Pipettes and Politics

The joy of teaching lies not only in helping students surpass their own expectations but in the collaborative process that makes learning a shared journey. In my approach, fostering a love for science and learning happens through meaningful collaboration—with students, colleagues, and the broader academic community. I believe that when we embrace collaboration, we empower students to actively engage with material, rediscover their scientific curiosity, and take ownership of their learning. By creating discussion-based classrooms and utilizing evidence-based pedagogies, I work alongside students to foster inquiry and critical thinking, helping them develop the skills to ask insightful questions and seek meaningful answers. Incorporating my own research into the classroom enriches this process, bringing real-world insights and cutting-edge developments into our discussions. This not only keeps students connected to the latest in the field but also demonstrates the dynamic relationship between teaching and research. Collaboration with peers further enhances my teaching by enabling me to share ideas, refine methods, and experiment with new approaches. While challenges such as administrative pressures and discipline-specific cultures can pose obstacles, our commitment to supporting one another’s growth—through both successes and setbacks—strengthens the teaching community as a whole. This collaborative mindset not only enhances student engagement and critical thinking but also fosters a deeper love for the work we do and a shared passion for teaching and learning that transforms the classroom experience. A good teacher, by necessity, is also a good researcher—constantly questioning, experimenting, and refining their approach to foster an environment of collaborative inquiry and growth.

Science is not performed in a vacuum, and scientists do not make strides without other who have helped them along the way. Throughout my career, I have been fortunate to have had many mentors who have been instrumental in my scientific journey. Now with a career in academia, I have worked hard to improve academia for scientists at all levels, especially those that have been historically marginalized. I will discuss my scientific career path through the lens of all the people that have supported, encouraged and inspired me throughout the years.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the fastest-growing etiology of hepatocellular carcinoma (HCC). This work identifies novel gene and lipid associations in human MASLD-driven HCC that may be exploited for therapeutic benefit. Methods: Human HCC tumor (n=8) and adjacent non-tumor samples (n=8) were obtained from the Biospecimen Procurement and Translational Pathology Shared Resource Facility at the University of Kentucky Markey Cancer Center. All patients met cardiometabolic MASLD criteria and were negative for viral hepatitis. Hematoxylin and eosin (H&E) staining was used for pathological determination of tumor and adjacent nontumor tissue. Lipids were extracted using a methyl-tert-butyl ether extraction method and subjected to lipidomics by the West Coast Metabolomics Center. RNA was isolated and used for bulk sequencing. Data were analyzed using paired nonparametric analyses via a Wilcoxon or Mann-Whitney test, as appropriate. Results: Histological analysis by H&E showed significant lipid vacuole accumulation in HCC tumors relative to nontumor tissue. Lipidomic analysis revealed significant increases in long-chain nonesterified monounsaturated fatty acids (MUFAs; C16:1, C18:1, C20:1) and MUFA-enriched phospholipids (PC30:1, PC32:1, PE32:1, and PC36:1) in tumors relative to nontumor tissue. No significant differences were observed in nonesterified polyunsaturated fatty acids (PUFAs; C18:2, C20:4, and C22:6), PUFA-enriched phospholipids (C36:4, C38:4, C38:6, C40:6), or in fatty acid esters of hydroxy fatty acids (FAHFAs; C38:2, C38:4, C38:6). However, both MUFA- (C14:1, C18:1) and PUFA-enriched acylcarnitines (C18:2, C18:3) were collectively reduced in human tumors. Differential analysis of RNA sequencing revealed fatty acid oxidation genes (CPT1A, CPT2, ACADL, ACADM, ACADS, HADHA) were significantly reduced in tumor versus nontumor tissue. Further, genes involved in de novo lipogenesis were largely dysregulated (e.g. no differences in SREBF1 or FASN; increases in ACLY, ACACA, and SCD1; decreases in ACSL1) in tumor versus nontumor tissue. Conclusions: These results suggest human HCC tumors exhibit a reduced capacity to undergo mitochondrial β-oxidation resulting in accumulation of free and esterified MUFAs with concomitant reductions in MUFA-carnitines. Current studies are underway to determine the mechanisms by which impairment of hepatic MUFA catabolism via FAO promotes the development of HCC in mice.

My laboratory has made major contributions to our understanding of non-canonical functions for protein kinases by discovering diverse and unanticipated biochemical activities that are performed by this protein superfamily. Protein kinases have been studied for decades and play important roles in many physiological and pathological processes. The textbook view is that these enzymes transfer phosphate from ATP to protein substrates in a process termed phosphorylation. However, my laboratory has overturned this paradigm by discovering new catalytic activities of atypical protein kinases and pseudokinases. For example, we discovered that the predicted pseduokinases SelO, SidJ and nsp12 catalyze AMPylation, polyglutamylation and mRNA capping, respectively. These results have revealed important new insights into the cellular response to oxidative stress and the pathogenic mechanisms employed by bacterial and viral pathogens. Our work on eukaryotic, prokaryotic, and viral kinases has exposed the catalytic versatility of the protein kinase fold and suggests that pseudoenzymes should be analyzed for alternative catalytic activities. In this lecture, I will present our recent discovery of kinases responsible for isoprenoid salvage.

The rationale, design, and mechanism of GABA aminotransferase and ornithine aminotransferase inactivators will be presented as well as in vitro and in vivo efficacy and pharmacokinetic results, toxicology studies, and a clinical trial with one of the inactivators.

In conversation with... Cindy Khuu by ASBMB

In conversation with... Shy Brown by ASBMB

In conversation with... Tom Kiselak by ASBMB