A. Clementina Mesaros, PhD
BRB II/III, room 856
Philadelphia, PA 19104
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.
Description of Research ExpertiseMy expertise is in developing assays for metabolites involved in cellular oxidative stress and flux analysis of metabolites within intermediate metabolic pathways using stable-isotope dilution liquid chromatography mass spectrometry (LC-MS).
Some of the routine assays include quantification of biomarkers of oxidative stress including isoprostanes, 8-oxo-dGuo and mechanisms of bioactive lipid formation and signaling pathways related to environmental exposures. As opposed to simply assessing exposure based on direct quantification of the exposure itself, this approach attempts to make use of downstream consequences of exposures.
I am currently investigating 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. Increased fatty acid oxidation was found in platelets from patients with FA, but lipid accumulation has been reported in other tissues. To investigate if the findings in platelets reflect a homeostatic mechanism- to reduce fat accumulation as well as to surmount a shut-down glycolysis pathway, I will measure changes in lipidomics and metabolomics 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
Another of my long-term goals is to understand individual and population level environmental exposures to polycyclic aromatic hydrocarbons (PAH) and to predict sub-populations of never smokers at high-risk of non-small cell lung cancer (NSCLC). Using sophisticated metabolomics methodology I will evaluate the relationship between levels of environmental PAHs in NSCLC in life long never-smokers and determine if they correlate with changes in metabolomic biomarkers using a case control study design. This would be the first such study using a US population from an urban area. We will take advantage of an existing archival non-smoker NSCLC clinical specimens and healthy controls with matched age and gender, to quantify a mixture of PAH metabolites concomitant with metabolomics data. Positive correlations may lead to assays to predict lung cancer risk in non-smokers, or response to treatment.
Description of Other ExpertiseDay-to-day operation of a mass spectrometry facility core that includes high sensitivity instruments for exact quantification of low abundance biomarekrs but also high resolution instruments for untargeted discovery of new bio-markers, together with an inductively coupled plasma mass spectrometre for metal ions measurements. This includes also training and supervising the technical support staff and graduate and postgraduate students and ensuring adequate quality control.
Selected PublicationsUribe-Herranz Mireia, Rafail Stavros, Beghi Silvia, Gil-de-Gómez Luis, Verginadis Ioannis, Bittinger Kyle, Pustylnikov Sergey, Pierini Stefano, Perales-Linares Renzo, Blair Ian A, Mesaros Clementina A, Snyder Nathaniel W, Bushman Frederic, Koumenis Constantinos, Facciabene Andrea: Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response. The Journal of clinical investigation 130(1): 466-479, Jan 2020.
Lee Vivian, Gober Michael D, Bashir Hasan, O'Day Conor, Blair Ian A, Mesaros Clementina, Weng Liwei, Huang Andrew, Chen Aaron, Tang Rachel, Anagnos Vince, Li JiLon, Roling Sophie, Sagaityte Emilija, Wang Andrew, Lin Chenyan, Yeh Christopher, Atillasoy Cem, Marshall Christine, Dentchev Tzvete, Ridky Todd, Seykora John T: Voriconazole enhances UV-induced DNA damage by inhibiting catalase and promoting oxidative stress. Experimental dermatology 29(1): 29-38, Sep 2019.
Penn Courtney A, Chan Jessica, Mesaros Clementina, Snyder Nathaniel W, Rader Daniel J, Sammel Mary D, Dokras Anuja: Association of serum androgens and coronary artery calcium scores in women. Fertility and sterility 112(3): 586-593, Sep 2019.
Weng Liwei, Wang Qingqing, Yu Sixiang, Yang Xiaolu, Lynch David R, Mesaros Clementina, Blair Ian A: Evaluation of antibodies for western blot analysis of frataxin protein isoforms. Journal of immunological methods Jul 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.
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.
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.
Mauras Nelly, Torres-Santiago Lournaris, Santen Richard, Mericq Veronica, Ross Judith, Colon-Otero Gerardo, Damaso Ligeia, Hossain Jobayer, Wang Qingqing, Mesaros Clementina, Blair Ian A: Impact of route of administration on genotoxic oestrogens concentrations using oral vs transdermal oestradiol in girls with Turner syndrome. Clinical endocrinology 90(1): 155-161, 01 2019.
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.
Jackson Daniel, Huang Meng, Fernando Harshica, Ansari Ghulam, Howarth Marilyn, Mesaros Clementina, Penning Trevor, Elferink Cornelis: Using Precision Environmental Health Principles in Risk Evaluation and Communication of the Deepwater Horizon Oil Spill. New solutions : a journal of environmental and occupational health policy : NS 28(4): 599-616, 02 2019.