Miklos Sahin-Toth, MD, PhD

Professor, Molecular & Cell Biology

Miklos Sahin-Toth
617.414.1070
75 E. Newton St Evans Building

Biography

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.

Other Positions

  • Director, Center for Exocrine Disorders, Boston University Henry M. Goldman School of Dental Medicine
  • Research Associate Professor, Biochemistry, Boston University School of Medicine
  • Graduate Faculty (Primary Mentor of Grad Students), Boston University School of Medicine, Division of Graduate Medical Sciences

Education

  • Semmelweis University, MD
  • Semmelweis University, PhD

Publications

  • Published on 10/31/2017

    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.

    Read at: PubMed
  • Published on 7/1/2017

    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.

    Read at: PubMed
  • Published on 11/1/2014

    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.

    Read at: PubMed
  • Published on 10/17/2011

    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.

    Read at: PubMed
  • Published on 8/1/2011

    Zhou J, Sahin-Tóth M. Chymotrypsin C mutations in chronic pancreatitis. J Gastroenterol Hepatol. 2011 Aug; 26(8):1238-46. PMID: 21631589.

    Read at: PubMed
  • Published on 4/22/2011

    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.

    Read at: PubMed
  • Published on 1/1/2011

    Király O, Guan L, Sahin-Tóth M. Expression of recombinant proteins with uniform N-termini. Methods Mol Biol. 2011; 705:175-94. PMID: 21125386.

    Read at: PubMed
  • Published on 11/22/2010

    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. PMID: 21098023.

    Read at: PubMed
  • Published on 5/13/2010

    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.

    Read at: PubMed
  • Published on 5/1/2010

    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.

    Read at: PubMed

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