Department of Human Epigenetics

Head:

Monika Puzianowska-Kuźnicka, MD, PhD,  phone +48 22 6086591

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Secretary:

Agnieszka Włodarczyk, phone/fax. +48 22 6086410

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Research staff:

Edward Franek, MD, PhD, phone +48 22 5081405, +48 22 6086591, This email address is being protected from spambots. You need JavaScript enabled to view it.

Alina Kuryłowicz, MD, PhD, phone +48 22 6086406, This email address is being protected from spambots. You need JavaScript enabled to view it.

Monika Slupecka-Ziemilska, PhD, phone 22 6086401, This email address is being protected from spambots. You need JavaScript enabled to view it.

Marta Cąkała-Jakimowicz, PhD, phone +48 22 60 86 406, This email address is being protected from spambots. You need JavaScript enabled to view it.

Anna Domaszewska-Szostek, PhD, phone +48 22 6086404, This email address is being protected from spambots. You need JavaScript enabled to view it.

Marta Jonas, MD, PhD, phone +48 22 6086406, This email address is being protected from spambots. You need JavaScript enabled to view it.

Paulina Kołodziej, MSc,  phone +48 22 6086404, This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Technical staff:

Joanna Borkowska, MSc, phone +48 22 6086404, This email address is being protected from spambots. You need JavaScript enabled to view it.

Olga Buyanovskaya, MSc, phone +48 22 60 86 410, This email address is being protected from spambots. You need JavaScript enabled to view it.

Małgorzata Szwed, phone +48 22 60 86 406, This email address is being protected from spambots. You need JavaScript enabled to view it.

Barbara Buczek, phone +48 22 60 86 410, This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Scientific interest:

  • Phenotypes of aging. Extreme longevity.
  • Genetics and epigenetics of extreme longevity.
  • Epigenetics of skin aging.
  • Genetics and epigenetics of obesity.
  • Age-related diseases: obesity, type 2 diabetes, osteoporosis. Type 1 diabetes.

 

Grants:

  • Epigenetic regulation of estrogen metabolism in adipose tissue of obese individuals, grant no. 2018/31/B/NZ5/01556, National Science Centre, 07.2019 – 06.2021, leader: Alina Kuryłowicz, MD, PhD
  • “A randomized, open-label, two-arm clinical trial comparing the effectiveness of: 1. azithromycin + standard of care treatment regimen with standard of care treatment regimen in hospitalized patients diagnosed with mild SARS-CoV-2 infection (MEWS 0-2 points) and 2. azithromycin + standard of care treatment regimen with azithromycin + tocilizumab + standard of care treatment regimen in hospitalized patients diagnosed with mild/severe to severe SARS-CoV-2 infection (MEWS ≥ 3 points)”, grant no. grant nr 2020/ABM/COVID19/0009, Medical Research Agency, 05.2020 – 11.2021, leader: Edward Franek, MD, PhD

 

Collaboration:

  • International Institute of Molecular and Cell Biology, Warsaw, Poland.
  • Department of Geriatrics and Gerontology, Medical Centre of Postgraduate Education, Warsaw, Poland.
  • Department of Internal Medicine, Endocrinology, and Diabetology, MSWiA Central Hospital, Warsaw, Poland.
  • Department of Anesthesiology, University of Pennsylvania, Philadelphia, PA, USA.
  • Institut für Mikrobiologie und Hygiene, Charité – Universittätsmedizin Berlin, Berlin, Germany.
  • Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

 

Equipment:

Equipment for molecular biology, biochemistry, and cell culture.

 

Selected publications:

  • Hamann L, Szwed M, Mossakowska M, Chudek J, Puzianowska-Kuznicka M. First evidence for STING SNP R293Q being protective regarding obesity-associated cardiovascular disease in age-advanced subjects - a cohort study. Immun Ageing. 2020;17:7. DOI:10.1186/s12979-020-00176-y.
  • Kuryłowicz A, Cakała-Jakimowicz M, Puzianowska-Kuźnicka M. Targeting abdominal obesity and its complications with dietary phytoestrogens. Nutrients. 2020;12:582. DOI: 10.3390/nu12020582.
  • Borkowska J, Domaszewska-Szostek A, Kołodziej P, Wicik Z, Połosak J, Buyanovskaya O, Charzewski L, Stańczyk M, Noszczyk B, Puzianowska-Kuznicka M. Alterations in 5hmC level and genomic distribution in aging-related epigenetic drift in human adipose stem. Epigenomics. 2020;12:423-437. DOI:10.2217/epi-2019-0131.
  • Puzianowska-Kuznicka M, Kuryłowicz A, Walkiewicz D, Borkowska J, Owczarz M, Olszanecka-Glinianowicz M, Wieczorowska-Tobis K, Skalska A, Szybalska A, Mossakowska M. Obesity paradox in Caucasian seniors: results of the PolSenior study. J Nutr Health Ageing. 2019;23:796-804. DOI: 10.1007/s12603-019-1257-z.
  • Jonas M, Kurylowicz A, Bartoszewicz Z,  Lisik W, Jonas M, Kozniewski K, Puzianowska-Kuznicka M. Vitamin D receptor gene expression in adipose tissue of obese individuals is regulated by miRNAs and correlates with pro-inflammatory cytokines level. Int J Mol Sci. 2019;20(21):5272. DOI: 10.3390/ijms20215272.
  • Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Riesmeyer JS, Riddle MC, Rydén L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I, Cushman WC, Franek E, Hancu N, Hanefeld M, Holt S, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Cardona Munoz EG, Pirags V, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T; REWIND Investigators. Dulaglutide and  cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomized placebo-controlled trial. Lancet. 2019;394:121-130. DOI: 10.1016/S0140-6736(19)31149-3.
  • Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, Probstfield J, Botros FT, Riddle MC, Rydén L, Xavier D, Atisso CM, Dyal L, Hall S, Rao-Melacini P, Wong G, Avezum A, Basile J, Chung N, Conget I, Cushman WC, Franek E, Hancu N, Hanefeld M, Holt S, Jansky P, Keltai M, Lanas F, Leiter LA, Lopez-Jaramillo P, Cardona Munoz EG, Pirags V, Pogosova N, Raubenheimer PJ, Shaw JE, Sheu WH, Temelkova-Kurktschiev T; REWIND Investigators. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial. Lancet. 2019;394:131-138. DOI: 10.1016/S0140-6736(19)31150-X.
  • Pratley RE, Emerson SS, Franek E, Gilbert MP, Marso SP, McGuire DK, Pieber TR, Zinman B, Hansen CT, Hansen MV, Mark T, Moses AC, Buse JB; DEVOTE Study Group. Cardiovascular safety and lower severe hypoglycaemia of insulin degludec versus insulin glargine U100 in patients with type 2 diabetes aged 65 years or older: results from DEVOTE (DEVOTE 7). Diabetes Obes Metab. 2019;21:1625-1633. DOI: 10.1111/dom.13699.
  • Olczak E, Kuryłowicz A, Wicik Z, Kolodziej P, Cakala-Jakimowicz M, Buyanovskaya O, Slusarczyk P, Mossakowska M, Puzianowska-Kuznicka M. Glucocorticoid receptor (NR3C1) gene polymorphisms are associated with age and blood parameters in Polish Caucasian nonagenarians and centenarians. Exp Gerontol. 2019;116:20-24. DOI: 10.1016/j.exger.2018.12.006.
  • Walicka M, Jozwiak J, Rzeszotarski J, Zonenberg A, Masierek M, Bijos P, Franek E. Diagnostic accuracy of glycated haemoglobin and average glucose values in type 2 diabetes mellitus treated with premixed Insulin. Diabetes Ther. 2019;10:587-596. DOI: 10.1007/s13300-019-0570-1.
  • Hamann L, Ruiz-Moreno JS, Szwed M, Mossakowska M, Lundvall L, Schumann RR, Opitz B, Puzianowska-Kuznicka M. STING SNP R293Q is associated with a decreased risk of aging-related diseases. Gerontology. 2019;65:145-154. DOI: 10.1159/000492972.
  • Gilbert MP, Bain SC, Franek E, Jodar-Gimeno E, Naucck MA, Pratley R, Roginski R, Kerr Saraiva JF, Rasmussen S, Buse JB. Effect of liraglutide on cardiovascular outcomes in elderly patients: A post-hoc analysis of a randomized controlled trial. Ann Int Med. 2019;170:423-426. DOI: 10.7326/M18-1569.
  • Danne T, Cariou B, Banks P, Brandle M, Brath H, Franek E, Kushner JA, Lapuerta P, McGuire DK, Peters AL, Sawhney S, Strumph P. HbA(1c) and hypoglycemia reductions at 24 and 52 weeks with sotagliflozin in combination with insulin in adults with type 1 diabetes: the European inTandem2 Study. Diabetes Care. 2018;41:1981-1990. DOI: 10.2337/dc18-0342.
  • Laudanski K, Zawadka M, Polosak J, Modi J, DiMeglio M, Gutsche J, Szeto WY, Puzianowska-Kuznicka M. Acquired immunological imbalance after surgery with cardiopulmonary bypass due to epigenetic over-activation of PU.1/M-CSF. J Transl Med. 2018;16:143. DOI: 10.1186/s12967-018-1518-3.
  • Ruiz-Moreno J, Hamann L, Jin L, Sander L, Puzianowska-Kuznicka M, Cambier J, Witzenrath M, Schumann R, Suttorp N, Opitz B. The cGAS/STING pathway detects Streptococcus pneumoniae but appears dispensable for anti-pneumococcal defense in mice and humans. Infect Immun. 2018;86. pii: e00849-17. DOI: 10.1128/IAI.00849-17.
  • Hadar A, Milanesi E, Walczak M, Puzianowska-Kuznicka M, Kuźnicki J, Squassina A, Niola P, Chillotti C, Attems J, Gozes I, Gurwitz D. SIRT1, miR-132 and miR-212 link human longevity to Alzheimer’s Disease. Scientific Rep. 2018;8:8465. DOI: 10.1038/s41598-018-26547-6.
  • Sulicka J, Pac A, Puzianowska-Kuznicka M, Zdrojewski T, Chudek J, Tobiasz-Adamczyk B, Mossakowska M, Skalska A, Więcek A, Grodzicki T. Health status of older cancer survivors—results of the PolSenior study. J Cancer Surv. 2018;12:326-333. DOI: 10.1007/s11764-017-0672-6.
  • Mathieu C, Bode BW, Franek E, Philis-Tsimikas A, Rose L, Graungaard T, Birk Østerskov A, Russell-Jones D. Efficacy and safety of fast-acting insulin aspart in comparison with insulin aspart in type 1 diabetes (onset 1): a 52-week, randomized, treat-to-target, phase 3 trial. Diabetes Obes Metab. 2018;20:1148-1155. DOI: 10.1111/dom.13205.
  • Ruiz-Moreno J, Hamann L, Shah JA, Verbon A, Mockenhaupt FP, Puzianowska-Kuznicka M, Naujoks J, Sander LE, Witzenrath M, Cambier JC, Suttorp N, Schumann RR, Jin L, Hawn TR, Opitz B, CAPNETZ Study Group. The common HAQ STING variant impairs cGAS-dependent antibacterial responses and is associated with susceptibility to Legionnaires' disease in humans. PLOS Pathogenes. 2018;14:e1006829. DOI: 10.1371/journal.ppat.1006829.
  • Kuryłowicz A, Wicik Z, Owczarz M, Jonas MI, Kotlarek M, Świerniak M, Lisik W, Jonas M, Noszczyk B, Puzianowska-Kuznicka M. NGS reveals molecular pathways affected by obesity and weight loss-related changes in miRNA levels in adipose tissue. Int J Mol Sci. 2017;19. pii: E66. DOI: 10.3390/ijms19010066.
  • Jonas MI, Kurylowicz A, Bartoszewicz Z, Lisik W, Jonas M, Domieniek-Karlowicz J, Puzianowska-Kuznicka M. Adiponectin/resistin interplay in serum and in adipose tissue of obese and normal-weight individuals. Diabet Metab Syndrome. 2017;9:95. DOI: 10.1186/s13098-017-0293-2.
  • Owczarz M, Budzinska M, Domaszewska-Szostek M, Borkowska J, Polosak J, Gewartowska M, Slusarczyk M, Puzianowska-Kuznicka M. miR-34a and miR-9 are overexpressed and SIRT genes are downregulated in peripheral blood mononuclear cells of aging humans. Exp Biol Med. 2017;242:1453-1461. DOI: 10.1177/1535370217720884.
  • Russell-Jones D, Bode BW, De Block C, Franek E, Heller SR, Mathieu C, Philis-Tsimikas A, Rose L, Woo VC, Østerskov AB, Graungaard T, Bergenstal RM. Fast-acting insulin aspart improves glycemic control in basal-bolus treatment for type 1 diabetes: results of a 26-week multicenter, active-controlled, treat-to-target, randomized, parallel-group trial (onset 1). Diabetes Care. 2017;40:943-950. DOI: 10.2337/dc16-1771.
  • Lapko N, Zawadka M, Polosak J, Worthen GS, Danet-Desnoyers G, Puzianowska-Kuznicka M, Laudanski K. Long-term monocyte dysfunction after sepsis in humanized mice is related to persisted activation of Macrophage-Colony Stimulation Factor (M-CSF) and demethylation of PU.1, and it can be reversed by blocking M-CSF in vitro or by transplanting naïve autologous stem cells in vivo. Front Immunol. 2017;8:401. DOI: 10.3389/fimmu.2017.00401.
  • Hirsch IB, Franek E, Mersebach H, Bardtrum L, Hermansen K. Safety and efficacy of insulin degludec/insulin aspart with bolus mealtime insulin aspart compared with standard basal-bolus treatment in people with type 1 diabetes: 1-year results from a randomized clinical trial (BOOST® T1). Diabet Med. 2017;34:167-173. DOI: 10.1111/dme.13068.
  • Budzinska M, Pawlik-Pachucka E, Owczarz M, Roszkowska-Gancarz M, Slusarczyk P, Puzianowska-Kuznicka M. miR-96 and miR-145 expression increases, and IGF-1R and FOXO1 expression decreases in peripheral blood mononuclear cells of successfully aging humans. BMC Geriatrics. 2016;16:200. DOI: 10.1186/s12877-016-0379-y.
  • Puzianowska-Kuznicka M, Owczarz M, Wieczorowska-Tobis K, Nadrowski P, Chudek J, Slusarczyk P, Skalska A, Jonas M, Franek E, Mossakowska M. Interleukin-6 and C-reactive protein, successful aging, and mortality: the PolSenior study. Immun Ageing. 2016;13:21. DOI: 10.1186/s12979-016-0076-x.
  • Kumar A, Franek E, Wise J, Niemeyer M, Mersebach H, Simó R. Efficacy and safety of once-daily insulin Degludec/insulin Aspart versus insulin Glargine (U100) for 52 weeks in insulin-naïve patients with type 2 diabetes: a randomized  controlled trial. PLoS ONE. 2016;11:e0163350. DOI: 10.1371/journal.pone.0163350.
  • Kurylowicz A, Owczarz M, Polosak J, Jonas M, Lisik W, Jonas M, Chmura A, Puzianowska-Kuznicka M. SIRT1 and SIRT7 expression in adipose tissues of obese and normal-weight individuals is regulated by microRNAs but not by methylation status. Int J Obes. 2016;40:1635-1642. DOI: 10.1038/ijo.2016.131.
  • Gajewska J, Kuryłowicz A, Mierzejewska E, Ambroszkiewicz J, Chełchowska M,  Weker H, Puzianowska-Kuźnicka M. Complementary effects of genetic variations in LEPR on body composition and soluble leptin receptor concentration after 3-month lifestyle intervention in prepubertal obese children. Nutrients. 2016;8:328. DOI: 10.3390/nu8060328.
  • Bergenstal RM, Lunt H, Franek E, Travert F, Mou J, Qu Y, Antalis CJ, Hartman ML, Rosilio M, Jacober SJ, Bastyr EJ 3rd; IMAGINE 3 Trial Investigators. A randomized, double-blind clinical trial comparing basal insulin Peglispro and insulin Glargine, in combination with prandial insulin Lispro, in patients with type 1 diabetes: IMAGINE 3. Diabetes Obes Metab. 2016;18:1081-1088. DOI: 10.1111/dom.12698.
  • Petrie JR, Marso SP, Bain SC, Franek E, Jacob S, Masmiquel L, Leiter LA, Haluzik M, Satman I, Omar M, Shestakova M, Van Gaal L, Mann JF, Baeres FM, Zinman B, Poulter NR; LEADER investigators. LEADER-4: blood pressure control in patients with type 2 diabetes and high cardiovascular risk: baseline data from the LEADER randomized trial. J Hypertens. 2016;34:1140-1150. DOI: 10.1097/HJH.0000000000000890.
  • Hamann L, Bustami J, Iakoubov L, Szwed M, Mossakowska M, Schumann RR, Puzianowska-Kuznicka M. TLR-6 SNP P249S is associated with healthy aging in nonsmoking Eastern European Caucasians - a cohort study. Immun Ageing. 2016;13:7. DOI: 10.1186/s12979-016-0062-3.
  • Puzianowska-Kuznicka M, Walicka M, Osinska B, Rutkowski D, Gozdowski D, Czech M, Durlik M, Franek E. In-hospital mortality in a 4-year cohort study of 3,093,254 operations in seniors. World J Surg. 2016;40:1068-1074. DOI: 10.1007/s00268-015-3400-2.
  • Gajewska J, Kuryłowicz A, Ambroszkiewicz J, Mierzejewska E, Chełchowska M, Szamotulska K, Weker H, Puzianowska-Kuźnicka M. ADIPOQ -11377C>G polymorphism increases risk of adipokine abnormalities and child obesity regardless of dietary intake. J Pediatr Gastroenterol Nutr. 2016;62:122-129. DOI: 10.1097/MPG.0000000000000900.
  • Franek E, Haluzík M, Canecki Varžić S, Sargin M, Macura S, Zacho J, Christiansen JS. Twice-daily insulin degludec/insulin aspart provides superior fasting plasma glucose control and a reduced rate of hypoglycaemia compared with biphasic insulin aspart 30 in insulin-naïve adults with type 2 diabetes. Diabet Med. 2016;33:497-505. DOI: 10.1111/dme.12982.
  • Kurylowicz A, Jonas M, Lisik W, Jonas M, Wicik ZA, Wierzbicki Z, Chmura A, Puzianowska-Kuznicka M. Obesity is associated with a decrease in expression but not with the hypermethylation of thermogenesis-related genes in adipose tissues. J Transl Med. 2015;13:31. DOI: 10.1186/s12967-015-0395-2.
  • Iakoubov L, Mossakowska M, Szwed M, Puzianowska-Kuznicka M. A common copy number variation polymorphism in the CNTNAP2 gene: sexual dimorphism in association with healthy aging and disease. Gerontology. 2015;61:24-31. DOI: 10.1159/000363320.
  • Roszkowska-Gancarz M, Jonas M, Owczarz M, Kurylowicz A, Polosak J, Franek E, Slusarczyk P, Mossakowska M, Puzianowska-Kuznicka M. Age-related changes of leptin and leptin receptor variants in healthy elderly and long-lived adults. Geriatr Gerontol Int. 2015;15:365-371. DOI: 10.1111/ggi.12267.
  • Mossakowska M, Broczek K, Wieczorowska-Tobis K, Klich-Raczka A, Jonas M, Pawlik-Pachucka E, Safranow K, Kuznicki J, Puzianowska-Kuznicka M. Cognitive performance and functional status are the major factors predicting survival of centenarians in Poland. J Gerontol A Biol Sci Med Sci. 2014;69:1269-1275. DOI: 10.1093/gerona/glu003.
  • Iakoubov L, Mossakowska M, Szwed M, Duan Z, Sesti F, Puzianowska-Kuznicka M. A common copy number variation (CNV) polymorphism in the CNTNAP4 gene: association with aging in females. PLoS ONE. 2013;8:e79790. DOI: 10.1371/journal.pone.0079790.
  • Franek E, Osinska B, Czech M, Figat J. Mortality after surgery in Europe. Lancet. 2013;381:369-370. DOI: 10.1016/S0140-6736(13)60161-0.
  • Al-Haggar M, Madej-Pilarczyk A, Kozlowski L, Bujnicki JM, Yahia S, Abdel-Hadi D, Shams A, Ahmad N, Hamed S, Puzianowska-Kuznicka M. A novel homozygous p.Arg527Leu LMNA mutation in two unrelated Egyptian families causes overlapping mandibuloacral dysplasia and progeria syndrome. Eur J Hum Genet. 2012;20:1134-1140. DOI: 10.1038/ejhg.2012.77.
  • Puzianowska-Kuznicka M. ESR1 in myocardial infarction. Clin Chim Acta. 2012;413:81-87. DOI: 10.1016/j.cca.2011.10.028.
  • Polosak J, Kurylowicz A, Roszkowska-Gancarz M, Owczarz M, Puzianowska-Kuznicka M. Aging is accompanied by a progressive decrease of expression of the WRN gene in human blood mononuclear cells. J Gerontol A Biol Sci Med Sci. 2011;66:19-25. DOI: 10.1093/gerona/glq162.