Lab Members

Our Staff

Marcy Comley
M.S., Biologist
Coordinates ongoing lab efforts

Our Fellows

Mana M. Mukherjee, Ph.D.
Research Fellow

Current project: Development of next generation artificial bioorthogonal precursors to study levels and interaction partners of GlcNAc-containing glycoconjugates.

Description: Changes in GlcNAc-containing glycoconjugates are associated with a variety of human diseases, such as cancer, diabetes, and neurodegenerative diseases, however the mechanistic details linking altered glycosylation to disease pathology remain poorly understood. Recent efforts in the development of methods to study biomolecules in their native environment have unlocked the door of bioorthogonal chemistry. Functional group modifications around the sugar hydroxyl groups are tolerated by the biosynthetic pathways and transform them into the corresponding sugar-nucleotide donors. Our work is on the development of accessible and effective methods to monitor the levels and interaction partners of GlcNAc-containing glycoconjugates. N-Acetylglucosamine (GlcNAc) represents a critical link between cellular metabolism and glycoconjugates, such as O-GlcNAc and N-linked glycans, which regulate an important and ubiquitous cell signaling paradigm, as well as substrate function, localization, and stability. Our goal is to design and synthesis of easy-to-use bioorthogonal tools that can be used by any biomedical researcher to track levels and interaction partners of GlcNAc-containing glycoconjugates, and then to use them to understand their roles in human health and diseases. Our work prioritizes approaches that are simple to implement and makes use of “off-the shelf” reagents and procedures to develop and engineer bioorthogonal next-generation artificial metabolic reporters capable of specifically labeling GlcNAc-containing glycoconjugates and then applying them to pathogenic disease (metabolic dysfunction, neurodegeneration, and cancer) treatment.

Amber Lockridge, Ph.D.
PRAT Postdoctoral Fellow

Cells are able to catabolize a variety of nutrient fuels to generate energy, with carbohydrate and fatty acid oxidation being dominant drivers of ATP production in many cells outside the brain. This type of fuel flexibility is important for constitutively active tissues (e.g. the heart) or regulators of systemic metabolism (e.g. liver, adipose) to maintain optimal function despite natural fluctuations in the circulating nutrient supply. In addition, however, cells can shift their overall fuel preference in response to persistent conditions such as high fat diet, chronic stress or exercise training. Little is known about the mechanisms that drive this type of fuel shifting but fuel inflexibility has been implicated in the pathology of multiple diseases including cardiomyopathy, diabetes and non-alcoholic fatty liver disease (NAFLD). One candidate mechanism is through protein O-GlcNAcylation, which is dynamically responsive to acute nutrient levels, interactive with energy and metabolic signaling, but at a timescale that typically outlasts its triggering conditions. Mice with a genetically driven partial deletion of the O-GlcNAc removal enzyme O-GlcNAcase (OGA) demonstrate a persistent whole-body fuel shift away from fatty acid oxidation while pharmacological OGA depression delays the natural transition from carbohydrate to fatty acid fuel preference in mice moving from their fed active state to their resting and fasting state. These published data suggest that removal of O-GlcNAcylation from some protein targets may be required for the efficient utilization of fatty acid oxidation in metabolically flexible cell types. My research in the Hanover lab aims to investigate this supposition across three mechanistic hypotheses.

  1. The O-GlcNAc status of transcription factors/co-factors guide their targeting or activity at the promoters of genes that encode for lipid oxidation proteins.
  2. O-GlcNAc status influences the activity or stability of proteins that control the availability of fatty acids for oxidation.
  3. Protein O-GlcNAcylation, whether through transcriptional or direct action, manipulates carnitine homeostasis, which is critical for the mitochondrial uptake of fatty acids.

A key question of interest is whether a non-dominant splice isoform of OGA (sOGA), which has been localized at both the lipid droplet membrane and in mitochondria, might play a particularly active or lipid-sensitive role in any of these hypothesized mechanisms.

Significance/Impact – Not only will these studies expand our understanding of protein O-GlcNAcylation as a context-dependent metabolic rheostat but they may shed light on the unknown function of OGA splice regulation, which has been putatively linked to the manifestation of clinical diabetes. Furthermore, insight into the mechanisms behind adaptive fuel preference may aid in the development of therapies to mimic the metabolic benefits of exercise and fasting or to mitigate conditions of toxic lipid accumulation.

Relevant Publications - Lockridge, A & Hanover, J. A Nexus of Lipid and O-GlcNAc Metabolism in Physiology and Disease. Frontiers in Endocrinology, section Molecular and Structural Endocrinology.  Front. Endocrinol. 30 August 2022. Doi: 10.3389/fendo.2022.943576

Patricia Carvalho-cruz, Ph.D.
Visiting Fellow

O-GlcNAc modulation impacts DNA damage repair machinery in highly replicative cells

Highly replicative cells accumulate DNA mutations leading to accumulation of point mutations and chromosome abnormalities. Using mouse embryonic stem cells, mouse embryonic fibroblasts and cancer cells, Dr. Cruz aims to understand how O-GlcNAc modulation impacts replication stress, DNA damage machinery and cell fate. Dr. Cruz’s work has focused on how O-GlcNAc acts in cell plasticity and differentiation with the goal of defining metabolic and molecular O-GlcNAc targets that are involved in the response to replicative stress.

Kaylee Philbrick
Postbaccalaureate Fellow
O-GlcNAc Transferase (OGT) is a highly conserved enzyme that catalyzes the transfer of a GlcNAc sugar from UDP-GlcNAc to serine and threonine residues of its >1000 different intracellular substrates. This posttranslational modification is dynamic and can be removed by O-GlcNAcase (OGA). Disruption of the O-GlcNAc balance has been implicated in a wide variety of diseases; elevated O-GlcNAcylation has been observed in diabetes, cardiovascular disease, and cancer. These diseases are among the common conditions that put patients at increased risk of severe infectious disease, such as by COVID-19 infection, and it has been proposed that hyper-O-GlcNAcylation is partially responsible for this risk. This is supported by evidence that hyper-O-GlcNAcylation contributes to a pro-inflammatory phenotype in macrophages. While an increase in O-GlcNAcylation has been shown to be necessary for proper T-cell activation, it remains unclear if underlying hyper-O-GlcNAcylation impacts the T cell response. To better understand the impact of chronically elevated O-GlcNAc on T cell function, we activated CD4+ splenocytes harvested from mice in which OGA is specifically deleted in lymphocytes (OgaCD2-Cre) in vitro via culturing with α-CD3/CD28. Using this system, we investigated the effect of Oga-mediated hyper-O-GlcNAcylation on immunoregulatory transcription factors and cytokines at the transcriptional and translational levels. This research will give us insights into how O-GlcNAc levels modulate the immune response and have further implications in understanding inflammatory and autoimmune diseases.
Devin Biesbrock
Postbaccalaureate Fellow

Metabolites such as glucose or glucosamine get converted into their corresponding nucleotide sugar UDP-GlcNAc through the hexosamine biosynthetic pathway (HBP) or salvage pathway. These nucleotide sugars can subsequently be used for numerous post translational modifications (PTMs) such as the modification of glycans, lipids, proteins, etc. Since these monosaccharide precursors are often shared by several pathways, selectivity for or against any particular type of modification has been difficult to attain. Functional group modifications around the sugar hydroxyl groups are tolerated by the HBP, allowing for the transformation of these bioorthogonal sugars into their corresponding nucleotide-sugar donors. This provides a unique opportunity to develop and engineer artificial metabolic chemical reporters (MCRs) that allow for monitoring of the PTMs in vivo. My work involves the development of accessible and effective methods to monitor the levels and interaction partners of GlcNAc-containing glycoconjugates by interrogating the selectivity and labeling partners of these bioorthogonal sugars. The use of bioorthogonal sugars has helped increase our understanding of the cellular glycosylation of lipids and proteins, the imaging of glycans, nucleic acids and cellular organelles, the identification and tracking of active enzymes, and the mechanisms of click and release drug delivery. My project is to design and synthesize bioorthogonal artificial MCRs capable of specifically labeling GlcNAc-containing glycoconjugates and to apply them to the study of pathogenic disease (metabolic dysfunction, neurodegeneration, and cancer), as well as its treatment.

Our Alumni

Dr. William B. Jakoby, Ph.D
Scientist Emeritus
Conducted Research/Editing - Detoxication
G. Gilbert Ashwell, M.D.
Scientist Emeritus
Conducts research—Lectins and Carbohydates
Dr. Barbara-Wolff-Siniski, Ph.D.
Postdoctoral Fellow; Year Departed 1990
Current Position: Senior researcher, Novartis, Inc.
Dr. Min K. Park, Ph.D.
Postdoctoral Fellow; Year Departed 1990
Current Position: Professor, University of Tokyo.
Dr. Cristopher Starr, Ph.D.
Postdoctoral Fellow; Year Departed 1991
Current Position: Director of Research, Glycobiology, Inc.
Dr. Mara D'Onofrio, Ph.D.
Postdoctoral Fellow; Year Departed 1991
Current Position: Senior Researcher, University of Sienna.
Dr. Rolf Koenig, Ph.D.
Postdoctoral Fellow; Year Departed 1992
Current Position: Professor, University of Texas, Galveston.
Dr. Mill W. Miller, Ph.D.
Postdoctoral Fellow; Year Departed 1994
Current Position: Professor, Wright State University.
Dr. Suanne Bailer, Ph.D.
Postdoctoral Fellow; Year Departed 1995
Current Position: Professor, Head of Innovation Field Virus-based Technologies, Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB.
Dr. Frank Sapynowitz, Ph.D.
Postdoctoral Fellow; Year Departed 1997
Current Position: Research Associate Professor, Georgetown University.
Dr. David Frank, Ph.D.
Postdoctoral Fellow; Year Departed 1997
Current Position: Research Associate Professor, University of Pennsylvania.
Dr. Maria Ragano, Ph.D.
Postdoctoral Fellow; Year Departed 1998
Current Position: Researcher, University of Sienna.
Dr. Thomas Sweitzer, Ph.D.
Postdoctoral Fellow; Year Departed 1998
Current Position: Research, Merck Pharmaceuticals.
Dr. William B. Lubas, Ph.D.
Postdoctoral Fellow
Current Position: Staff Physician, FDA
Dr. Dona C. Love, Ph.D.
Postdoctoral Fellow; Year Departed 1999 as Staff Scientist, NIDDK
Current Position: Program Officer, NIAID.
Dr. Wendy Wu, Ph.D.
Postdoctoral Fellow; Year Departed 2000
Current Position: Staff, NCBI, National Library of Medicine.
Dr. Song Yu, Ph.D.
Postdoctoral Fellow; Year Departed 2001
Current Position: Director, Division of Informatics, University of Maryland.
Dr. Dae Ook Kang, Ph.D.
Postdoctoral Fellow; Year Departed 2006
Current Position: Associate Professor, Dept. of Biochemistry and Health Science, Changwon National University (DOK).
Dr. Anna Krzeslak, Ph.D.
Postdoctoral Fellow; Year Departed 2006
Current Position: Associate Professor, Dept. of Cytobiochemistry, University of Lodz.
Dr. Myung Sun Lee, Ph.D.
Postdoctoral Fellow; Year Departed 2006
Current Position: Associate Professor, Changwon National University (DOK).
Dr. Sang Hoon Shin, Ph.D.
Postdoctoral Fellow; Year Departed 2007
Current Position: Director, Research and Development Team, Gyeonggi BioCenter, Gyeonggi Institute of Science and Technology Promotion
Dr. Eun Ju Kim., Ph.D.
Postdoctoral Fellow; Year Departed 2008
Current Position: Assistant Professor, Dept. of Science Education-Chemistry Major, Daegu University.
Dr. Chithra Keembeyihetti, Ph.D.
Postdoctoral Fellow; Year Departed 2010 as Staff Scientist, Specialist NIDDK Genomics Core
Current Position: Retired.
Dr. Michelle Mondoux, Ph.D.
Postdoctoral Fellow; Year Departed 2010
Current Position: Assistant Professor, Biology Dept., College of Holy Cross.
Dr. Salil Ghosh, Ph.D.
Postdoctoral Fellow
Current Position: Staff Scientist, FDA/CBER, Laboratory of Bacterial Polysaccharide
Dr. Seung Kee Seo, Ph.D.
Postdoctoral Fellow; Year Departed 2014 as Chemical Contractor
Dr. Michelle Bond, Ph.D.
Postdoctoral Fellow; Year Departed 2014 as Staff Scientist, NIDDK
Current Position: Program Officer, NIGMS
Dr. Kate Harwood, Ph.D.
Postdoctoral Fellow; Year Departed 2017
Jhulian Alston
IRTA Postbac; Year Departed 2017
Current Position: Ph.D, Candidate, Washington University in St. Louis
Dr. Ilhan Akan, Ph.D.
Postdoctoral Fellow; Year Departed 2017 as Staff Scientist, Specialist NIDDK Genomics Core
Current Position: Reviewer, FDA.
Dr. Moriah Eustice, Ph.D.
Postdoctoral Fellow; Year Departed 2018 as Lecturer, University of Maryland University College
Current Position: Biologist, FDA.
Dr. Stephanie Olivier-Van Stichelen, Ph.D.
Postdoctoral Fellow; Year Departed 2019
Current Position: Assistant Professor, Medical College of Wisconsin.
Jeffrey Boakye
IRTA Postbac; Year Departed 2019 as Medical Student, University of Connecticut Medical School
Current Position: Medical Student, University of Connecticut Medical School.
Dr. Agata Steenackers, Ph.D.
Postdoctoral Fellow; Year Departed 2020 as Senior Research Scientist, Florida International University
Current Position: Lab Manager, Versiti Blood Center of Wisconsin.
Joshua Dowson
IRTA Postbac; Year Departed 2020 as Postbac, NIDDK, Cheung Lab
Current Position: Medical Student, Columbia University Medical School.
Dr. Mohit P. Mathew, Ph.D.
Postdoctoral Fellow; Year Departed 2021
Current Position: Scientist, Salubrious Biotherapeutics.
Meagan Dagnachew
IRTA Postbac; Year Departed 2021 as Medical Student, Georgetown Medical School
Current Position: Medical Student, Georgetown Medical School.
Dr. Hyun Jin Na, Ph.D.
Postdoctoral Fellow; Year Departed 2022 as Assistant Professor, Korean Food Research Institute
Current Position: Assistant Professor, Korean Food Research Institute
Dr. Dan Konzman
JHU Graduate Student; Year Departed 2023
Lara K. Abramowitz, Ph.D.
Staff Scientist; Year Departed 2023 as Staff Fellow, FDA
Last Reviewed March 2023