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Nick Pokorzynski, PhD

Postdoctoral Associate
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About

Titles

Postdoctoral Associate

Biography

I received my undergraduate degree in Biochemistry from Michigan State University, where I worked in the laboratory of Dr. Christoph Benning studying lipid biosynthesis in the green algae Chlamydomonas reinhardtii. I completed my Ph.D. training in the laboratory of Dr. Rey Carabeo studying novel mechanisms of gene regulation in the obligately intracellular bacterium, Chlamydia trachomatis, during which I was awarded an F31 training grant through NIAID. This experience cultivated my continued interest in how pathogens sense and respond to their environment, particularly during infection. I therefore chose to pursue a postdoctoral position at the Yale School of Medicine in the laboratory of Dr. Eduardo Groisman studying how the model bacterial pathogen Salmonella governs central metabolic functions during nutritional stress conditions relevant to infection. In my spare time, I enjoy reading, hiking and exploring dog parks with my canine companions.

Appointments

Other Departments & Organizations

Education & Training

PhD
Washington State University, Molecular Biosciences (2020)
BSc
Michigan State University, Biochemistry, Molecular Biology/Biotechnology (2013)

Research

Overview

During my PhD training in the laboratory of Dr. Rey Carabeo, I developed a model for how the obligate intracellular bacterial pathogen, Chlamydia trachomatis, integrates its response to the deprivation two essential nutrients, iron and tryptophan. We demonstrated that C. trachomatis regulates the expression of their tryptophan salvage pathway in a unique manner through a novel iron-dependent transcription factor, YtgR. C. trachomatis salvage tryptophan from the precursor indole, provided by the microflora of the female lower genital tract. This environment is also notoriously iron-limited. Thus, YtgR regulation of tryptophan salvage ties the availability of indole to the level of iron in the environment, presumably enabling the proliferation of the pathogen. Interestingly, YtgR is regulated not only by iron levels, but also by proteolytic cleavage from an N-terminal permease domain. We observed that this domain was enriched for tryptophan codons, and contained a rare motif of three sequential tryptophan codons (WWW). Our subsequent work demonstrated that YtgR levels were regulated in a tryptophan-dependent manner via the WWW motif, conferring an attenuation-like effect to the expression of the tryptophan salvage pathway. Thus, the WWW motif completes a regulatory feedback loop, linking YtgR abundance to the availability of tryptophan, the biosynthesis of which it regulates. Chlamydia therefore appears to have evolved an exceedingly unique strategy to moderate the expression of the tryptophan salvage pathway, which likely reflects the unique environment they have adapted to in the female lower genital tract.

After defending my thesis, I continued in the Carabeo lab as a postdoctoral associate where I compared the chlamydial and host cell transcriptional response to nutritional stress to identify instances of host-pathogen conflict during persistent infections. We demonstrated that a nutritionally-stressed infected host cell is not necessarily compromised in its ability to control an infection. In fact, we found that nutrient-starved host cells can deploy alternative, secondary nutritional stresses to further limit pathogen growth. Both the primary nutritional stress and the secondary host amplification of anti-bacterial stress work synergistically to control the infection. Thus, the response of the pathogen to a given nutritional stress is the combined result of both the primary insult and the response of the host cell to the same insult.

My postdoctoral appointment in the laboratory of Dr. Eduardo Groisman at the Yale School of Medicine is focused on how Salmonella enterica coordinates central metabolic demands with the adverse nutritional conditions associated with infection. When Salmonella infects a mammalian cell, it is starved of essential nutrients, and this signal(s) induces virulence programs. Both the nutritional stress and the induction of virulence slow Salmonella growth. How does this alter the metabolism of an intracellular pathogen, and what regulates this process? We aim to elucidate the metabolic prioritization that takes place during infection to uncover new determinants of bacterial virulence.

Research at a Glance

Yale Co-Authors

Frequent collaborators of Nick Pokorzynski's published research.

Publications

2024

2023

2022

2020

2019

2017

Academic Achievements & Community Involvement

  • activity

    eLife Community Ambassador

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    Frontiers in Cellular and Infection Microbiology

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    Postdoctoral Associate

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    Postdoctoral Research Associate

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    Frontiers in Immunology

Get In Touch

Contacts

Mailing Address

Groisman Lab

Boyer Center for Molecular Medicine, 295 Congress Ave BCMM 341-343

New Haven, Connecticut 06519

United States