Miklos Sahin-Toth, MD, PhD
Adjunct Professor
Boston University Henry M. Goldman School of Dental Medicine
Molecular & Cell Biology

MD, Semmelweis University
PhD, Semmelweis University

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.

Research Associate Professor
Boston University Chobanian & Avedisian School of Medicine
Biochemistry & Cell Biology

Boston University Henry M. Goldman School of Dental Medicine
Center for Exocrine Disorders

Graduate Faculty (Primary Mentor of Grad Students)
Boston University Chobanian & Avedisian School of Medicine, Graduate Medical Sciences

Molecular Pathomechanism of Hereditary Pancreatitis
09/30/2015 - 03/31/2019 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases

Chymotrypsin C in Pancreatitis
04/01/2014 - 03/31/2019 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases

Trypsin-dependent mechanisms in pancreatitis
07/01/2018 - 02/28/2019 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases

Digestive enzyme misfolding promotes alcoholic pancreatitis
02/15/2018 - 02/28/2019 (PI)
NIH/National Institute on Alcohol Abuse and Alcoholism

study of one of the human digestive enzynes named elastase (Rosztoczy Foundation Schloarship Award)
01/01/2018 - 12/31/2018 (PI)
Rosztoczy Foundation

Pancreatice elastases
01/01/2016 - 12/31/2017 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases

Mouse Model of Human Hereditary Pancreatitis
09/01/2014 - 08/31/2017 (PI)
Department of Defense/Army Medical Research Acquisition Activity

Genomic structural variants at the CTRB1/CTRB2 locus in chronic pancreatitis
06/01/2016 - 05/31/2017 (Key Person / Mentor)
The National Pancreas Foundation

Pancreatic Elastases
01/01/2013 - 12/31/2015 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases

Molecular Pathomechanism of Hereditary Pancreatitis
07/01/2010 - 09/29/2015 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases

Showing 10 of 22 results. Show All Results


Yr Title Project-Sub Proj Pubs
2024 Chymotrypsin in pancreatitis 5R01DK082412-13
2023 Chymotrypsin in pancreatitis 5R01DK082412-12
2022 Trypsin-dependent mechanisms in pancreatitis 5R01DK117809-05
2022 Chymotrypsin in pancreatitis 5R01DK082412-11
2021 Trypsin-dependent mechanisms in pancreatitis 5R01DK117809-04 2
2021 Chymotrypsin in pancreatitis 2R01DK082412-10A1 35
2020 Trypsin-dependent mechanisms in pancreatitis 5R01DK117809-03 2
2019 Trypsin-dependent mechanisms in pancreatitis 7R01DK117809-02 2
2019 Digestive enzyme misfolding promotes alcoholic pancreatitis 5R21AA026456-02
2019 Digestive enzyme misfolding promotes alcoholic pancreatitis 7R21AA026456-03
Showing 10 of 49 results. Show All Results

Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.

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  1. 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; PMCID: PMC6200337; DOI: 10.1053/j.gastro.2018.06.041;
  2. 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; PMCID: PMC6326849; DOI: 10.1136/gutjnl-2018-315994;
  3. 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
  4. 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; PMCID: PMC5933932; DOI: 10.1038/ajg.2017.393;
  5. Sahin-Tóth M. Partial and complete SPINK1 deficiency cause distinct pancreatic phenotypes. Hum Mutat. 2017 12; 38(12):1619. PMID: 29091332
  6. 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
  7. 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; PMCID: PMC5722094; DOI: 10.1136/bmjopen-2017-015874;
  8. Sahin-Tóth M. Genetic risk in chronic pancreatitis: the misfolding-dependent pathway. Curr Opin Gastroenterol. 2017 Sep; 33(5):390-395. PMID: 28650851; PMCID: PMC5549634; DOI: 10.1097/MOG.0000000000000380;
  9. 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.View Related Profiles. PMID: 28754779; PMCID: PMC6145291; DOI: 10.1136/gutjnl-2017-314454;
  10. 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; PMCID: PMC5470582; DOI: 10.1097/MPA.0000000000000817;
Showing 10 of 103 results. Show More

This graph shows the total number of publications by year, by first, middle/unknown, or last author.

Bar chart showing 103 publications over 18 distinct years, with a maximum of 13 publications in 2017


In addition to these self-described keywords below, a list of MeSH based concepts is available here.

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75 E. Newton St Evans Building
Boston MA 02118
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