to the practice of critical care medicine. Gastric aspiration, bacterial pneumonia, influenza pneumonia, lung contusion, and their possible concurrency (i.e., gastric aspiration + bacterial pneumonia or lung contusion, bacterial pneumonia secondary to influenza infection, etc) are all etiologies of Acute Respiratory Distress Syndrome (ARDS) that I have investigated extensively. I have been instrumental in the development of mouse (wild type and numerous transgenic strains) and rat models (also, rabbit and sheep) of these various pulmonary insults that has facilitated the dissection of the mechanisms and perturbing factors involved in the pathogenesis of ARDS.
Of particular interest is our discovery of the greater than additive (i.e., synergistic) increase in lung injury when a gastric aspiration event includes an acidic component along with gastric food particles. Our hypothesis postulates that the combination of insults account for the disparity of outcomes that arise from aspiration events, i.e., quickly resolving pneumonitis compared to the deadly downward spiral of ARDS. These studies establish the importance of diagnostic and prognostic biomarkers that identify the specific nature of the inciting pulmonary insults and suggest potential targets for therapeutic intervention. It is hoped that the fruits of this research will be to provide critical care physicians with the tools to prevent/intervene in the progression of ARDS as opposed to relying on supportive care, the current standard of care.
Through my expertise in acute inflammatory processes I have developed several other projects in collaboration with other investigators in other, seemingly disparate areas. In establishing the requirement of acid exposure-induced cellular necrosis in the gastric aspiration-induced synergistic lung injury model we have investigated the role of damaged-associated molecular patterns (DAMPs) and an associated receptor (advanced glycation end products receptor, RAGE) in modulating the inflammatory response. Leveraging my expertise in this area, I have developed a collaboration with Dr. Tracey Ignatowski in investigating the role of DAMPs and RAGE in the development of diabetic neuropathic pain. Another example of extending my horizons has been my collaboration with Dr. John Crane. In this project I have contributed my expertise in tracking and characterizing infiltrating inflammatory cells by flow cytometry in a rabbit model of intestinal defenses against Enteropathogenic and Shiga-toxigenic Escherichia coli infection.
I am also involved in developing, in conjunction with the CDC, nanoparticle platforms for targeted nucleic acid delivery to treat influenza, as well as its most deadly complication secondary bacterial pneumonia. I continue to work with our collaborators on this project (Drs. Russo, Hakansson, Prasad, and Sambara) and have developed a quick in vitro technique for optimizing nanoplex formulations prior to in vivo testing.
I am a Research Associate Professor in UB’s Department of Anesthesiology with an adjunct appointment in the Department of Pathology and Anatomical Sciences. I have been the Department of Anesthesiology’s Basic Science Research Coordinator and now serve as its Research Director. I developed the syllabus and directed the Anesthesiology Resident Research Rotation, being involved in training residents, medical students, graduate students, post-graduate fellows, undergraduates/pre-undergrad interns, and attending faculty in the area of biomedical research. In addition, I lecture for the Department of Pharmacology and Toxicology in the area of toxic responses of the respiratory system and am a substitute instructor for the General Pathology lab.
I am the Department of Anesthesiology’s Assistant Director of its Physician Scientist Development Program that is funded by an NIH T32 Training Grant. I firmly believe that the training of physician scientists is a means for optimizing the potential for successful translational research. Adding a more scientific perspective to their education accentuates their unique point of view that allows them to identify clinical problems that are not well understood and gives them the tools to develop potential strategies to investigate them. The clinician is in an ideal position to initiate the first step of the scientific method, defining the problem. Scientific training puts them in the position of being able to investigate it.