The Protein Lipidation Conference: Enzymology, Signaling, and Therapeutics

James Hougland is an Associate Professor in the Department of Chemistry at Syracuse University. He holds adjunct appointments in the Department of Biology at Syracuse University and the Department of Biochemistry and Molecular Biology at the State University of New York (SUNY) Upstate Medical University. 

Research in Hougland’s laboratory explores the chemistry and biology of protein post-translational modification. Modifications are linked to multiple human diseases such as diabetes, obesity, cancer, and cardiovascular disease. Drawing from chemistry, biochemistry, and molecular biology, his research group investigates enzymes involved in post-translational modification to define how these enzymes and the modifications they perform control biological activity by altering protein structure, function, and localization. Focusing on enzymes involved in protein lipidation, his research examines how these enzymes recognize their substrates and catalyze reactions. His work also assesses the impact of the resulting hydrophobic modification(s) on protein function. Understanding how these enzymes select and modify protein targets will help identify novel substrates while potentially illuminating new targets for therapeutic intervention and inhibitor development.

Hougland is originally from Rock Island, Illinois. He attended Northwestern University as an undergraduate, majoring in Chemistry and Integrated Science. He pursued graduate studies in the Chemistry department at the University of Chicago, where he held a McCormick graduate fellowship and participated in the NIH Predoctoral Training Program in Chemistry & Biology. His doctoral research focused on studies of metal ion coordination and hydrogen bonds involved in catalysis of phosphoryl transfer reactions during RNA splicing by RNA-based enzymes (ribozymes). Hougland was awarded an NIH Postdoctoral Fellowship to support his research with Carol Fierke at the University of Michigan where he investigated the molecular interactions responsible for substrate specificity in protein farnesyltransferase (FTase). He joined the Chemistry Department at Syracuse University in 2010.

Dr. Mei Wang is an Associate Professor of Cancer and Stem Cell Biology a the Duke-NUS Medical School Singapore. She also holds a joint Associate Professor position in the Department of Biochemistry at the National University of Singapore. Her research laboratory’s broad interests include the investigation of molecular mechanisms of tumorigenesis and tumor progression, and novel ways of targeting cancer-specific processes. Active research areas in her lab are: (1) Protein prenylation processing, with an emphasis on isoprenylcysteine carboxylmethylation by ICMT, and its impact on tumor initiation cells, the process of metastasis and drug resistance. The focus of the studies is on identifying prenylation substrate proteins that plays regulatory role in these disease processes, and the impact of prenylation modification on the functions of these proteins. (2) Novel cancer therapy and biomarker development focusing on targeting the protein prenylation processing, especially the last enzyme isoprenylcysteine carboxylmethyltransferase (ICMT). (3) The impact of ICMT on cancer cell respiration and metabolism and ICMT impact on these functions when manipulated. This focus is based on the understanding that cancer cells have distinct metabolic needs, hence vulnerabilities compared to normal cells to changes in mitochondria respiration and anabolic/catabolic balances. Specifically, the studies focus on cell signaling events in cancer cells under the nutritional and energetic stress, which leads to catabolic activities such as autophagy, cell cycle arrest, and cell death. 

Paul Jenkins is a neuroscientist with expertise in the biology of the formation and organization of plasma membrane subdomains. His laboratory focuses on the ankyrin family of cytoplasmic scaffolding proteins, which tether many membrane proteins to the underlying actin cytoskeleton. He discovered that a large splice variant of ankyrin-G, a product of the Ank3 gene, is responsible for the formation of the axon initial segment and nodes of Ranvier, critical sites of clustered voltage-gated sodium channels that are important for normal neuronal signaling (Jenkins, et al. PNAS 112(4):957). In addition, Jenkins found that this variant was necessary for the formation of a subset of inhibitory connections in the cortex and hippocampus (Tseng, Jenkins et al. PNAS 112(4):1214), defects that are strongly associated with bipolar disorder. Mutations in ankyrin-G have been associated with bipolar disorder and schizophrenia. His laboratory studies the mechanisms by which these mutations can cause diseases, with special attention to the role of ankyrin-G palmitoylation on its N-terminus for its normal function. The recent reports on the important role of palmitoylacyltransferase modification of ankyrin-G in association with mood disorders in large-scale genetic screens suggest that regulation of ankyrin-G lipidation may have implications for this and other human diseases.