The Reznik laboratory is focused on preterm birth. Preterm birth occurs in approximately 10% of pregnancies globally and accounts for the vast majority of perinatal morbidity and mortality. While rates of preterm birth are generally higher in developing countries, the United States has one of the highest rates of preterm birth in the world and this rate has increased in recent years. Efforts in the Reznik laboratory are directed toward the identification and development of novel agents that arrest preterm labor as well as understanding the mechanisms whereby environmental factors, such as diet, lead to increased risk of preterm birth. Several novel putative labor arresting compounds have been investigated in in vitro, ex vivo and in vivo models. We have recently discovered that a widely used drug excipient, N,N-dimethylacetamide, rescues mice from endotoxin-induced preterm birth by inhibiting nuclear factor kappa B, and are actively investigating this compound and its structural analogs as novel cytokine suppressive anti-inflammatory drugs in several systems. Another area of interest is understanding how lipotoxicity induced by consumption of a Western style high fat diet in pregnancy affects the maternal microbiome and transcriptome and, ultimately, risk of preterm birth.  We are also investigating how immune priming confers protection from inflammation-driven preterm birth. Our ultimate goal is to better understand the mechanisms leading to preterm labor and delivery in order to develop safe and effective therapies to prevent preterm birth.

Reznik SE, Salafia CM, Lage JM, Fricker LD. Immunohistochemical localization of carboxypeptidases E and D in the human placenta and umbilical cord. J Histochem Cytochem. 1998 Dec;46(12):1359-68. PubMed PMID: 9815277.

Novikova EG, Reznik SE, Varlamov O, Fricker LD. Carboxypeptidase Z is present in the regulated secretory pathway and extracellular matrix in cultured cells and in human tissues. J Biol Chem. 2000 Feb 18;275(7):4865-70. PubMed PMID: 10671522.

Ahmad Z, Reznik SE. Immunohistochemical localization of ECE-1 in the human placenta. Placenta. 2000 Mar-Apr;21(2-3):226-33. PubMed PMID: 10736246.

Novikova E, Fricker LD, Reznik SE. Metallocarboxypeptidase Z is dynamically expressed in mouse development. Mech Dev. 2001 Apr;102(1-2):259-62. PubMed PMID: 11287206.

Reznik SE, Fricker LD. Carboxypeptidases from A to z: implications in embryonic development and Wnt binding. Cell Mol Life Sci. 2001 Nov;58(12-13):1790-804. PubMed PMID: 11766880.

Koscica KL, Sylvestre G, Reznik SE. The effect of phosphoramidon on inflammation-mediated preterm delivery in a mouse model. Am J Obstet Gynecol. 2004 Feb;190(2):528-31. PubMed PMID: 14981401.

Koscica KL, Ananth CV, Placido J, Reznik SE. The effect of a matrix metalloproteinase inhibitor on inflammation-mediated preterm delivery. Am J Obstet Gynecol. 2007 Jun;196(6):551.e1-3. PubMed PMID: 17547891.

Vu TD, Yun Feng, Placido J, Reznik SE. Placental matrix metalloproteinase--1 expression is increased in labor. Reprod Sci. 2008 Apr;15(4):420-4. PubMed PMID: 18497349.

Klugman SD, Gross SJ, Liang J, Livne K, Gross B, Khabele D, Lopez-Jones M, Cordero DR, Reznik S. Expression of Keratin 8 and TNF-Related Apoptosis-I Inducing Ligand (TRAIL) in Down Syndrome Placentas. Placenta. 2008 Apr;29(4):382-4. PubMed PMID: 18343496; NIHMSID: NIHMS45734; PubMed Central PMCID: PMC2475678.

Olgun N, Patel HJ, Stephani R, Wang W, Yen H, Reznik SE. Effect of the putative novel selective ETA-receptor antagonist HJP272, a 1,3,6-trisubstituted-2-carboxy-quinol-4-one, on infection-mediated premature delivery. Can J Physiol Pharmacol. 2008 Aug;86(8):571-5. PubMed PMID: 18758506.

Wang W, Yen H, Chen CH, Soni R, Jasani N, Sylvestre G, Reznik SE. The endothelin-converting enzyme-1/endothelin-1 pathway plays a critical role in inflammation-associated premature delivery in a mouse model. Am J Pathol. 2008 Oct;173(4):1077-84. PubMed PMID: 18772340; PubMed Central PMCID: PMC2543075.

Olgun NS, Patel HJ, Stephani R, Lengyel I, Reznik SE. Blockade of endothelin-1 with a novel series of 1,3,6-trisubstituted-2-carboxy-quinol-4-ones controls infection-associated preterm birth. Am J Pathol. 2010 Oct;177(4):1929-35. PubMed PMID: 20802183; PubMed Central PMCID: PMC2947287.

Wang W, Yen H, Chen CH, Jasani N, Soni R, Koscica K, Reznik SE. Prevention of inflammation-associated preterm birth by knockdown of the endothelin-1-matrix metalloproteinase-1 pathway. Mol Med. 2010 Nov-Dec;16(11-12):505-12. PubMed PMID: 20809048; PubMed Central PMCID: PMC2972402.

Ouhilal S, Vuguin P, Cui L, Du XQ, Gelling RW, Reznik SE, Russell R, Parlow AF, Karpovsky C, Santoro N, Charron MJ. Hypoglycemia, hyperglucagonemia, and fetoplacental defects in glucagon receptor knockout mice: a role for glucagon action in pregnancy maintenance. Am J Physiol Endocrinol Metab. 2012 Mar 1;302(5):E522-31. PubMed PMID: 22167521; PubMed Central PMCID: PMC3311287.

Sundaram S, Ashby CR Jr, Pekson R, Sampat V, Sitapara R, Mantell L, Chen CH, Yen H, Abhichandani K, Munnangi S, Khadtare N, Stephani RA, Reznik SE. N,N-dimethylacetamide regulates the proinflammatory response associated with endotoxin and prevents preterm birth. Am J Pathol. 2013 Aug;183(2):422-30. PubMed PMID: 23770347; PubMed Central PMCID: PMC3730776.

Munnangi S, Gross SJ, Madankumar R, Salcedo G, Reznik SE. Pregnancy associated plasma protein-A2: a novel biomarker for Down syndrome. Placenta. 2014 Nov;35(11):900-6. PubMed PMID: 25154785; NIHMSID: NIHMS622547; PubMed Central PMCID: PMC4198481.

Adler E, Madankumar R, Rosner M, Reznik SE. Increased placental trophoblast inclusions in placenta accreta. Placenta. 2014 Dec;35(12):1075-8. PubMed PMID: 25305693.

Olgun NS, Hanna N, Reznik SE. BQ-123 prevents LPS-induced preterm birth in mice via the induction of uterine and placental IL-10. Toxicol Appl Pharmacol. 2015 Feb 1;282(3):275-84. PubMed PMID: 25230003.

Vyas V, Ashby CR Jr, Olgun NS, Sundaram S, Salami O, Munnangi S, Pekson R, Mahajan P, Reznik SE. Inhibition of sphingosine kinase prevents lipopolysaccharide-induced preterm birth and suppresses proinflammatory responses in a murine model. Am J Pathol. 2015 Mar;185(3):862-9. PubMed PMID: 25579843; PubMed Central PMCID: PMC4348465.

Pekson R, Poltoratsky V, Gorasiya S, Sundaram S, Ashby CR, Vancurova I, Reznik SE.  N,N-Dimethylacetamide significantly attenuates LPS- and TNFα-induced proinflammatory responses via inhibition of the nuclear factor kappa B pathway. Mol Med. 2016 Oct;22:747-58. PMID:  27782292.

Wang W, Yen H, Chen C-H, Soni R, Jasani N, Sylvestre G and Reznik SE.  The Endothelin Converting Enzyme-1 (ECE-1)/Endothelin-1 (ET-1) Pathway Plays a Critical Role in Infection-Associated Premature Delivery in a Mouse Model.  Am J Path 173: 1077-1084 (2008).

Wang W, Yen H, Chen C-H, Jasani N, Soni R, Koscica K and Reznik SE. Endothelin-1 and Matrix Metalloproteinase-1 Function in the Same Molecular Pathway in Infection-Associated Preterm Birth, Molec Med 16:  505-512 (2010).

Olgun NS, Stephani RA, Patel HJ and Reznik SE. Blockade of Endothelin-1 With a Novel Series of 1,3,6-Trisubstituted-2-carboxy-quinol-4-one’s Controls Infection-Associated Preterm Birth, Am J Path 177:  1929-1935 (2010).

Ouhilal S, Vuguin P, CuiL, Du X-Q, Gelling RW, Reznik SE, RussellR, Parlow AF, KarpovskyC, SantoroN and Charron MJ.  Hypoglycemia, Hyperglucagonemia and Feto-placental Defects in Glucagon Receptor Knockout Mice: A Role for Glucagon Action in Pregnancy Maintenance, Am J Phys Endo Metab 302:  E522-E531 (2012).

Sundaram S, Ashby CR, Pekson R, Sampat V, Sitapara R, Mantell L, Chen C-H, Yen H, Abhichandani K, Munnangi S, Khadtare N, Stephani RA and Reznik SE. N, N-Dimethylacetamide Regulates the Pro-inflammatory Response Associated with Endotoxin and Prevents Preterm Birth.  Am J Path 183:  422-430 (2013).

Munnangi S, Gross SJ, Madankumar R and Reznik SE.  Pregnancy Associated Plasma Protein-A2:  A Novel Biomarker for Down Syndrome.  Placenta 35: 900-906 (2014).

Adler E, Madankumar R, Rosner M and Reznik SE.  Increased Placental Trophoblast Inclusions in Placenta Accreta. Placenta 35: 7035-7038 (2014).

Olgun NS, Hanna N and Reznik SE.  BQ-123 Prevents LPS-Induced Preterm Birth Via the Induction of Uterine and Placental IL-10. Tox App Pharm 282: 275-284 (2015).

Vyas V, Ashby CR, Olgun NS, Sundaram S, Salami O, Munnangi S, Pekson R, Mahajan P and Reznik SE. Inhibition of Sphingosine Kinase Prevents Lipopolysacccharide Induced Preterm Birth and Suppresses Pro-inflammatory Responses in a Murine Model. Am J Path 185: 862-869 (2015).

Suzuki M, Maekawa R, Patterson ME, Reynolds DM, Calder BR, Reznik SE, Heo HJ, Einstein FH and Greally JM. Amnion as a Surrogate Tissue Reporter of the Effects of Preeclampsia on the Fetus. Clin Epigen 8:67 (2016).

Pekson R, Poltoratsky V, Gorasiya S, Sundaram S, Ashby CR, Vancurova I and Reznik SE. N,N-Dimethylacetamide Significantly Attenuates LPS- and TNFα-Induced Proinflammatory Responses Via Inhibition of the Nuclear Factor Kappa B Pathway. Molec Med 22: 747-758 (2016).

Manuel CR, Charron M, Ashby CR and Reznik SE. Saturated and Unsaturated Fatty Acids Differentially Regulate In Vitro and Ex Vivo Placental Anti-Oxidant   Capacity. Am J Reprod Immunol, 80:e12868 (2018) https://doi.org/10.1111/aji.12868. (Featured on journal cover.)

Reidy KJ, Hjorten RC, Simpson CL, Rosenberg AZ, Rosenblum SD, Kovesdy CP, Tylavsky FA, Myrie J, Ruiz BL, Mozhui K, Haque S, Suzuki M, Jacob J, Reznik SE, Kaskel FJ, Kopp JB, Winkler CA and Davis RL. Fetal Not Maternal apol1 Genotype Associated with Risk for Preeclampsia. Am J Hum Gen 103: 367-376 (2018).

Reznik SE, Tiwari AK and Ashby CR. Sofosbuvir: A Potential Treatment for Ebola. Front Pharm, 9: 1139 (2018).

De Vera AA, Gupta P, Lei Z, Liao D, Narayanan S, Teng Q, Chen Z-S and Reznik SE. Immuno-oncology agent IPI-549 Is a Modulator of P-glycoprotein (P-gp, MDR1, ABCB1)-Mediated Multi-drug Resistance (MDR) in Cancer: In Vitro and In vivo. Cancer Lett, 442: 91-103 (2019).

Manuel CR, Latuga MS, Ashby CR and Reznik SE. Immune Tolerance Attenuates Gut Dysbiosis, Dysregulated Uterine Gene Expression and High-Fat Diet Potentiated Preterm Birth in Mice. Am J Obstet Gynecol, 220: 596.e1-596.e28 (2019).

Patki M, Giusto K, Gorasiya S, Patel K* and Reznik SE*. 17-a-Hydroxyprogesterone Nanoemulsifying Preconcentrate Loaded Vaginal Tablet: A Novel Non-invasive Approach for the Prevention of Preterm Birth. Pharmaceutics 11: 335; doi:10.3390/pharmaceutics11070335 (2019). *Equal contributors.

Williams L, Burgos E, Vuguin P, Manuel C, Pekson R, Munnangi S, Charron M* and Reznik SE*. N-Acetylcysteine Resolves Placental Inflammatory-Vasculopathic Changes in Mice Consuming a High Fat Diet. Am J Path, 189: 2246-2257 (2019). *Equal contributors.

Gandhi T, Patki M, Kong J, Koya J, Yoganathan S, Reznik SE and Patel K. Development of Arginine Anchored Nano-globule with Retrograde Trafficking Inhibitor (Retro-2) for the Treatment of Enterohemorrhagic Escherichia Coli Outbreak. Mol Pharm 16: 4405-4415 (2019).

Giusto K, Patki M, Koya J, Ashby CR, Munnangi S, Patel K* and Reznik SE*. A Vaginal Nanoformulation of a Sphingosine Kinase Inhibitor Attenuates LPS-induced Preterm Birth in Mice. Nanomedicine, 10.2217/nnm-2019-0243, E-pub ahead of print, *Equal contributors.

Olgun SN, Morris AM, Bowers LN, Stefaniak LB, Friend SA, Kashon ML, Reznik SE and Leonard SS. Mild Steel and Stainless Steel Welding Fumes Elicit Pro-Inflammatory and Pro-Oxidant Effects in First Trimester Trophoblast Cells, Am J Reprod Immunol, in press.

For a more complete list see:

https://www.ncbi.nlm.nih.gov/myncbi/1PMpwKpFc1pAh/bibliography/public/