Miklos Sahin-Toth, MD, PhD

Adjunct Professor, Molecular & Cell Biology

Miklos Sahin-Toth
617.358.3790
75 E. Newton St Evans Building

Biography

Expertise in the role of proteases in pancreatitis. Our laboratory studies how various proteases and their inhibitors in the pancreas contribute to the pathogenesis of pancreatitis. Pancreatitis is believed to occur due to inappropriate, intrapancreatic activation of digestive enzymes (e.g. trypsin, chymotrypsin, elastase), which are normally synthesized and stored in their inactive forms in the pancreas. Our long-term objectives are to understand the molecular mechanisms of human pancreatitis, using genetically determined pancreatitis (e.g. hereditary pancreatitis) as a biochemical model. The main focus of our research program is to provide biochemical evidence that genetic alterations in the three human trypsinogen isoforms (PRSS1, PRSS2 and PRSS3 genes) and the pancreatic secretory trypsin inhibitor (SPINK1 gene) can significantly influence the susceptibility for the development of pancreatitis. Thus, gain-of-function mutations in cationic trypsinogen can cause pancreatitis, while loss of function mutations in anionic trypsinogen can actually protect against pancreatitis. Loss of the inhibitory function of SPINK1 either due to mutations or to degradation by mesotrypsin can represent another risk factor for pancreatitis onset. The following specific projects are studied. (1) The role of human mesotrypsin in pancreatitis. Mesotrypsin is a unique protease specialized for the degradation of trypsin inhibitors. Premature mesotrypsinogen activation might lower protective SPINK1 levels in the pancreas and contribute to the pathogenesis of pancreatitis. (2) Characterization of pancreatitis-associated cationic trypsinogen (PRSS1) mutants. Identification of novel mutation-dependent biochemical defects that lead to hereditary pancreatitis (3) Functional analysis of anionic trypsinogen (PRSS2) mutants that afford protection against pancreatitis. The concept that loss-of-function trypsinogen mutations can protect against pancreatitis provides independent evidence for the central role of trypsin in this disease. (4) Identification of the disease-causing biochemical defects in pancreatitis-associated SPINK1 mutants.

Other Positions

  • Research Associate Professor, Biochemistry & Cell Biology, Boston University Chobanian & Avedisian School of Medicine
  • Director, Center for Exocrine Disorders, Boston University Henry M. Goldman School of Dental Medicine
  • Graduate Faculty (Primary Mentor of Grad Students), Boston University Chobanian & Avedisian School of Medicine, Graduate Medical Sciences

Education

  • Semmelweis University, MD
  • Semmelweis University, PhD

Publications

  • Published on 8/1/2018

    Jancsó Z, Hegyi E, Sahin-Tóth M. Chymotrypsin Reduces the Severity of Secretagogue-Induced Pancreatitis in Mice. Gastroenterology. 2018 10; 155(4):1017-1021. PMID: 30076839.

    Read at: PubMed
  • Published on 7/25/2018

    Hegyi E, Sahin-Tóth M. Human CPA1 mutation causes digestive enzyme misfolding and chronic pancreatitis in mice. Gut. 2019 02; 68(2):301-312. PMID: 30045879.

    Read at: PubMed
  • Published on 1/4/2018

    Párniczky A, Abu-El-Haija M, Husain S, Lowe M, Oracz G, Sahin-Tóth M, Szabó FK, Uc A, Wilschanski M, Witt H, Czakó L, Grammatikopoulos T, Rasmussen IC, Sutton R, Hegyi P. EPC/HPSG evidence-based guidelines for the management of pediatric pancreatitis. Pancreatology. 2018 Mar; 18(2):146-160. PMID: 29398347.

    Read at: PubMed
  • Published on 12/1/2017

    Németh BC, Szücs Á, Hegyi P, Sahin-Tóth M. Novel PRSS1 Mutation p.P17T Validates Pathogenic Relevance of CTRC-Mediated Processing of the Trypsinogen Activation Peptide in Chronic Pancreatitis. Am J Gastroenterol. 2017 12; 112(12):1896-1898. PMID: 29215622.

    Read at: PubMed
  • Published on 12/1/2017

    Sahin-Tóth M. Partial and complete SPINK1 deficiency cause distinct pancreatic phenotypes. Hum Mutat. 2017 12; 38(12):1619. PMID: 29091332.

    Read at: PubMed
  • Published on 10/31/2017

    Sahin-Tóth M, Hegyi P. Smoking and Drinking Synergize in Pancreatitis: Multiple Hits on Multiple Targets. Gastroenterology. 2017 12; 153(6):1479-1481. PMID: 29100845.

    Read at: PubMed
  • Published on 9/14/2017

    Márta K, Szabó AN, Pécsi D, Varjú P, Bajor J, Gódi S, Sarlós P, Mikó A, Szemes K, Papp M, Tornai T, Vincze Á, Márton Z, Vincze PA, Lankó E, Szentesi A, Molnár T, Hágendorn R, Faluhelyi N, Battyáni I, Kelemen D, Papp R, Miseta A, Verzár Z, Lerch MM, Neoptolemos JP, Sahin-Tóth M, Petersen OH, Hegyi P. High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial. BMJ Open. 2017 Sep 14; 7(9):e015874. PMID: 28912191.

    Read at: PubMed
  • Published on 9/1/2017

    Sahin-Tóth M. Genetic risk in chronic pancreatitis: the misfolding-dependent pathway. Curr Opin Gastroenterol. 2017 Sep; 33(5):390-395. PMID: 28650851.

    Read at: PubMed
  • Published on 7/28/2017

    Rosendahl J, Kirsten H, Hegyi E, Kovacs P, Weiss FU, Laumen H, Lichtner P, Ruffert C, Chen JM, Masson E, Beer S, Zimmer C, Seltsam K, Algül H, Bühler F, Bruno MJ, Bugert P, Burkhardt R, Cavestro GM, Cichoz-Lach H, Farré A, Frank J, Gambaro G, Gimpfl S, Grallert H, Griesmann H, Grützmann R, Hellerbrand C, Hegyi P, Hollenbach M, Iordache S, Jurkowska G, Keim V, Kiefer F, Krug S, Landt O, Leo MD, Lerch MM, Lévy P, Löffler M, Löhr M, Ludwig M, Macek M, Malats N, Malecka-Panas E, Malerba G, Mann K, Mayerle J, Mohr S, Te Morsche RHM, Motyka M, Mueller S, Müller T, Nöthen MM, Pedrazzoli S, Pereira SP, Peters A, Pfützer R, Real FX, Rebours V, Ridinger M, Rietschel M, Rösmann E, Saftoiu A, Schneider A, Schulz HU, Soranzo N, Soyka M, Simon P, Skipworth J, Stickel F, Strauch K, Stumvoll M, Testoni PA, Tönjes A, Werner L, Werner J, Wodarz N, Ziegler M, Masamune A, Mössner J, Férec C, Michl P, P H Drenth J, Witt H, Scholz M, Sahin-Tóth M. Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis. Gut. 2018 10; 67(10):1855-1863. PMID: 28754779.

    Read at: PubMed
  • Published on 7/1/2017

    Kereszturi É, Sahin-Tóth M. Pancreatic Cancer Cell Lines Heterozygous for the SPINK1 p.N34S Haplotype Exhibit Diminished Expression of the Variant Allele. Pancreas. 2017 07; 46(6):e54-e55. PMID: 28609377.

    Read at: PubMed

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