The Sahin-Toth Laboratory continues to be vital to the Hirshberg Foundation’s research program, driving groundbreaking discoveries at UCLA. Led by our Scientific Advisory Board Chair, Dr. Miklos Sahin-Toth, the lab is dedicated to unraveling the genetic factors behind hereditary chronic pancreatitis, one of the most significant risk factors for pancreatic cancer. Working closely with Dr. Guido Eibl and the Hirshberg Translational Laboratory, their combined efforts explore the connections between genetics, obesity, diet, and inflammation in pancreatic disease progression.
Dr. Sahin-Toth’s team remains at the forefront of scientific research. The lab contributes to high-impact journals, presents at leading conferences worldwide, and secures ongoing funding from the NIH, which is critical to improving the lives of patients facing pancreatic cancer. We look forward to sharing the latest advancements from his lab and their impact on pancreatic disease research.
Publications from the Sahin-Toth Laboratory in 2024
1. Functional predictors of pathogenicity of missense CPA1 variants in chronic pancreatitis. Gut 2024, 73:1589-1590. PMC11031613.
Sándor M, Sahin-Tóth M.
This seminal study reported the functional characterization of 50 carboxypeptidase A1 (CPA1) variants from patients with chronic pancreatitis and healthy subjects. Unexpectedly, we found that despite measurable functional defects, very few CPA1 variants caused chronic pancreatitis, and most variants reported in the literature were benign. Gut is a preeminent journal in the gastroenterological sciences.
2. Secretagogue-induced pancreatitis in mice devoid of chymotrypsin. American Journal of Physiology-Gastrointestinal and Liver Physiology 2024, 327:G333-G344. PMC11427105. *contributed equally
Demcsák A*, Shariatzadeh S*, Sahin-Tóth M.
An important follow-up study which cemented our contention that the digestive enzyme chymotrypsin protects the pancreas against pancreatitis by reducing harmful intrapancreatic trypsin activity. The American Journal of Physiology – Gastrointestinal and Liver Physiology is an official journal of the American Physiological Society.
3. Novel chymotrypsin C (CTRC) variants from real-world genetic testing of pediatric chronic pancreatitis cases. Pancreatology 2024, 24:690-697. PMC11529566
Stefanovics R, Sándor M, Demcsák A, Berke G, Németh BC, Zhang W, Abu-El-Haija M, Sahin-Tóth M.
This collaborative study analyzed the functional impact of novel chymotrypsin C (CTRC) gene variants identified during real-world genetic testing in a pediatric pancreatitis center. We demonstrated that functional analysis is necessary to distinguish pathogenic risk variants from innocuous genetic variations. Pancreatology is the official journal of the International Association of Pancreatology and the European Pancreatic Club.
4. Heterozygous Spink1 deficiency promotes trypsin-dependent chronic pancreatitis in mice. Cellular and Molecular Gastroenterology and Hepatology 2024, 18:101361. PMC11292374
Demcsák A, Sahin-Tóth M.
This important animal study provided direct evidence that heterozygous loss-of-function mutations in the SPINK1 gene can promote pancreatitis elicited by high intrapancreatic trypsin levels. SPINK1 is a trypsin inhibitor that protects the pancreas by inactivating unwanted trypsin. Cellular and Molecular Gastroenterology and Hepatology is the official research journal of the AGA Institute and it covers a broad spectrum of themes in gastroenterology and pancreatology.
5. Intron-mediated enhancement of SPINK1 expression for pancreatitis therapy. Gut 2024, 74:e9. PMC11631692
Berke G, Sahin-Tóth M.
This is the surprise finding of the year! While studying the expression of the trypsin inhibitor SPINK1 in cell culture, we found that introducing a short intron into the coding DNA could boost mRNA and protein expression by at least 10-fold. This method can inform the design of novel viral vectors for gene therapy against pancreatitis. Gut is a preeminent journal in the gastroenterological sciences.
6. Carboxyl ester lipase hybrid 1 (CEL-HYB1) haplotypes confer varying risk for chronic pancreatitis. Scientific Reports 2024, 14:30965.
Berke G, Sándor M, Xiao XK, Lowe ME, Ewers M, Erőss B, Masson E, Németh BC, Vincze Á, Czakó L, Rygiel AM, Rosendahl J, Chen JM, Witt H, Hegyi P, Sahin-Tóth M*, Hegyi E*. *contributed equally
This collaborative study analyzed the occurrence of a genetic variant of the carboxyl ester lipase gene (called CEL-HYB1) in European populations. We found that CEL-HYB1 existed in two forms; these variants were geographically restricted and had different effects on pancreatitis risk. The Scientific Reports is an open-access journal publishing original research from all areas of life sciences. It is part of the prestigious Nature Research journal family.
7. AlphaMissense versus laboratory-based pathogenicity prediction of 13 novel missense CPA1 variants from pancreatitis cases. Gut 2024 Sep 10. E-publication ahead of print
Sándor M, Scheers I, Masamune A, Witt H, LaRusch J, Chen JM, Németh BC, Geisz A, Uc A, Sahin-Tóth M.
Building on our previous study published earlier in the year (see above, first citation), we investigated whether newly found CPA1 variants in pancreatitis cases were pathogenic. Surprisingly, most variants turned out to be benign. The AI-based program AlphaMissense did not perform well in predicting pathogenicity, indicating that laboratory-based functional analysis is necessary for the correct classification of CPA1 variants detected during genetic testing. Gut is a preeminent journal in the gastroenterological sciences.
8. The high-affinity chymotrypsin Inhibitor Eglin C poorly inhibits human chymotrypsin-like protease: Gln192 and Lys218 are key determinants. Proteins 2024 Sep 20. E-publication ahead of print
Németh BZ, Kiss B, Sahin-Tóth M, Magyar C, Pál G.
This collaborative study investigated the biochemistry of a digestive enzyme, the human chymotrypsin-like protease. It elucidated the reasons for its unique resistance to the leech-derived chymotrypsin inhibitor eglin C. We contributed purified enzymes to the study. The journal “PROTEINS: Structure, Function, and Bioinformatics” publishes original reports in all areas of protein research.
9. Misfolding PRSS1 variant p.Ala61Val in a case of suspected intrauterine pancreatitis. Pancreatology 2024 Dec 24. E-publication ahead of print
Sándor M, Vitale DS, Nagy ZA, Ibrahim SY, Abu-El-Haija M, Lazou M, Vajda S, Sahin-Tóth M.
This collaborative study described and characterized a novel genetic variant in human cationic trypsinogen (PRSS1), which was identified in an infant who suffered pancreatitis while in the womb. Pancreatology is the official journal of the International Association of Pancreatology and the European Pancreatic Club.
