VAI Epigenomics Workshop: At the Intersection of Epigenomics and Metabolomics

Stefanos Apostle has an M.S. in Cell and Molecular Biology and a B.S. in Biology from Grand Valley State University. Stefanos joined the Pospisilik Lab in 2020 and has focused on bioinformatics analysis of multi-omics high-throughput data sets to address biological heterogeneity, as well as the development of novel computational tools to aid in efficient and reproducible results.

Maxim Artyomov, Ph.D., is an Alumni Endowed Professor in the Pathology & Immunology Department at the Washington University in St.Louis. The Artyomov Lab works in the field of systems immunology, particularly focusing in the areas of immunometabolism (Nat Rev Imm, 2019) and aging (Nat Rev Imm, 2021). A key scientific approach in the Artyomov Lab is generation and analysis of high-dimensional data coupled with detailed in vitro and in vivo follow-up using classical immunology/biology approaches.

One major example of this approach is utilization of metabolic and transcriptional data integration to dissect metabolic remodeling of activated macrophages, which identified glutamine dependence of M2-polarization, metabolic breakpoint (Idh) in TCA cycle of M1-activated macrophages, rewiring toward aspartate-argininosuccinate shunt and the redirection of the metabolic flux to itaconate production (Jha et al, 2015). This systematic follow-up work led the Artyomov Lab to the discovery of anti-inflammatory action of itaconate such as mild inflammasome inhibition (Lampropoulou et al, 2016), the electrophilic properties of itaconate (Bambouskova et al, 2018) and its ability to enhance type I interferon signaling (Swain et al, 2020) and establish tolerance to late inflammasome activation (Bambouskova et al, 2021).

In a parallel effort, the Artyomov Lab applied a systems biology approach to understand the aging of the immune system in both mice and humans and defined a distinct subpopulation of age-associated GZMK+ CD8 T-cells that is dominant in old mice and is characterized by exhaustion markers (Immunity, 2021). The Artyomov Lab demonstrated some unique in vitro inflammatory properties of these age-associated CD8 T cells as well as the fact that their development depends on the aged environment. Human aging has been further detailed in their massive profiling of PBMCs from ~250 donors using a custom CYTOF panel and single-cell RNA-seq (Nat Aging, 2021a; Immunity accepted, 2023). In separate work, the Artyomov Lab provided comprehensive multiomic characterization of the aging of the classical human monocytes and defined new DNA methylation signatures of aging (Nat Aging, 2021b).

Dr. Brad Dickson received his Ph.D. in chemistry from Clemson University, where he studied enhanced sampling algorithms for molecular dynamics simulations. After studying path sampling techniques at UT Austin, in 2009 Brad began working with adaptive bias methods as a postdoctoral researcher at École Normale Supérieure de Lyon. Brad has deployed these adaptive schemes to probe kinase dynamics while at Purdue University, and to inform drug discovery efforts against epigenetic targets while working in the Center for Integrative Chemical Biology and Drug Discovery at University of North Carolina Chapel Hill. In 2015, Dr. Dickson joined the Rothbart Laboratory at Van Andel Institute (VAI), where he used computational biophysics to inform on the complex mechanics underlying chromatin accessibility, interaction and function. He is now a staff scientist at VAI.

Benjamin A. Garcia obtained his B.S. in Chemistry at UC Davis in 2000, where he worked as an undergraduate researcher in Prof. Carlito Lebrilla’s laboratory. He received his Ph.D. in Chemistry in 2005 at the University of Virginia under Prof. Donald Hunt and then was an NIH NRSA Postdoctoral Fellow at the University of Illinois under Prof. Neil Kelleher from 2005-2008. From there, Ben was appointed as an Assistant Professor in the Molecular Biology Department at Princeton University from 2008-2012, until his recruitment as the Presidential Associate Professor of Biochemistry and Biophysics at the University of Pennsylvania Perelman School of Medicine in 2012, promoted to full Professor in 2016, and named the John McCrea Dickson M.D. Presidential Professor in 2017. Ben moved in the summer of 2021 to the Washington University School of Medicine in St. Louis to become the Raymond H. Wittcoff Distinguished Professor and Head of the Department of Biochemistry and Molecular Biophysics. The Garcia lab has been developing and applying novel proteomic approaches and bioinformatics for interrogating protein modifications, especially those involved in epigenetic mechanisms such as histones during human disease, publishing over 385 publications.  He is presently an Associate Editor of the Analytical Chemistry, and Mass Spectrometry Reviews journals; and serves on the editorial boards for the Molecular Omics, the Journal of Proteome Research and the Molecular and Cellular Proteomics journals. He also serves on the Board of Directors for the U.S. Human Proteome Organization (HUPO), the HUPO Governing Council/Executive Committee and the Executive Committee of the American Chemical Society (ACS) Analytical Chemistry Division. Ben has been recognized with many honors and awards for his mass spectrometry research including the American Society for Mass Spectrometry (ASMS) Research Award, a National Science Foundation CAREER award, an NIH Director’s New Innovator Award, the Presidential Early Career Award for Scientists and Engineers (PECASE), an Alfred P. Sloan Fellowship, the PITTCON Achievement Award, the Ken Standing Award, the ACS Arthur F. Findeis Award, The Protein Society Young Investigator Award, the ASMS Biemann Medal, the HUPO Discovery in Proteomic Sciences Award, and was named a Fellow of the Royal Society of Chemistry.

Dr. Ben Johnson earned his B.S. in biology from Calvin College and his Ph.D. in microbiology and molecular genetics from Michigan State University. His graduate work focused on developing chemical probes to dissect molecular mechanisms of environmental sensing and adaptation in Mycobacterium tuberculosis (TB), with the ultimate goal of identifying new therapies against TB infections. The small molecules identified often would not directly kill TB in vitro and instead acted as anti-virulence compounds, disarming the pathogen during infection. Thus, computational biology approaches were used in conjunction with “wet” experiments to narrow down putative pathways altered in response to treatment with these experimental compounds to generate tractable hypotheses. Following graduate school, he worked as a bioinformatics research scientist in the Bioinformatics and Biostatistics Core at Van Andel Institute doing sequencing data analysis. In 2019, he joined the laboratories of Drs. Tim Triche and Hui Shen as a postdoctoral fellow and, in 2021, he transitioned fully to the Shen Lab.

Dr. Adelheid (Heidi) Lempradl is an assistant professor in Van Andel Institute’s Metabolic and Nutritional Programming group, where she investigates how the parental metabolic state is transmitted through generations. She earned her diploma and her Ph.D. from University of Vienna, where she used fluorescent probes to study the structure and folding of lipid membranes and RNAs. She continued her RNA work as a postdoctoral fellow in the lab of Dr. Leonie Ringrose at University of Austria, followed by a fellowship in the lab of Dr. Asifa Akhtar at Max Planck Institute of Immunology and Epigenetics in Freiburg, Germany. Most recently, she was a fellow in the lab of Dr. J. Andrew Pospisilik, also at Max Planck. Her research was the first to demonstrate that acute paternal diet of Drosophila can reprogram offspring metabolism. This work also identified the first epigenetic signature of obesity that is conserved across species, which established the value of Drosophila as a model for intergenerational inheritance. She was the recipient of the 2002 DOC-fFORTE Ph.D. Fellowship from the Austrian Academy of Sciences, was nominated for the Helmholtz Young Investigator Diabetes (HelDi) Award in 2018, and has given invited talks at numerous meetings and symposia, including the keynote address at the SETAC/iEOS Joint Topic Meeting on Environmental and (Eco) Toxicological Omics and Epigenetics.

Huilin Li, Ph.D., is an internationally recognized structural biologist with more than 20 years of experience in cryo-electron microscopy (cryo-EM). His current work focuses on the eukaryotic DNA replication, the mycobacterial proteasome system, and the protein folding and protein glycosylation.

Dr. Li earned his Ph.D. in electron crystallography from the University of Science and Technology Beijing, where he trained with the late Prof. K.H. Kuo. He then completed postdoctoral research in the labs of Dr. Bing Jap and Dr. Kenneth Downing at Lawrence-Berkeley National Laboratory, where he studied membrane channels and microtubule structure by cryo-EM. From there, he joined Brookhaven National Laboratory as an associate biophysicist, rising through the ranks to attain a tenured position. In 2010, he joined Stony Brook University as a professor in the Department of Biochemistry and Cell Biology while also maintaining a summer appointment at Brookhaven. He is now a professor and chair of Van Andel Institute’s Department of Structural Biology.

Zach Madaj joined the Bioinformatics and Biostatistics Core as a biostatistician in 2015. A graduate of the University of Michigan (M.S., biostatistics) and Grand Valley State University (B.S., mathematics), he brings statistical analysis, consulting, and teaching experience to the core. His focus is on study design, statistical analysis, and the development of educational resources.

Dr. Scott Rothbart is an internationally recognized expert in the field of epigenetics, particularly in the area of chromatin regulation through histone post-translational modifications. He earned a B.S. in food science and human nutrition from the University of Florida, followed by a Ph.D. in pharmacology and toxicology from Virginia Commonwealth University in the lab of Dr. Rick Moran. Dr. Rothbart then completed a postdoctoral fellowship in Dr. Brian Strahl’s lab at the University of North Carolina at Chapel Hill. He established his lab at Van Andel Institute in 2015 and was promoted to associate professor in 2018. Dr. Rothbart’s work has contributed fundamental insights into mechanisms of epigenetic regulation and has introduced new tools and methodologies to the field. He is the recipient of numerous awards and honors, including a K99/R00 career development award from the National Cancer Institute and an R35 Maximizing Investigators’ Research Award (MIRA) from the National Institute of General Medical Sciences.

Dr. Ryan Sheldon leads Van Andel Institute’s Mass Spectrometry Core, which boasts a top-tier mass spec infrastructure. Dr. Sheldon earned a B.A. in health and fitness and an M.S. in health and kinesiology from Purdue University, followed by a Ph.D. in exercise physiology from University of Missouri. He completed a postdoctoral fellowship in Biochemistry in the lab of Dr. Eric B. Taylor at University of Iowa before joining VAI in 2019 as a research scientist in the Department of Metabolism and Nutritional Programming. Dr. Sheldon was instrumental in establishing and building VAI’s metabolomics platforms. In 2020, he led the transition of the platform into VAI’s Core Technologies and Services as the Metabolomics and Bioenergetics Core, where he served as core manager. He continued to further expand the Core’s offerings and, in 2022, he led the build-out of the Core’s mass spec capabilities, resulting in a state-of-the-art service portfolio that supports innovative research at VAI and beyond. Now named the Mass Spectrometry Core, this extensive suite of technologies and expertise continues to expand its offerings under Dr. Sheldon’s leadership, with proteomic services slated to go live in 2023.

Sophie Trefely’s research interest is in the role of metabolites as signaling molecules connecting dietary nutrients to health. She established her research group at the Babraham Institute, Cambridge, UK in 2022. Her lab investigates metabolic regulation in the nucleus with the goal of understanding how nutrients affect epigenetics and how this may be manipulated for cell reprogramming.

Dr. Trefely completed her BMedSci(Hons) at UNSW, Australia in 2008 and her Ph.D. training in the lab of David James studying insulin action at the Garvan Institute of Medical Research in 2015. Her postdoctoral research at the University of Pennsylvania was jointly between the labs of Kathryn Wellen and Nathaniel Snyder and focused on the biological roles of acyl-CoA metabolism, and metabolomics. She developed rigorous approaches for subcellular metabolite analyses by mass spectrometry revealing distinct regulation of nuclei compared to other compartments. Current work in the Trefely Lab investigates the biophysical properties that define the nucleus as a metabolic compartment, metabolic pathways connecting nutrients to nuclear metabolites, and how nuclear metabolism and epigenetic change-of-state are coordinated in differentiation.

Dr. Tim Triche, Jr., earned his A.B. in chemistry from Cornell University, followed by an M.S. in biostatistics and a Ph.D. in statistical genetics from University of Southern California. Prior to joining Van Andel Institute’s Department of Epigenetics in 2017, he served as a postdoctoral fellow in the Jane Anne Nohl Division of Hematology at USC’s Norris Comprehensive Cancer Center, where he studied the roles of cellular and immune senescence in benign and malignant blood disorders, including acute myeloid leukemia and pediatric leukemia. He has been a key member of The Cancer Genome Atlas Research Network since 2011, and has contributed to more than a dozen of the consortium’s publications in journals such as Nature and Cell. As a statistician with interests in both basic and translational research, Dr. Triche’s work focuses on improving patient outcomes and quality of life through the design of randomized clinical trials, which are critical components of moving promising therapies from the lab to the doctor’s office.