We congratulate Geordan Stukey on successfully defending his PhD dissertation at Rutgers University on March 18, 2025! His research has provided groundbreaking insights into lipid metabolism, particularly focusing on the regulation of phosphatidic acid phosphatase (Pah1) in Saccharomyces cerevisiae and its inhibition by the antidepressant drug sertraline.
Here’s how Professor George Carman, his thesis advisor, introduced Geordan:
“On August 19th, 2019 I received an email from Geordan Stukey. It read “Good morning Dr. Carman, my name is Geordan Stukey. If you recognize my last name, it’s because both my parents (Joseph Stukey and Virginia McDonough) worked as postdocs under you.” Yes, Ginny and Joe, who are here today, were important members of my lab. They came to my lab with glowing recommendations from their doctor mentor Dr. Charles Martin, who is a member of Geordan’s dissertation committee.
In the email, Geordan went on to ask if I knew anyone looking to hire a research technician, and of course, knowing that Ginny and Joe were his parents, I immediately answered his inquiry telling him I was interested in hiring him. Within a short time, it was clear that Geordan’s career had to advance beyond being a lab technician, and I, with the help of his parents, convinced him to apply for admission to the graduate school here at Rutgers.
It is now with great pride that I introduce Geordan for his Ph.D. defense seminar. In my 45 years at Rutgers University, he is the finest doctoral student I have mentored. Geordan's consistent excellence stems from a remarkable combination of scientific qualities: intellectual curiosity, dedication, a thirst for knowledge, ambition, strong organizational skills, excellent interpersonal abilities, attention to detail, superb writing and presentation skills, perseverance, and problem-solving ability.
You will hear this morning that his research explores the structure-function, enzymology, and molecular genetics of the Saccharomyces cerevisiae Pah1 PA phosphatase, the enzyme catalyzing the penultimate step in triacylglycerol synthesis. His key contributions include the biochemical and physiological relevance of the enzyme's catalytic core, identifying the novel RP (regulation of phosphorylation) domain, and discovery that the antidepressant sertraline is a novel inhibitor of PA phosphatase activity.
Geordan’s work demonstrates his expertise in molecular genetics, protein purification and characterization, radioactive and non-radioactive enzyme assays in examining protein kinase and lipid phosphatase activities, and protein-protein and protein-lipid interaction studies. The significance of his research is underscored by the numerous lipid-based diseases linked to Pah1’s loss or misregulation. His work has significantly advanced our understanding of Pah1 function and regulation, attributes needed to ultimately ameliorate PA phosphatase-associated diseases.
Geordan has co-authored seven refereed publications, with at least several more manuscripts in preparation. He has presented his work at numerous national and local conferences and has received awards for some of these presentations. Moreover, Geordan demonstrates leadership and provides mentorship to undergraduate research students. Always cheerful, respectful, and admired by his peers. Without further delay, I introduce Geordan Stukey.”
Dr. Stukey’s dissertation, "Structural Determinants of Yeast Phosphatidate Phosphatase Activity and Regulation: Inhibition by the Antidepressant Sertraline," advances our understanding of how lipid homeostasis is maintained in cells and reveals a previously unknown link between a common antidepressant and lipid metabolism. His findings have potential implications for microbiology and human health, particularly in treating metabolic disorders and antifungal drug development. Besides his advisor, his committee members were: Judith Storch, Charles Martin, Eric Klein and Gil-Soo Han.
Key Findings of Dr. Stukey’s Research
The Role of Pah1 in Lipid Metabolism
Pah1 is a phosphatidate phosphatase (PAP) enzyme that regulates lipid balance by converting phosphatidic acid (PA) into diacylglycerol (DAG), a key branch point intermediate for the synthesis of both membrane phospholipids and a crucial step in the synthesis of storage lipid triacylglycerol (TAG).
There is intricate regulation of PAP activity, localization, and stability through phosphorylation and dephosphorylation. This post-translational modification is crucial for the enzyme's function and its response to cellular cues.
The yeast Nem1-Spo7 complex is a key regulator of Pah1. This endoplasmic reticulum (ER)-associated phosphatase dephosphorylates Pah1, enabling its membrane association and activation for PA dephosphorylation. Mutations affecting this complex or its interaction with Pah1 lead to various cellular defects.
The RP domain is evolutionarily conversed in fungal Pah1 homologs. An RP deletion mutation resulted in a reduction in Pah1 phosphorylation, increased membrane association, and PA phosphatase activity but reduced cellular abundance.
Dysregulation of Pah1 leads to abnormal lipid storage, impaired cell growth, and metabolic disorders, such as lipodystrophy, diabetes, and inflammation.
Discovery of Sertraline as a Novel Pah1 Inhibitor
Dr. Stukey discovered that sertraline (Zoloft), a widely prescribed antidepressant, is a novel inhibitor of Pah1.
Sertraline inhibits Pah1activity through a non-competitive mechanism, interacting with an allosteric site rather than the enzyme’s active site.
It also inhibits human lipin 1a, 1b and 1g isoforms, the mammalian homologs of Pah1, suggesting potential biomedical applications.
The inhibitory effects of sertraline are stronger than those of propranolol, a well-known PAP inhibitor.
Potential Implications for Medicine and Antifungal Strategies
Given its ability to inhibit both yeast and human PAP enzymes, sertraline could be repurposed as an antifungal agent.
Since Pah1/lipin 1 activity is linked to metabolic disorders, sertraline or its derivatives could serve as therapeutic agents for lipid-related diseases.
His research suggests new drug targets for insulin resistance and obesity by modulating lipid metabolism through PAP inhibition.
A Legacy of Scientific Excellence
Beyond his dissertation research, Dr. Stukey has been an exceptional mentor, educator, and researcher:
Published multiple peer-reviewed papers, including in The Journal of Lipid Research.
Received prestigious research awards, including the George M. and Maureen D. Carman Prize in Lipids.
Presented at major scientific conferences, including the Rutgers Microbiology Symposium, Theobald Smith Society Spring Symposium, and DiscoverBMB.
Mentored undergraduate students, fostering the next generation of scientists.
His work stands at the intersection of microbiology, biochemistry, and biomedical research, bridging fundamental science with real-world applications.
For details, see Geordan's CV attached below.
We are incredibly proud of Geordan’s achievements and can’t wait to see where his career takes him next. His innovative research has already expanded the frontiers of lipid metabolism, and we look forward to his future discoveries!
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