Metabolism Reprogramming Lab












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            * Aims

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            We focus on interdisciplinary research of the metabolism of various cells, ranging from te

            differentiated ones to the cancer-transformed cells. We study the abilities of the cell to
            the cellular metabolism according to the availability of nutrients and their ability to em
            metabolic enzymes and their individual isoforms. The ability of the cancer cell to reprogr

            metabolism represents one of key hallmarks of carcinogenesis (Hanahan D. & Weinberg R.A., 
            646-674, 2011).


            Our aim is to understand the molecular mechanisms of pathological changes in cellular meta
            uncover the weaknesses of the cancer metabolism, which could emerge as new targets of anti
            Pathological changes in metabolism can be represented by both the causes and consequences 

            civilization diseases or heritable diseases, including various types of diabetes.





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            * Available positions
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            Potential bachelor, master and PhD students can choose from currently offered topics. We s

            creative students, who are interested to explore scientifically attractive topics under th
            experienced lab workers in a friendly atmosphere. If interested, please send your motivati
            C.V. (in case you worked previously in any lab, include also the recommendation, if possib

            of P. Heneberg [ URL "mailto:petr.heneberg@lf3.cuni.cz"] .

            • We currently offer two Ph.D. positions [ URL "https://www.lf3.cuni.cz/AKTUALITY-11786-ve

              heneberg.pdf"] .

            We annually offer SVA topics [ URL "https://www.lf3.cuni.cz/3LF-372.html#1"] to students o

            Medicine at the Third Faculty of Science.





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            * Newly opened course Precision Medicine
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            In the European ESF / ERDF project framework, we opened an undergraduate teaching laborato

            contains state-of-the-art equipment that allows experiments in molecular biology. The annu
            course for students of General Medicine from the Third Faculty of Medicine and others is o
            laboratory, where it is possible to get in touch with modern techniques of precision medic


            The course CPVL055 (Precision medicine: Practical course of biomedical research) covers a 
            of approaches ranging from bioinformatics tools, DNA and RNA isolation and analysis, recom

            preparation, measurement of effects of DNA variations in clinically important enzymes, tis
            selected analytical methods, processing of obtained results, critical interpretation of a 
            scientific publication related to the course topic, aiming to identify both reproducible a

            errors within the examined publication. We present all tasks in a clinical context so that
            in routine contact with patients is evident. The use of precision medicine becomes importa
            clinical specializations that focus on the treatment of malignancies and hereditary diseas






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            * Current focus

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            We focus on the roles of hexokinases in cancer cell metabolism. Depending on the tissue co
            cells may express multiple isoforms of hexokinases. Cancer cells mostly upregulate the exp

            of hexokinase I or hexokinase II. To study the isoform-specific roles of hexokinases, we u
            engineering techniques (CRISPR/Cas9, CRISPRi, Sleeping Beauty transposon system, lentiviru
            the biochemical and molecular-biological methods. Using these approaches, we monitor chang

            of metabolic pathways. We also extend our focus beyond metabolism towards the effects of h
            intracellular signaling pathways that are associated with the development and progression 


            The laboratory has been approved for the use of genetically modified organisms of level II
            may include (optionally) work with laboratory animals or cells of patients and volunteers.






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            * Selected publications
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            1.Heneberg, P.: Diabetes in stiff-person syndrome. Trends Endocrinol Metab. 2023; 34 (10):
              10.1016/j.tem.2023.07.005.
            2.Heneberg, P.: A large portion of diabetes cases in sub-Saharan African populations with 

              drug-induced diabetes [ URL "https://doi.org/10.1007/s00125-023-05904-9"] . Diabetologia
              1162-1164. doi: 10.1007/s00125-023-05904-9
            3.Heneberg, P. (2022): Lactic Acidosis in Patients with Solid Cancer [ URL "https://doi.or

              ars.2021.0267"] . Antioxid Redox Signal. 37 (16-18): 1130-1152.
            4.Šimčíková, D.; Gardáš, D.; Hložková, K.; Hruda, M.; Žáček, P.; Rob, L.; Heneberg, P. (20
              of hexokinase 1 sensitizes ovarian cancer to high-dose metformin [ URL "https://doi.org/

              s40170-021-00277-2"] . Cancer Metab. 9 (1): 41.
            5.Šimčíková, D.; Heneberg, P. (2019): Identification of alkaline pH optimum of human gluco
              because of ATP-mediated bias correction in outcomes of enzyme assays [ URL "https://doi.

              s41598-019-47883-1"] . Scientific Reports 9 (1): 11422.
            6.Šimčíková, D.; Heneberg, P. (2019): Refinement of evolutionary medicine predictions base
              clinical evidence for the manifestations of Mendelian diseases [ URL "https://doi.org/10

              s41598-019-54976-4"] . Scientific Reports 9 (1): 18577.
            7.Těšínský, M.; Šimčíková, D.; Heneberg, P. (2019): First evidence of changes in enzyme ki
              and stability of the glucokinase affected by somatic cancer-associated variations [ URL 

              doi.org/10.1016/j.bbapap.2018.12.008"] . Biochimica et Biophysica Acta (BBA) - Proteins 
              Proteomics 1867 (3): 213-218.
            8.Heneberg, P. (2019): Redox regulation of hexokinases [ URL "https://doi.org/10.1089/

              ars.2017.7255"] . Antioxidants & Redox Signaling 30 (3): 415-442.
            9.Heneberg, P. (2019): Comment on Mulukutla et al. Autoantibodies to the IA-2 Extracellula
              Refine the Definition of "A+" Subtypes of Ketosis-Prone Diabetes [ URL "https://doi.org/

              dc19-0022"] . Diabetes Care 42 (5): e81.
            10Heneberg, P.; Šimčíková, D.; Čecháková, M.; Rypáčková, B.; Kučera, P.; Anděl, M. (2019):
              against ZnT8 are rare in Central-European LADA patients and absent in MODY patients, inc

              positive for other autoantibodies [ URL "https://doi.org/10.1016/j.jdiacomp.2018.10.004"
              Diabetes and its Complications 33 (1): 46-52.
            11Heneberg, P.; Riegerová, K.; Říhová, A.; Šimčíková, D.; Kučera, P. (2018): Updates on th

              antigens of basophils: CD16 on basophils of patients with respiratory or insect venom al
              the rejection of CD203c and CD63 externalization decoupling by bisindolylmaleimides [ UR
              doi.org/10.1111/cea.13288"] . Clinical & Experimental Allergy 49 (1): 54-67.

            12Šimčíková, D.; Kocková, L.; Vackářová, K.; Těšínský, M.; Heneberg, P. (2017): Evidence-b
              of bioinformatics approaches to optimize methods that predict the effects of nonsynonymo
              acid substitutions in glucokinase [ URL "https://doi.org/10.1038/s41598-017-09810-0"] . 

              Reports 7 (1): 9499.
            13Gandalovičová, A.; Rosel, D.; Fernandes, M.; Veselý, P.; Heneberg, P.; Čermák, V.; Petru
              Kumar, S.; Moreno, V.S.; Brábek, J. (2017): MIGRASTATICS, the anti-metastatic and anti-i

              drugs: the promise and challenges [ URL "https://doi.org/10.1016/j.trecan.2017.04.008"] 
              Cancer 3 (6): 391-406.






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            * People – the lab is led jointly by Petr Heneberg & Daniela Šimčíková
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            * Petr Heneberg
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            • E-mail: petr.heneberg(zavinac)lf3.cuni.cz [ MAIL "petr.heneberg(zavinac)lf3.cuni.cz"]

            • ORCID: 0000-0002-0703-951X [ URL "https://orcid.org/0000-0002-0703-951X"]
            • ResearchGate: https://www.researchgate.net/profile/Petr_Heneberg [ URL "https://www.rese
              profile/Petr_Heneberg"]

            • Previous affiliations: 2008-2011 Ontario Cancer Institute, Toronto, Canada, 1999-2008 In
              Molecular Genetics of the Czech Academy of Sciences, Prague

            • Member of the Editorial Board of Diabetes Care [ URL "https://care.diabetesjournals.org/
              PLoS ONE (since 2015), and Anti-Cancer Agents in Medicinal Chemistry (since 2011)
            • Principal investigator of projects GA ČR 15-03438Y (2015-2017), AZV 15-32432A (2015-2019

              (2023-2026), GA ČR P301/12/1686 (2012-2014), IGA MZ ČR NT13663-3 (2012-2014)



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            * Daniela Šimčíková
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            • E-mail: daniela.simcikova(zavinac)gmail.com [ MAIL "daniela.simcikova(zavinac)gmail.com"
            • ORCID: 0000-0002-1227-846X
            • Previous affiliations: 06/2021-06/2023 Yale University School of Medicine, New Haven, CT

              European Molecular Biology Laboratory, Heidelberg, Germany, 2009-2013 Institute of Micro
              Czech Academy of Sciences, Prague.
            • Principal investigator of projects GA UK 1428218 (2018-2020), EMBO Short-term Fellowship





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            * Master students
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            Dominik Gardáš, Tomáš Pelikán, Vojtěch Charvát, and Robert Žak – our students present annu
            their work at the Faculty Student Conference. For example, in 2021, our students achieved 
            second places for their poster presentations, namely Vojta for his poster entitled “Membra

            xCT/SLC7A11 is an important regulator of ovarian cancer cell proliferation” and Tomáš for 
            entitled „Expression of glutaminase 1 affects mTOR signaling in the TOV-21 ovarian cancer 
            students also present their results at international conferences; e.g., in 2021, Dominik p

            Cold Spring Harbor Laboratory meeting Biology of Cancer: Microenvironment & Metastasis.



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            * Cooperation
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            • prof. Roman Zachoval (Department of Urology 3FM CU and TUH) – metabolism of clear cell r
              carcinoma
            • prof. Lukáš Rob (Department of Gynecology and Obstetrics 3FM CU and UHKV), dr. Kateřina 

              Motol, Department of Paediatric Haematology and Oncology) – metabolism of ovarian and en
            • dr. Miroslav Veith (Department of Ophthalmology 3FM CU and UHKV), dr. Jaroslava Dusová (
              Ophthalmology, UH Hradec Králové), dr. Veronika Matušková (Department of Ophthalmology, 

              Jan Němčanský (Department of Ophthalmology, UH Ostrava) – new types of autoantibodies in
              diabetic macular edema