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Dr. Prisic received her B.Sc. degree in Biochemistry and then Ph.D. in Biochemistry from the University of Belgrade and Iowa State University, respectively. As a graduate student, under guidance of Dr. Reuben Peters, she studied plant terpene cyclases, including structure-function relationship and enzymatic mechanisms of these enzymes. She moved to Boston Children’s Hospital / Harvard Medical School for her postdoctoral training in Microbiology. As Dr. Robert Husson’s mentee, Dr. Prisic studied pathogenesis of Mycobacterium tuberculosis, the causative agent of tuberculosis. In particular, she worked on Ser/Thr protein kinases and their targets. Since joining faculty at the University of Hawaii at Mānoa in August 2014, she has been focused on mycobacterial adaptation to zinc depletion, the host-pathogen interaction in tuberculosis, and the role of alternative ribosomes in bacteria. As a Principal Investigator, Dr. Prisic has published in high impact journals and has been awarded grants from NIH, NSF, and private foundations, including the prestigious NSF CAREER grant. In addition to being a devoted scientist, Dr. Prisic is passionate about teaching and mentoring, with special emphasis on supporting underserved and underrepresented students at early stages of their education and training.
Tuberculosis (TB) is the deadliest human pathogen, even to this day. Although antituberculars (antibiotics used to treat TB) are available, TB therapy is long and complex. The culprit is a subpopulation of Mycobacterium tuberculosis (Mtb) that resists killing by the host immune system or antibiotics. Better known as an intracellular pathogen, Mtb is also found extracellularly in necrotic lesions (granulomas). This subpopulation is notoriously difficult to eradicate during treatment and their physiology is the big unknown. We hypothesize that zinc ion (Zn2+) limitation is a “secret ingredient”- a simple environmental cue that leads to complex physiological changes in the elusive extracellular Mtb. While intracellular Mtb must cope with a Zn2+ overload, extracellular Mtb released from lysed macrophages into necrotic granulomas has a limited access to this nutrient. Zn2+ sequestration is a part of the host’s nutritional immunity, which is achieved by accumulation of neutrophil derived protein calprotectin. In contrast to many other pathogens, Mtb can overcome this severe Zn2+ depletion. In addition, Mtb can use Zn2+ depletion to signal the release into the extracellular environment and employ various protective mechanisms, including ribosome restructuring (see below). In order to understand how bacterial respond to Zn2+ limitations and their interaction with the host, Dr. Prisic’s group uses classic microbiological techniques, genetic manipulation, microscopy, in vivo and in vitro infection models, and multi-omics analysis of Mtb and other mycobacteria.
Fig. 1: Macrophages infectd with red Mtb Fig. 2: Multi-omics analysis of mycobacteria
Mtb and many other bacteria, replace Zn2+-dependent ribosomal proteins with Zn2+-independent paralogs to form alternative ribosome when zinc is limited. Therefore, bacteria may use changes in zinc availability as a signal to adjust their physiology to specific environments. In particular, morphogenic programs, including cell wall remodeling triggered by zinc depletion may allow bacteria to survive stresses imposed by their host or shifting environments, as seen in pathogenic and non-pathogenic bacteria, respectively. Dr. Prisic uses a range of methods to study those regulatory mechanisms, including proteomics, microscopy, flow cytometry, and various in vitro and in vivo phenotypic assays.
Fig. 3: Morphology of M. smegmatis lacking alternative ribosomes
*corresponding author, ^undergraduate or graduate student mentee, # equal contribution
Full list of publications and other information can be find here: https://orcid.org/0000-0003-3137-4358
Allexa Dow (PhD student)
Brandi Antonio (PhD student)
Endrei Marcantonio (PhD student)
The Prisic Lab is looking for ambitious and hardworking graduate students and postdocs. Please contact Dr. Prisic directly, if interested.
Our lab is always open for undergraduate research and training.
Both paid and volunteering opportunities may be available.
Please contact Dr. Prisic with inquiries.