Research Interests

RESEARCH INTERESTS

The Kane laboratory’s goals include elucidating disease mechanisms towards identifying new therapeutic targets and informing on mechanism(s) of action of current drug candidates using a combination of mass spectrometry-based techniques including quantitative LC-MS/MS, targeted metabolomics, lipidomics, proteomics, and mass spectrometry imaging. For more information on any of these areas or to discuss the potential for collaboration, email Maureen at mkane@rx.umaryland.edu.

Mass Spectrometry – Method Development, Validation, Application

Interrogation of biological problems often involves the development of new analytical methodology. We have experience developing mass spectrometry-based methodology and applying existing methodology for quantitative LC-MS/MS, targeted metabolomics, lipidomics, proteomics, and mass spectrometry imaging.

Some recent work of ours in this area:

Retinoid Metabolism and Homeostasis

Through various naturally occurring metabolites, vitamin A controls essential physiological functions. The term “retinoids” describes compounds that include vitamin A (retinol), its metabolites, and synthetic analogs that exhibit vitamin A activity. Retinoic acid (RA) is an active metabolite of vitamin A and an essential regulator of cell proliferation, differentiation, apoptosis, development, nervous system function, reproduction, and the immune response. Disruption of the retinoid pathway during metabolic abnormalities, is thought to disregulate RA biosynthesis potentially affecting hundreds of genes that are directly and indirectly regulated by RA as well as rapid RA-dependent processes, such as translation.

The Kane Lab focuses on retinoid metabolism and bio-analytical chemistry with an emphasis on development of new bio-analytical technologies and their application to study retinoid metabolism and its role in disease. Overall, studies aim to identify new targets for therapeutic intervention and disease prevention through understanding of RA metabolism and how changes to RA homeostasis contribute to the aberrant physiology. This research utilizes cell systems, animal models, and human subjects using quantitative mass spectrometry of proteins and small molecules/metabolites, biochemistry and molecular biology techniques, as well as various chromatographic and spectroscopic approaches. Current research interests include:

  • Impact of cellular retinol-binding protein, type 1 (CRBPI) on development and progression of various disease states including, cancer, inflammation and fibrosis
  • Mechanisms of RA regulation during development
  • Mechanisms of RA regulation during reproduction
  • Role of retinoic acid in HIV intestinal mucosal immunity
  • Mechanisms regulating retinoic acid homeostasis
  • Development of enabling analytical technologies for retinoid quantification.
  • Therapeutic effects of retinoids

Some recent work of ours in this area:

CRBPI

Development

Reproduction

Intestinal Mucosal Immunity

Retinoid Homeostasis

Analytical Development

Therapeutic Effects of Retinoids

Bacterial Metabolism

We have an active collaboration with the Oglesby-Sherrouse and Wilks labs in the department of Pharmaceutical Sciences centered around understanding bacterial metabolism and various metabolic determinants for virulence. This work involves the Mass Spectrometry Center interfacing with the Metallotherapeutics Center

Some recent work of ours in this area:

Biomarkers

Our biomarker work involves using LC-MS/MS-based methodology as well as mass spectrometry imaging (MSI) for discovery, characterization, and validation of biomarkers to inform on a variety of exposures, injuries, and therapeutic efficacy.

Current areas of research include:

  • Radiation-induced injury
  • Ethanol exposure
  • Oxidative stress
  • Brian injury: traumatic brain injury, brain injuries during birth

Radiation biomarkers. We have worked with the medical countermeasures against radiological threat (MCART) consortium; a group that led the establishment of well-defined animal models that accurately mimic acute radiation syndrome (ARS) and the delayed effects of acute radiation exposure (DEARE) to be used for drug development under the FDA Animal Rule. Within the framework of these well-defined animal models, we have worked to identify and characterize biomarkers that accurately delineate radiation-induced injury in order to provide biomarkers that have diagnostic, prognostic, predictive, and/or pharmacodynamic utility. My laboratory’s biomarker program consists of a combination of mass spectrometry based techniques: (A) MS Profiling, (B) MALDI Mass Spectrometry Imaging, and (C) LC-MS/MS Biomarker Candidate Validation.

Ethanol exposure biomarkers. This area of research is focused on examining prenatal alcohol exposure, environmental toxicants, and therapeutic interventions. We aim to develop and quantify reliable biomarkers that will better detect an infant’s risk for neurodevelopmental delays among newborns who were affected by prenatal exposure to alcohol or other toxic substances. The significance of this work is that our findings could lead to earlier recognition of risk, which would allow for earlier interventions that could improve developmental outcomes for those children affected by these exposures.

Oxidative stress. We have several ongoing studies to characterize biomarkers of oxidative stress including a study to quantify oxidative stress biomarkers after sodium ferric gluconate administration to compare brand and generic formulations.

Brian injury: traumatic brain injury, brain injuries during birth. We have used lipidomics to identify species that could be useful as biomarkers for traumatic brain injury. We additionally are working on a hypoxia-ischemia model to use MALDI-MSI to identify species altered by hypoxia-ischemia and attenuated by hypothermia or exacerbated by existing inflammation. We additionally are interrogating lipid raft compositional changes in the hypoxia-ischemia model (using proteomics and lipidomics) and quantifying indices of oxidative stress.

Some recent work of ours in this area:

Radiation-induced injury

Ethanol-exposure biomarkers

Traumatic brain injury

Pharmaceutical Analysis

Our collaborations in the area of pharmaceutical analysis include bioanalysis for bioequivalence studies, establishing pharmacokinetic (PK) profiles for drug moieties, and development and validation of analytical methodology for accurate quantification. We generally develop and validate LC-MS/MS methods according to the FDA Guidance for Bioanalytical Method Validation. We additionally have the capability for Good Laboratory Practice (GLP) compliant operations to enable pharmaceutical analysis under GLP standards which allows us to perform bioanalysis studies used to assess safety as part of the FDA drug approval process.

Some recent work of ours in this area:

Collaborative Studies

We also work collaboratively with a number of people on various topics. If you are interested in discussing the potential for collaborating, email Maureen at mkane@rx.umaryland.edu.