Keywords
Last Name

Miklos Sahin-Toth, MD, PhD

TitleProfessor
InstitutionBoston University Goldman School of Dental Medicine
DepartmentMolecular & Cell Biology
Address75 E. Newton St
Boston MA 02118
Phone(617) 414-1070
ORCID ORCID Icon0000-0003-4513-9922
Other Positions
TitleGraduate Faculty (Primary Mentor of Grad Students)
InstitutionBoston University School of Medicine
DepartmentGraduate Medical Sciences, Division of

TitleResearch Associate Professor
InstitutionBoston University School of Medicine
DepartmentBiochemistry

 Research Expertise & Professional Interests
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.

 NIH RePORTER Grants
 Publications
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. 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.
    View in: PubMed
  2. Zhou J, Sahin-Tóth M. Chymotrypsin C mutations in chronic pancreatitis. J Gastroenterol Hepatol. 2011 Aug; 26(8):1238-46.
    View in: PubMed
  3. 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.
    View in: PubMed
  4. Király O, Guan L, Sahin-Tóth M. Expression of recombinant proteins with uniform N-termini. Methods Mol Biol. 2011; 705:175-94.
    View in: PubMed
  5. 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 in: PubMed
  6. 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.
    View in: PubMed
  7. 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.
    View in: PubMed
  8. 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.
    View in: PubMed
  9. 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.
    View in: PubMed
  10. Medveczky P, Szmola R, Sahin-Tóth M. Proteolytic activation of human pancreatitis-associated protein is required for peptidoglycan binding and bacterial aggregation. Biochem J. 2009 Jun 1; 420(2):335-43.
    View in: PubMed
  11. Kereszturi E, Szmola R, Kukor Z, Simon P, Weiss FU, Lerch MM, Sahin-Tóth M. Hereditary pancreatitis caused by mutation-induced misfolding of human cationic trypsinogen: a novel disease mechanism. Hum Mutat. 2009 Apr; 30(4):575-82.
    View in: PubMed
  12. Rónai Z, Witt H, Rickards O, Destro-Bisol G, Bradbury AR, Sahin-Tóth M. A common African polymorphism abolishes tyrosine sulfation of human anionic trypsinogen (PRSS2). Biochem J. 2009 Feb 15; 418(1):155-61.
    View in: PubMed
  13. Kereszturi E, Király O, Sahin-Tóth M. Minigene analysis of intronic variants in common SPINK1 haplotypes associated with chronic pancreatitis. Gut. 2009 Apr; 58(4):545-9.
    View in: PubMed
  14. Sahin-Tóth M, Hegyi P, Tóth M. [Genetic risk factors in chronic pancreatitis]. Orv Hetil. 2008 Sep 7; 149(36):1683-8.
    View in: PubMed
  15. Ozsvári B, Hegyi P, Sahin-Tóth M. The guinea pig pancreas secretes a single trypsinogen isoform, which is defective in autoactivation. Pancreas. 2008 Aug; 37(2):182-8.
    View in: PubMed
  16. Szmola R, Sahin-Tóth M. Chymotrypsin C (caldecrin) promotes degradation of human cationic trypsin: identity with Rinderknecht's enzyme Y. Proc Natl Acad Sci U S A. 2007 Jul 3; 104(27):11227-32.
    View in: PubMed
  17. Király O, Wartmann T, Sahin-Tóth M. Missense mutations in pancreatic secretory trypsin inhibitor (SPINK1) cause intracellular retention and degradation. Gut. 2007 Oct; 56(10):1433-8.
    View in: PubMed
  18. Király O, Boulling A, Witt H, Le Maréchal C, Chen JM, Rosendahl J, Battaggia C, Wartmann T, Sahin-Tóth M, Férec C. Signal peptide variants that impair secretion of pancreatic secretory trypsin inhibitor (SPINK1) cause autosomal dominant hereditary pancreatitis. Hum Mutat. 2007 May; 28(5):469-76.
    View in: PubMed
  19. Sahin-Tóth M, Kukor Z, Nemoda Z. Human cationic trypsinogen is sulfated on Tyr154. FEBS J. 2006 Nov; 273(22):5044-50.
    View in: PubMed
  20. Szepessy E, Sahin-Tóth M. Human mesotrypsin exhibits restricted S1' subsite specificity with a strong preference for small polar side chains. FEBS J. 2006 Jul; 273(13):2942-54.
    View in: PubMed
  21. Sahin-Tóth M. Biochemical models of hereditary pancreatitis. Endocrinol Metab Clin North Am. 2006 Jun; 35(2):303-12, ix.
    View in: PubMed
  22. Nemoda Z, Sahin-Tóth M. Chymotrypsin C (caldecrin) stimulates autoactivation of human cationic trypsinogen. J Biol Chem. 2006 Apr 28; 281(17):11879-86.
    View in: PubMed
  23. Király O, Guan L, Szepessy E, Tóth M, Kukor Z, Sahin-Tóth M. Expression of human cationic trypsinogen with an authentic N terminus using intein-mediated splicing in aminopeptidase P deficient Escherichia coli. Protein Expr Purif. 2006 Jul; 48(1):104-11.
    View in: PubMed
  24. Szepessy E, Sahin-Tóth M. Inactivity of recombinant ELA2B provides a new example of evolutionary elastase silencing in humans. Pancreatology. 2006; 6(1-2):117-22.
    View in: PubMed
  25. Sahin-Tóth M. Human mesotrypsin defies natural trypsin inhibitors: from passive resistance to active destruction. Protein Pept Lett. 2005 Jul; 12(5):457-64.
    View in: PubMed
  26. Nemoda Z, Sahin-Tóth M. The tetra-aspartate motif in the activation peptide of human cationic trypsinogen is essential for autoactivation control but not for enteropeptidase recognition. J Biol Chem. 2005 Aug 19; 280(33):29645-52.
    View in: PubMed
  27. Nemoda Z, Teich N, Hugenberg C, Sahin-Tóth M. Genetic and biochemical characterization of the E32del polymorphism in human mesotrypsinogen. Pancreatology. 2005; 5(2-3):273-8.
    View in: PubMed
  28. Szmola R, Kukor Z, Sahin-Tóth M. Human mesotrypsin is a unique digestive protease specialized for the degradation of trypsin inhibitors. J Biol Chem. 2003 Dec 5; 278(49):48580-9.
    View in: PubMed
  29. Kukor Z, Tóth M, Sahin-Tóth M. Human anionic trypsinogen: properties of autocatalytic activation and degradation and implications in pancreatic diseases. Eur J Biochem. 2003 May; 270(9):2047-58.
    View in: PubMed
  30. Guan L, Sahin-Toth M, Kaback HR. Changing the lactose permease of Escherichia coli into a galactose-specific symporter. Proc Natl Acad Sci U S A. 2002 May 14; 99(10):6613-8.
    View in: PubMed
  31. Simon P, Weiss FU, Sahin-Toth M, Parry M, Nayler O, Lenfers B, Schnekenburger J, Mayerle J, Domschke W, Lerch MM. Hereditary pancreatitis caused by a novel PRSS1 mutation (Arg-122 --> Cys) that alters autoactivation and autodegradation of cationic trypsinogen. J Biol Chem. 2002 Feb 15; 277(7):5404-10.
    View in: PubMed
  32. Sahin-Toth M, Kaback HR. Arg-302 facilitates deprotonation of Glu-325 in the transport mechanism of the lactose permease from Escherichiacoli. Proc Natl Acad Sci U S A. 2001 May 22; 98(11):6068-73.
    View in: PubMed
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