Miklos Sahin-Toth, MD, PhD
Boston University Henry M. Goldman School of Dental Medicine
Dept of 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.

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

Research Associate Professor
Boston University School of Medicine

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

Trypsin-dependent mechanisms in pancreatitis
07/01/2018 - 03/31/2023 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases

Molecular pathomechanism of Hereditary Pancreatitis
09/30/2015 - 06/30/2020 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases

Digestive enzyme misfolding promotes alcoholic pancreatitis
02/15/2018 - 01/31/2020 (PI)
NIH/National Institute on Alcohol Abuse and Alcoholism

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

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

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

Chymotrypsin C in Pancreatitis
04/01/2009 - 03/31/2014 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases

Showing 10 of 21 results. Show All Results

Yr Title Project-Sub Proj Pubs
2018 Digestive enzyme misfolding promotes alcoholic pancreatitis 1R21AA026456-01
2017 Chymotrypsin C in pancreatitis 5R01DK082412-09 20
2016 Pancreatic elastases 4R01DK095753-04 12
2016 Chymotrypsin C in pancreatitis 5R01DK082412-08 20
2016 Molecular pathomechanism of hereditary pancreatitis 5R01DK058088-15 58
2015 Pancreatic elastases 5R01DK095753-03 12
2015 Chymotrypsin C in pancreatitis 5R01DK082412-07 20
2015 Molecular pathomechanism of hereditary pancreatitis 2R01DK058088-14 58
2014 Pancreatic elastases 5R01DK095753-02 12
2014 Chymotrypsin C in pancreatitis 2R01DK082412-06 20
Showing 10 of 35 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.

  1. 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.
  2. 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.
  3. Freeman M, Pandol SJ, Liddle RA, Saluja AK, Fernandez-Del Castillo C, Maitra A, Sahin-Toth M, Go VL. Minutes of the business meeting of the american pancreatic association, friday, november 1, 2013, miami, Florida. Pancreas. 2014 Nov; 43(8):1141-2. PMID: 25333397; DOI: 10.1097/MPA.0000000000000227;.
  4. Bence M, Sahin-Tóth M. Asparagine-linked glycosylation of human chymotrypsin C is required for folding and secretion but not for enzyme activity. FEBS J. 2011 Nov; 278(22):4338-50. PMID: 21920023; PMCID: PMC3209518; DOI: 10.1111/j.1742-4658.2011.08351.x;.
  5. Zhou J, Sahin-Tóth M. Chymotrypsin C mutations in chronic pancreatitis. J Gastroenterol Hepatol. 2011 Aug; 26(8):1238-46.View Related Profiles. PMID: 21631589; PMCID: PMC3142265; DOI: 10.1111/j.1440-1746.2011.06791.x;.
  6. Szabó A, Héja D, Szakács D, Zboray K, Kékesi KA, Radisky ES, Sahin-Tóth M, Pál G. High affinity small protein inhibitors of human chymotrypsin C (CTRC) selected by phage display reveal unusual preference for P4' acidic residues. J Biol Chem. 2011 Jun 24; 286(25):22535-45. PMID: 21515688; PMCID: PMC3121398; DOI: 10.1074/jbc.M111.235754;.
  7. Király O, Guan L, Sahin-Tóth M. Expression of recombinant proteins with uniform N-termini. Methods Mol Biol. 2011; 705:175-94. PMID: 21125386; PMCID: PMC3107599; DOI: 10.1007/978-1-61737-967-3_10;.
  8. Szmola R, Bence M, Carpentieri A, Szabó A, Costello CE, Samuelson J, Sahin-Tóth M. Chymotrypsin C is a co-activator of human pancreatic procarboxypeptidases A1 and A2. J Biol Chem. 2011 Jan 21; 286(3):1819-27.View Related Profiles. PMID: 21098023; PMCID: PMC3023477; DOI: 10.1074/jbc.M110.187369;.
  9. Rosendahl J, Teich N, Kovacs P, Szmola R, Blüher M, Gress TM, Hoffmeister A, Keim V, Löhr M, Mössner J, Nickel R, Ockenga J, Pfützer R, Schulz HU, Stumvoll M, Wittenburg H, Sahin-Tóth M, Witt H. Complete analysis of the human mesotrypsinogen gene (PRSS3) in patients with chronic pancreatitis. Pancreatology. 2010; 10(2-3):243-9. PMID: 20484962; PMCID: PMC2899151; DOI: 10.1159/000243769;.
  10. Szmola R, Sahin-Tóth M. Uncertainties in the classification of human cationic trypsinogen (PRSS1) variants as hereditary pancreatitis-associated mutations. J Med Genet. 2010 May; 47(5):348-50. PMID: 20452997; PMCID: PMC2930840; DOI: 10.1136/jmg.2009.072751;.
Showing 10 of 35 results. Show More

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

Bar chart showing 35 publications over 12 distinct years, with a maximum of 5 publications in 2006 and 2009

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75 E. Newton St Evans Building
Boston MA 02118
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