Sohail Husain

Sohail Husain, MD, Professor, Department of Pediatrics, Divisions of Gastroenterology, Hepatology, and Nutrition, Stanford University School of Medicine

Research Description: Dr. Husain’s early work demonstrated that abnormal acinar cell calcium signals play a crucial role in initiating and transducing acute pancreatitis. Their studies on pathologic calcium signals progressed to determining potent calcium targets leading to pancreatic injury and pancreatitis. They discovered that the calcium-dependent serine, threonine phosphatase calcineurin (Cn) is a novel target of this pathological calcium signal. They used genetic and pharmacologic strategies to examine the role of Cn in clinically relevant experimental models of pancreatitis in vivo and specifically within the pancreatic acinar cell to lay the framework for novel clinical trials that target pancreatitis using Cn inhibitors.  

In the hot pursuit of pancreatitis therapies, the group hypothesized that a novel, alternate strategy to treating pancreatitis would be to examine the factors that turn on pancreatic regeneration and recovery in response to injury. They have thus far determined that HDACs appear to mediate the redifferentiation of intermediate regenerative structures, which are formed during the recovery process, back to mature pancreatic acinar cells. They are currently examining the nuclear HDAC complexes that appear to mediate this role in completing the recovery process. They believe these insights about new gene signatures will unravel novel discoveries that will help devise treatments to counteract organ injury or boost recovery from injury. Drug-induced pancreatitis (DIP) is a leading etiology for pancreatitis in children. However, the mechanisms underlying DIP in the overwhelming majority of drug exposures is completely unknown. A leading culprit in DIP is the crucial cancer drug asparaginase. Using both clinical samples and experimental models, the Husain group has currently focused their efforts on deciphering the mechanisms by which asparaginase predisposes patients to pancreatitis. This work will help devise novel therapies to prevent or mitigate asparaginase-associated pancreatitis and, on a broader level, will help elucidate how drugs can cause pancreatitis. 

Selected relevant publications (SDRC members in BOLD):

  1. Wen L, Javed TA, Dobbs AK, Brown R, Niu M, Li L, Khalid A, Barakat MT, Xiao X, Yimlamai D, Konnikova L, Yu M, Byersdorfer CA, Husain SZ. The Protective Effects of Calcineurin on Pancreatitis in Mice Depend on the Cellular Source. Gastroenterology. 2020 Sep;159(3):1036-1050.e8. doi: 10.1053/j.gastro.2020.05.051. PMID: 32445858; PMCID: PMC7502475. 

  2. Mukherjee A, Ahmed N, Rose FT, Ahmad AN, Javed TA, Wen L, Bottino R, Xiao X, Kilberg MS, Husain SZ. Asparagine Synthetase Is Highly Expressed at Baseline in the Pancreas Through Heightened PERK Signaling. Cell Mol Gastroenterol Hepatol. 2020;9(1):1-13. doi: 10.1016/j.jcmgh.2019.08.003. Epub 2019 Aug 14. PMID: 31421261; PMCID: PMC6881672. 

  3. Mukherjee A, Ahmed N, Rose F, Ahmad AN, Javed TA, Wen L, Bottino, R, Xiao X, Kilberg MS, Husain SZ. Asparagine Synthetase Is Highly Expressed at Baseline in the PancreasThrough Heightened PERK Signaling. Cell Mol Gastroenterol Hepatol. 2019 Aug 14. doi: 10.1016/j.jcmgh.2019.08.003  

  4. Forsmark CE, Andersen DK, Farrar JT, Golden M, Habtezion A, Husain SZ, Li L, Mayerle J, Pandol SJ, Uc A, Zhu Z, Yadav D. Accelerating the Drug Delivery Pipeline for Acute and Chronic Pancreatitis: Summary of the Working Group on Drug Development and Trials in Chronic Pancreatitis at the National Institute of Diabetes and Digestive and Kidney Diseases Workshop. Pancreas. 2018 Nov/Dec;47(10):1200-1207. PMID: 30325858.