Mentoring of multidisciplinary global health research in tuberculosis and HIV

PROJECT SUMMARY
Dr. Brust is an infectious diseases specialist and physician-scientist at Albert Einstein College of Medicine. His
multidisciplinary patient-oriented research (POR) program focuses on the interplay of tuberculosis (TB) and
HIV in South Africa. A K24 Award would allow him to expand his POR program and develop a robust
mentoring program in TB, HIV and global health research at Einstein. Worldwide, TB is the most common
cause of death in patients with HIV, and the growing epidemic of drug-resistance threatens decades of gains in
TB prevention and care. With an emerging pipeline of novel and repurposed TB medications, there is an urgent
need for innovative research in TB pharmacology, genomics, and clinical trials to evaluate these drugs.
Similarly, there is a need to train the next generation of scientists in multidisciplinary TB/HIV and global health
POR. Dr. Brust's research program of clinical, epidemiologic, and translational studies is built upon a network
of outstanding collaborators in pharmacology, genomics, microbiology and epidemiology. He has a strong
record of successfully mentoring pre-and post-doctoral trainees from multiple institutions and using his
collaborators to provide mentees with broad technical and professional expertise. Einstein has a rich
environment for training clinical investigators through its medical school, post-doctoral fellowships and multi-
disciplinary centers (CTSA, CFAR, Global Health). Within this highly conducive training environment and with a
multi-institutional and multinational collaborative research team, Dr. Brust can expand his comprehensive
mentoring program at Einstein and internationally. His research program is unique at Einstein and his
mentorship is sought by trainees and junior investigators. His mentorship focuses on the design and execution
of hypothesis-driven research to assist mentees in becoming independent investigators. By allowing him to
decrease his clinical responsibilities, this K24 award will permit him to devote more time to mentorship and to
take on a larger number of mentees. The award will also advance his immediate and long-term career goals to:
1) Increase his knowledge of clinical pharmacology to inform current and future studies of new TB medications;
2) Understand how whole genome sequencing can reveal mechanisms of acquired TB resistance; 3) Expand
clinical trials skills to facilitate the design and implementation of TB/HIV trials for novel drugs; and 4) Enhance
the structure and content of his mentorship of trainees pursuing careers in TB/HIV and global health POR.
Finally, this award will support an innovative sub-study of Dr. Brust's new R01 to further investigate the TB
drug clofazimine: 1) To develop a novel assay to measure intracellular clofazimine concentrations; 2) To
correlate intracellular clofazimine concentrations with the emergence of bedaquiline resistance following a
treatment interruption; and 3) to compare intracellular clofazimine concentrations in alveolar macrophages with
that in PBMCs. A K24 award will provide vital protected time, enabling Dr. Brust to build upon his current
success and giving him the skills to grow as both an investigator and as a mentor.

Grant Number: 5K24AI155045-05
NIH Institute/Center: NIH
Principal Investigator: James Brust