Miklos Sahin-Toth, MD, PhD
Professor
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.

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


Research Associate Professor
Boston University School of Medicine
Biochemistry


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




Chymotrypsin C in Pancreatitis
04/01/2014 - 03/31/2018 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases
5R01DK082412-09

Pancreatice elastases
01/01/2016 - 12/31/2017 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases
4R01DK095753-04

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

Molecular pathomechanism of Hereditary Pancreatitis
09/30/2015 - 06/30/2017 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases
5R01DK058088-15

Pancreatic Elastases
01/01/2013 - 12/31/2015 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases
5R01DK095753-03

Molecular Pathomechanism of Hereditary Pancreatitis
07/01/2010 - 09/29/2015 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases
5R01DK058088-13

Chymotrypsin C in Pancreatitis
04/01/2009 - 03/31/2014 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases
5R01DK082412-05

Andrea Schnur Scholarship
01/01/2011 - 12/31/2012 (PI)
Rosztoczy Foundation

ANDREA SCHNUR SCHOLARSHIP
01/01/2011 - 06/30/2012 (PI)
Rosztoczy Foundation

Rosztoczy Foundation Award to Mentor Andrea Geisz
06/01/2009 - 05/31/2010 (PI)
Rosztoczy Foundation

Showing 10 of 18 results. Show All Results



Yr Title Project-Sub Proj Pubs
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
2013 Pancreatic elastases 1R01DK095753-01A1 12
Showing 10 of 34 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. 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 Jul; 46(6):e54-e55. PMID: 28609377.
  2. 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;.
  3. 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;.
  4. 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;.
  5. 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;.
  6. 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;.
  7. 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;.
  8. 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;.
  9. Szmola R, Sahin-Tóth M. Pancreatitis-associated chymotrypsinogen C (CTRC) mutant elicits endoplasmic reticulum stress in pancreatic acinar cells. Gut. 2010 Mar; 59(3):365-72. PMID: 19951900; PMCID: PMC2848392; DOI: 10.1136/gut.2009.198903;.
  10. Kereszturi E, Sahin-Tóth M. Intracellular autoactivation of human cationic trypsinogen mutants causes reduced trypsinogen secretion and acinar cell death. J Biol Chem. 2009 Nov 27; 284(48):33392-9. PMID: 19801634; PMCID: PMC2785183; DOI: 10.1074/jbc.M109.056812;.
Showing 10 of 33 results. Show More

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

Bar chart showing 33 publications over 11 distinct years, with a maximum of 5 publications in 2006 and 2009

YearPublications
20012
20021
20032
20054
20065
20073
20083
20095
20103
20114
20171
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Boston MA 02118
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