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




Trypsin-dependent mechanisms in pancreatitis
07/01/2018 - 03/31/2023 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases
1R01DK117809-01

Molecular pathomechanism of Hereditary Pancreatitis
09/30/2015 - 06/30/2020 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases
5R01DK058088-17

Digestive enzyme misfolding promotes alcoholic pancreatitis
02/15/2018 - 01/31/2020 (PI)
NIH/National Institute on Alcohol Abuse and Alcoholism
1R21AA026456-01

Chymotrypsin C in Pancreatitis
04/01/2014 - 03/31/2019 (PI)
NIH/National Diabetes & Digestive & Kidney Diseases
5R01DK082412-09

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
4R01DK095753-04

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
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

Showing 10 of 21 results. Show All Results



Yr Title Project-Sub Proj Pubs
2018 Trypsin-dependent mechanisms in pancreatitis 1R01DK117809-01
2018 Digestive enzyme misfolding promotes alcoholic pancreatitis 1R21AA026456-01
2018 Molecular pathomechanism of hereditary pancreatitis 5R01DK058088-17 58
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
Showing 10 of 37 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. Jancsó Z, Hegyi E, Sahin-Tóth M. Chymotrypsin Reduces the Severity of Secretagogue-induced Pancreatitis in Mice. Gastroenterology. 2018 Aug 01. PMID: 30076839.
     
  2. Hegyi E, Sahin-Tóth M. Human CPA1 mutation causes digestive enzyme misfolding and chronic pancreatitis in mice. Gut. 2018 Jul 25. PMID: 30045879.
     
  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.
     
  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; 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.
     
  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.
     
  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.
     
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

YearPublications
20013
20024
20034
20041
20056
20068
20074
20083
20097
20105
20117
20123
20136
20145
201512
20169
201713
20183
In addition to these self-described keywords below, a list of MeSH based concepts is available here.

proteases
Pancreatitis
Contact for Mentoring:


75 E. Newton St Evans Building
Boston MA 02118
Google Map


Sahin-Toth's Networks
Click the "See All" links for more information and interactive visualizations
Concepts
_
Co-Authors
_
Similar People
_
Same Department