Clementina Mesaros, PhD

Research Associate Professor of Systems Pharmacology and Translational Therapeutics
Director, Biomolecular Mass Spectrometry Core (BMSC), Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania
Department: Systems Pharmacology and Translational Therapeutics
Contact information
421 Curie Blvd.
BRB II/III, room 856
Philadelphia, PA 19104
BRB II/III, room 856
Philadelphia, PA 19104
Office: 215-459-2116
Fax: 215-573-9889
Lab: 215-573-9886
Fax: 215-573-9889
Lab: 215-573-9886
Email:
mesaros@upenn.edu
mesaros@upenn.edu
Publications
Education:
B.Sc. (Chemistry )
Babes-Bolyai University, Cluj-Napoca, Romania, 1996.
MS. ( Chemistry of heterocyclic compunds)
Babes-Bolyai University, Cluj-Napoca, Romania, 1997.
Ph.D. (Bio-organic chemistry, Advisor: Professor Robert G Salomon)
Department of Chemistry, Case Western Reserve University, Cleveland, OH. , 2005.
Permanent linkB.Sc. (Chemistry )
Babes-Bolyai University, Cluj-Napoca, Romania, 1996.
MS. ( Chemistry of heterocyclic compunds)
Babes-Bolyai University, Cluj-Napoca, Romania, 1997.
Ph.D. (Bio-organic chemistry, Advisor: Professor Robert G Salomon)
Department of Chemistry, Case Western Reserve University, Cleveland, OH. , 2005.
Description of Research Expertise
The two major research interests of the Mesaros group include quantitatively understanding the pathological metabolic changes in Friedreich’s Ataxia (FRDA) 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 (FRDA). FRDA 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. Currently there is no approved therapy for FRDA. Individuals with FRDA exhibit neurodegeneration and hypertrophic cardiomyopathy is the cause of death in most cases. Lipid accumulation has been reported in heart tissues from FRDA patients and we quantified clear lipid accumulation in FRDA fibroblast (J Lipid Res. 2022 Sep;63(9):100255.) and in iPSC derived cardiomyocytes (CM) after FRX knock down (https://doi.org/10.1101/2022.09.27.22280432). The cardiomyopathy of FRDA exhibits distinctive pathological features, including a striking proliferation of mitochondria within the CM. In platelets from FRDA patients, decreased conversion of glucose to acetyl-CoA has been observed and is consistent with diminished pyruvate oxidation that we found in FRDA fibroblasts. 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 measured changes in the lipidome and metabolome in FRDA plasma and whole blood, to gain insights into the disease pathogenesis and identify potential biomarkers of FRDA onset, disease progression, and therapeutic intervention.
2. 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.
We are always looking for scientifically curious individuals with diverse background and expertise, to join our group!
Please email your Research Statement page(s) and your CV to mesaros@upenn.edu
Description of Other Expertise
One of Dr. Mesaros' main focus is on mentoring a new generation of rigorous analytical thinkers. Both her independent research and Core 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.Mesaros Group Members:
Dr. Qingqing Wang, Projects Manager
Dr. Jimmy Xu, Research Specialist
Dr. Gabriel Gugiu, Data Analyst
Postdoctoral Fellows:
Dr. Hennrique Taborda Riba
Undergraduate Students:
Ms. Niyati Bhandari (Upenn SAS, Junior)
NEWS:
2024 September:
We just got awarded an NIH S10 grant to acquire a new state-of-the-art LC-HRMS! Read more here:
https://reporter.nih.gov/search/4CLYEOdFpEyK9JFOhgLL-w/project-details/10854283
2024 August:
So proud of Niyati! She won the Best Poster Presentation Award by an undergraduate student at the ACS Fall meeting, in Denver, CO, for her work on chlorine exposure using a lung-on-a-chip model. Collaboration with Dr. Huh's Lab (UPENN). Read more here:
https://ceet.upenn.edu/2024/08/26/three-ceet-trainees-receive-awards-at-acs-fall-2024/
2024 August:
Excited to work with the labs of Drs. Baur and Ravinder (UPENN) on a new UO1 from NIA: Validation of NAD+ measurements for human clinical studies: multi-method inter-laboratory standardization! Read more here:
https://reporter.nih.gov/search/4CLYEOdFpEyK9JFOhgLL-w/project-details/10978752
Selected Publications
Nguyen PTT, Shiue M, Kuprasertkul N, Costa-Pinheiro P, Izzo LT, Pinheiro LV, Affronti HA, Gugiu G, Ghaisas S, Liu JY, Harris JC, Bradley CW, Seykora JT, Yang X, Kambayashi T, Mesaros C, Capell BC, Wellen KE.: Acetyl-CoA synthesis in the skin is a key determinant of systemic lipid homeostasis. Cell Rep 44: 115284, Feb 2025.Han X, Burrows M, Kim LC, Xu JP, Vostrejs W, Van Le TN, Poltorack C, Jiang Y, Cukierman E, Stanger BZ, Reiss KA, Shaffer SM, Mesaros C, Keith B, Simon MC: Cancer-associated fibroblasts maintain critical pancreatic cancer cell lipid homeostasis in the tumor microenvironment. Cell Rep. 26(43): 114972, Nov 2024.
Zhou Y, Sanchez VB, Xu P, Roule T, Flores-Mendez M, Ciesielski B, Yoo D, Teshome H, Jimenez T, Liu S, Henne M, O'Brien T, He Y, Mesaros C, Akizu N.: Altered lipid homeostasis is associated with cerebellar neurodegeneration in SNX14 deficiency. JCI Insight Apr 2024.
Iascone DM, Zhang X, Brafford P, Mesaros C, Sela Y, Hofbauer S, Zhang SL, Madhwal S, Cook K, Pivarshev P, Stanger BZ, Anderson S, Dang CV, Sehgal A.: Hypermetabolic state is associated with circadian rhythm disruption in mouse and human cancer cells. Proc Natl Acad Sci U S A 121: e2319782121, Jul 2024.
Uberoi A, Murga-Garrido SM, Bhanap P, Campbell AE, Knight SAB, Wei M, Chan A, Senay T, Tegegne S, White EK, Sutter CH, Mesaros C, Sutter TR, Grice EA.: Commensal-derived tryptophan metabolites fortify the skin barrier: Insights from a 50-species gnotobiotic model of human skin microbiome. Cell Chem Biol 32: 111-125, Jan 2025.
Turner L, Van Le TN, Cross E, Queriault C, Montana K,Trihemasava1 K, Davis J, Schaefer P, Nguyen J, Xu J, Goldspiel1 B, Hall E, Rome K, Scaglione M, Eggert J, Au-Yeung B, Wallace D, Mesaros C, Baur JA , Bailis W: Single-cell NAD(H) levels predict clonal lymphocyte expansion dynamics. Science Immunology 15(9(93)): eadj7238. March 2024.
Gupta K, Xu JP, Diamond T, de Jong IEM, Glass A, Llewellyn J, Theise ND, Waisbourd-Zinman O, Winkler JD, Behrens EM, Mesaros C, Wells RG.: Low-dose biliatresone treatment of pregnant mice causes subclinical biliary disease in their offspring: Evidence for a spectrum of neonatal injury. PLoS One 19: e0301824, Apr 2024.
Hurwitz SN, Jung SK, Kobulsky DR, Fazelinia H, Spruce LA, Pérez EB, Groen N, Mesaros C, Kurre P.: Neutral sphingomyelinase blockade enhances hematopoietic stem cell fitness through an integrated stress response. Blood 142: 1708-1723, Nov 2023.
Chen S, Paul MR, Sterner CJ, Belka GK, Wang D, Xu P, Sreekumar A, Pan TC, Pant DK, Makhlin I, DeMichele A, Mesaros C, Chodosh LA.: PAQR8 promotes breast cancer recurrence and confers resistance to multiple therapies. Breast Cancer Res 25: 1, Jan 2023.
Wang D, Ho ES, Cotticelli MG, Xu P, Napierala JS, Hauser LA, Napierala M, Himes BE, Wilson RB, Lynch DR, Mesaros C.: Skin fibroblast metabolomic profiling reveals that lipid dysfunction predicts the severity of Friedreich's ataxia. J Lipid Res 63: 100225, Jul 2022.