A. Clementina Mesaros, PhD

faculty photo
Research Assistant Professor of Pharmacology
Department: Pharmacology

Contact information
421 Curie Blvd.
BRB II/III, room 856
Philadelphia, PA 19104
Office: 215-459-2116
Fax: 215-573-9889
Lab: 215-573-9886
Education:
B.Sc. (Chemistry and biochemistry)
Babes-Bolyai University, Cluj-Napoca, Romania, 1996.
MS. ( Chemistry of heterocyclic compunds)
Babes-Bolyai University, Cluj-Napoca, Romania, 1997.
Ph.D. (Bio-organic chemistry )
Department of Chemistry, Case Western Reserve University, Cleveland, OH. , 2005.
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Description of Research Expertise

The three major research interests of the Mesaros group include quantitatively understanding the pathological metabolic changes in Friedreich’s Ataxia (FA), the changes in the critical fats (called lipids) in neurodegeneration, and biomarkers of exposure and exposure-response to major pollutants.

1. Quantify and achieve a targetable understanding of how lipid metabolism is disrupted as a consequence of mitochondrial dysfunction in Friedreich’s ataxia (FA).
FA is an autosomal recessive disease caused by an intronic GAA triplet expansion in the FXN gene, leading to reduced expression of the mitochondrial protein frataxin. Interestingly, we have observed increased fatty acid oxidation in platelets from patients with FA, but lipid accumulation has been reported in other tissues. To investigate if the findings in platelets reflect a therapeutically useful homeostatic mechanism- to reduce fat accumulation as well as to circumvent reduced glycolysis, we measure changes in lipidome and metabolome in FA fibroblasts and whole blood to gain insight into the disease pathogenesis and identify potential biomarkers of FA onset, disease progression, and therapeutic intervention.

2. Quantify the “sphingo-lipidome” changes that result from complex I inhibition by pesticides.
The etiology of most neurodegenerative disorders (ND) is multifactorial and consists of an interaction between environmental factors and genetic predisposition, but there is substantial evidence linking many ND to long-term/low-dose exposure to certain classes of pesticides. Most of these pesticides share the ability to induce mitochondrial dysfunction, oxidative stress, and other factors that are likely to lead to selective cell death. It is unlikely that oxidative stress is the sole factor that links mitochondrial dysfunction with neurodegeneration; therefore, defects in mitochondrial metabolism apart from ROS production could be important to the pathogenesis of several ND. This project measures the sphingo-lipidome perturbations caused by pesticides using primary rat neurons (RPN) and will expand our current understanding of mitochondrial abnormalities that result from complex I inhibition.

3. Measure the relationship between biomarkers of exposure and biomarkers of response from major pollutants.
Biomarkers of exposure reflect the dose and timing of exposure to environmental pollutants and biomarkers of response capture the reaction of a living organism to this exposure. With new analytical chemistry approaches, understanding both of these types of biomarkers can better pinpoint the burden and mechanism of environmental contribution to disease and help untangle the complicated interaction of genetics and environment. Due to compelling preliminary evidence, we are interested in the potential involvement of toxicants in the pathological development of gestational diabetes. Recent studies show that pancreatic serotonin signaling plays a critical role in maternal glucose homeostasis. Epidemiological findings have linked PFOA exposure to maternal hyperglycemia, insulin resistance, and glucose intolerance. PFOA exposure in pregnant mice is causatively linked to gestational diabetes through mechanisms that perturb serotonin metabolism in the maternal pancreatic islets and the effects are modulated by genetic differences in vitamin B6 metabolism. We are investigating the serotonin pathway in PFOA-exposed mice to further elucidate the mode of action of this compound and identify pharmacologically relevant steps to design interventions. This project is a collaboration with Susiarjo Lab from the University of Rochester.

Description of Other Expertise

In addition to her own interests, Dr. Mesaros is the Technical Director of the Translational Biomarker Core within the Center of Excellence in Environmental Toxicology (CEET) at the University of Pennsylvania. Both her independent research and Director position entail maintaining a fleet of liquid chromatography-mass spectrometry, inductively coupled plasma-mass spectrometry, and high-resolution mass spectrometry instruments as well as training and supervising of support staff, undergraduates, graduate students, and postgraduate scientists.

Selected Publications

Fields AM, Welle K, Ho ES, Mesaros C, Susiarjo M.: Vitamin B6 deficiency disrupts serotonin signaling in pancreatic islets and induces gestational diabetes in mice. Commun Biol. 2021 Mar 26;4(1):421. doi: 10.1038/s42003-021-01900-0. Nature Publishing Group, 4(1): 421, Mar 2021.

McAndrew NP, Bottalico L, Mesaros C, Blair IA, Tsao PY, Rosado JM, Ganguly T, Song SJ, Gimotty PA, Mao JJ, DeMichele A.: Effects of systemic inflammation on relapse in early breast cancer. NPJ Breast Cancer 7: 7, Jan 2021.

Narapareddy L, Rhon-Calderon EA, Vrooman LA, Baeza J, Nguyen DK, Mesaros C, Lan Y, Garcia BA, Schultz RM, Bartolomei MS.: Sex-specific effects of in vitro fertilization on adult metabolic outcomes and hepatic transcriptome and proteome in mouse. FASEB J 35: e21523, Apr 2021.

Mazaleuskaya Liudmila L, Salamatipour Ashkan, Sarantopoulou Dimitra, Weng Liwei, FitzGerald Garret A, Blair Ian A, Mesaros Clementina: Analysis of HETEs in human whole blood by chiral UHPLC-ECAPCI/HRMS. Journal of lipid research 59(3): 564-575, 03 2018.

Lynch David R, Farmer Jennifer, Hauser Lauren, Blair Ian A, Wang Qing Qing, Mesaros Clementina, Snyder Nathaniel, Boesch Sylvia, Chin Melanie, Delatycki Martin B, Giunti Paola, Goldsberry Angela, Hoyle Chad, McBride Michael G, Nachbauer Wolfgang, O'Grady Megan, Perlman Susan, Subramony S H, Wilmot George R, Zesiewicz Theresa, Meyer Colin: Safety, pharmacodynamics, and potential benefit of omaveloxolone in Friedreich ataxia. Annals of clinical and translational neurology 6(1): 15-26, 01 2019.

Wang Siyu, Blair Ian A, Mesaros Clementina: Analytical Methods for Mass Spectrometry-Based Metabolomics Studies. Advances in experimental medicine and biology 1140: 635-647, 2019.

Rashid CS, Bansal A, Mesaros C, Bartolomei MS, Simmons RA.: Paternal bisphenol A exposure in mice impairs glucose tolerance in female offspring. Food Chem Toxicol 145: 111716, Nov 2020.

Chandramouleeswaran PM, Guha M, Shimonosono M, Whelan KA, Maekawa H, Sachdeva UM, Ruthel G, Mukherjee S, Engel N, Gonzalez MV, Garifallou J, Ohashi S, Klein-Szanto AJ, Mesaros CA, Blair IA, Pellegrino da Silva R, Hakonarson H, Noguchi E, Baur JA, Nakagawa H.: Autophagy mitigates ethanol-induced mitochondrial dysfunction and oxidative stress in esophageal keratinocytes. PLoS One 15: e0239625, Sep 2020.

Kuskovsky Rostislav, Buj Raquel, Xu Peining, Hofbauer Samuel, Doan Mary T, Jiang Helen, Bostwick Anna, Mesaros Clementina, Aird Katherine M, Snyder Nathaniel W: Simultaneous isotope dilution quantification and metabolic tracing of deoxyribonucleotides by liquid chromatography high resolution mass spectrometry. Analytical biochemistry 568: 65-72, Mar 2019.

Lee Seung-Cheol, Shestov Alexander A, Guo Lili, Zhang Qian, Roman Jeffrey C, Liu Xiaobin, Wang Hong Y, Pickup Stephen, Nath Kavindra, Lu Pin, Hofbauer Samuel, Mesaros Clementina, Wang Y Lynn, Nelson David S, Schuster Stephen J, Blair Ian A, Glickson Jerry D, Wasik Mariusz A: Metabolic Detection of Bruton's Tyrosine Kinase Inhibition in Mantle Cell Lymphoma Cells. Molecular cancer research : MCR 17(6): 1365-1377, Jun 2019.

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Last updated: 03/29/2021
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