Research

POSTDOCTORAL RESEARCH

Upon completing her dissertation training, Katie joined the lab of Prof. William DeGrado at UC San Francisco in September 2021. Here, Katie is leveraging structural biology and de novo protein design to understand biological signal transduction mechanisms. In particular, she is focused on understanding the thermodynamic and conformational signaling of bacterial histidine kinases and two component signaling systems. 

She has presented her research at Gordon Research Conferences (Protein Engineering; Signal Transduction in Microorganisms) and Gibbs Society Conference on Biothermodynamics. She was also selected as a 2023 Leading Edge fellow, a program for gender-minority aspiring faculty. As a Leading Edge Fellow, Katie presented her research at an annual Symposum held at HHMI Janelia Research Campus. Her research is supported by an NIH Ruth Kirschstein NRSA Postdoctoral Fellowship (F32). 

DOCTORAL RESEARCH

Katie's dissertation work in the McCafferty lab focused on trafficking defects in models of Parkinson's disease and characterizing how small molecules can be used in the rescue thereof. Her primary project has focused on elucidating the mechanism of action of a small, N-arylbenzdiimidazole (NAB) ligand that alleviates phenotypic markers of α-synuclein toxicity in a manner dependent upon E3 ubiquitin ligase Nedd4 (see Tardiff et al., Science, 2013 for original identification of NAB ligand). Her efforts revealed that, despite evidence of engagement with Nedd4 in vitro, the NAB mechanism is independent of in vitro changes in Nedd4 enzymology. Rather, her work reveals a novel putative protein network involved in NAB- and Nedd4-dependent rescue of trafficking defects. This work is detailed in a first-author publication (Hatstat et al., Cell Chemical Biology, 2021). 

This work was furthered with unbiased chemoproteomic identification of targets of the NAB scaffold to further understand its mechanism of action at a molecular level. This work, completed in collaboration with the Fitzgerald lab (Duke Chemistry) revealed small GTPase Rab1a as a previously unrecognized target of NAB2 (Hatstat et al., RSC Chemical Biology, 2022, Advance Article). This enzyme has been thoroughly linked to trafficking processes disrupted α-synuclein toxicity, and her work expands our understanding of both the small molecule and druggability of proteins related to α-synuclein toxicity in Parkinson's disease. 

Her findings provided extensive opportunities in method development (Hatstat and McCafferty, Prot. Exp. Purif., 2020) and have inspired a series of additional projects that employ bioinformatic, computational, and proteomic analyses to better understand the specificity of Nedd4 at the level of protein-protein interaction driven substrate recognition (Hatstat, Pupi, and McCafferty, PLoS ONE, 2021) and in response to cellular stimuli (unpublished work). 

She has experience in a broad range of techniques within the Chemical Biology discipline, including: recombinant protein expression and purification, in vitro assay development, biophysical analyses (SPR, ITC, PTSA), mammalian tissue culture and cell-based assays, biomolecular mass spectrometry, proteomics, and small molecule synthesis and characterization. 

Katie's graduate research was supported and enabled by an NSF Graduate Research Fellowship, Bass Instructional Fellowship (Duke University), and Fellowship for Outstanding Graduate Student in Chemistry (Duke University).

UNDERGRADUATE RESEARCH

At Rhodes College, Katie worked under the guidance of Dr. Mauricio Cafiero and Dr. Larryn Peterson on an interdisciplinary study of inhibitors of the catechol-O-methyltransferase (COMT) enzyme. As COMT is involved in dopamine metabolism, Katie's work sought to identify novel catecholic and dopaminergic derivatives as inhibitors of the enzyme to prolong dopamine availability in treatment of conditions like Parkinson's. To this end, Katie conducted a density functional theory-based computational characterization of small molecule libraries (in the Cafiero lab) and synthesized those ligands for enzymatic analysis (in the Peterson lab). Katie's undergraduate research afforded three peer-reviewed publications (2 first-author, 1 second author), with all contributing authors being undergraduate researchers.

FUTURE RESEARCH INTERESTS 

Katie is interested in the features that define protein signaling pathways including protein-protein interactions, modularity, and conformational signaling. In particular, she is interested in leveraging our understand of signaling pathways to re-wire and re-purpose their components to elicit new biological outcomes. To this end, she aims to apply biophysical and structural methods with protein design and engineering to both elucidate and manipulate protein signaling events.