Dr. Greenhouse is a physician scientist trained in internal medicine, infectious diseases, and biostatistics. His research goals are to advance the understanding of malaria epidemiology, in particular transmission dynamics and host immunity. To study the complex interplay between malaria parasites, human and mosquito hosts, and the environment, Dr. Greenhouse's work combines field, laboratory, and advanced data analysis techniques, including development of novel technological and analytical approaches. There is a large and growing interest in translational global health research among trainees, particularly clinicians. However, success in this field requires obtaining a broad skill set and lacks an established training path or the sufficient availability of appropriate mentors. Dr. Greenhouse has been highly productive in this area of patient oriented research (POR), as evidenced by his publication record and portfolio of funded research. He is dedicated to mentoring the next generation of scientists, but lacks dedicated time for mentoring or career development. In this application, Dr. Greenhouse outlines his qualifications in performing high quality POR and track record in mentoring successful trainees. He presents a plan for improving the quality and quantity of his mentoring, including formal training in mentorship, developing a structured mentorship plan, and recruiting talented trainees from a large pool of candidates, including infectious diseases fellows and clinicians from resource limited settings. He will also use protected time to build advanced skills in sequencing, bioinformatics, and population genetics. Dr. Greenhouse ultimately plans to develop a center of excellence (with the support of his division) in molecular and computational infectious disease epidemiology in order to advance interdisciplinary training and accelerate research in this area. Dr. Greenhouse's existing research portfolio provides a wealth of opportunities for trainees in 3 related areas of translational malaria research: genetic epidemiology to track malaria transmission and geographical spread, novel serologic assays of P. falciparum exposure for improved surveillance in control and elimination, and the epidemiology of P. falciparum infection and immunity. In addition, Dr. Greenhouse proposes to augment his POR with 3 novel aims to be supported by this K24 award, leveraging the highly successful East African International Center of Excellence in Malaria Research (ICEMR) study, funded by the NIH for another 6 years: 1) to develop sequencing-based platforms for comprehensive characterization of P. falciparum antigenic variation and the host antibody response; 2) to determine how antibody responses develop in response to natural P. falciparum infection, and how pre-existing and evolving responses are associated with clinical outcomes of these infections; and 3) to determine whether P. falciparum infections acquired during travel are different in terms of genetic makeup and clinical outcomes than locally acquired infections.
These aims will support his career development and mentoring objectives, and generate preliminary data for new lines of POR.
Becoming a successful translational scientist in the field of international infectious diseases is challenging, requiring extensive training in leading field studies, developing and performing laboratory assays, and synthesizing and interpreting the data generated. This K24 award will provide Dr. Greenhouse protected time for mentoring and career development, allowing him to help train the next generation of scientists in this area, drawing upon his broad expertise and established research program. He also outlines a new direction of patient oriented research, leveraging a successful collaborative research program in Uganda and advanced sequencing technologies to study the development of immunity to malaria.