Sam Cheng, M.D., M.Sc., Ph.D.
(352) 273-9350 (phone)
(352) 273-9055 (fax)
- M.D., Tongji Medical University, China
- Ph.D. Karolinska Institute, Sweden, Physiology
- WHO fellow, Institute of Child Health/University College London, UK, Genetics
- Postdoctoral, Vanderbilt University, TN, Physiology
- Resident, State University of New York @ Downstate, NY, Pediatrics
- Fellow, Yale University, CT, Pediatric Gastroenterology
Acute infectious diarrhea is a worldwide problem, especially among infants and young children. Still, millions of children die each year, not as a result of infections per se but from the associated dehydration. The currently recommended Oral Rehydration Solution (ORS) can replace, but not reduce, the fluid loss from diarrhea. Also, it does not treat the inflammation component of diarrhea. Although there are a few anti-secretory therapies available or in development, they are very expensive and are not affordable or available. In addition, none of the current diarrhea therapies, including the pro-absorptive ORS or the anti-secretory therapies, have notable effects to treat malnutrition, impaired growth and development – sequelae associated with diarrhea. Thus, new therapeutic approaches for diarrhea are needed along with an enhanced understanding of mediators of intestinal fluid transport.
Dr. Cheng’s research is focused on discovering anti-secretory, anti-motility, and anti-inflammatory mechanisms in the gut that reduce the magnitude and duration of diarrhea, both secretory and inflammatory.
His studies aim to identify an important cellular system that exerts profound effects on intestinal function, motility, and inflammation. Additional to routine molecular cellular and immunopathological approaches, Dr. Cheng will employ state of art optogenetic and microscopic methods in combination with classical physiological and electrophysiological techniques. Currently, the laboratory focuses on the calcium-sensing receptor, a conserved nutrient sensor in the gut. The ultimate goal of this research is to define a simple nutrition-based anti-diarrheal therapy that might have clinical utility in billions of infants and children worldwide.
After obtaining his MD and MSc in clinical investigation, Dr. Cheng was trained in molecular biology and genetics while being a W.H.O fellow at Great Ormond Street Hospital in London. Subsequently, he applied this knowledge and skills to his Ph.D study at Karolinska Institue, and characterized hormonal regulation of this ion pump by second messenger-mediated phosphorylation signaling. As a postdoctoral fellow at Vanderbilt and Yale, he expanded his training in ion transport physiology to include FEN (fluid/electrolyte/nutrition) and CaSR (calcium-sensing receptor) physiology and pathology, in relation to the GI diseases in children. This work resulted in publications in AJP, Gastroenterology and PNAS. It also laid the groundwork for his proposed research herein. The current work builds logically on his prior work and previous training in combination with his current interests as a GI physiologist and pediatric gastroenterologist. He is especially interested in IBD (inflammatory bowel disease), IBS (irritable bowel syndrome) and other diarrheal disorders in children.
Calcium-Sensing Receptor (CaSR) Nutrient-Based Therapies for Diarrhea in Children
- Tang L, Fang X, Winesett SP, Cheng CY, Binder HJ, Rivkees SA & Cheng SX (2017). Bumetanide increases Cl–dependent short-circuit current in late distal colon: evidence for the presence of active electrogenic Cl- absorption. PLOS ONE 12(2):e0171045
- Tang L, Cheng CY, Sun X, Pedicone AJ, Mohamadzadeth M & Cheng SX (2016). The Extracellular Calcium-Sensing Receptor in the Intestine: Evidence for Regulation of Colonic Absorption, Secretion, Motility, and Immunity. Front Physiol 7:245. doi: 10.3389/fphys.2016.00245
- Cheng SX (2016). Calcium-sensing receptor: A new target for therapy of diarrhea. World J Gastroenterol 22(9):2711-24.
- Owen JL, Cheng SX, Sahay B & Mohamadzadeh M (2016). The Role of the Calcium-Sensing Receptor in Gastrointestinal Inflammation. Seminar Cell Dev Biol 49:44-51.
- Tang L, Peng M, Liu L, Chang W, Binder HJ &Cheng SX (2015). Calcium-Sensing Receptor Stimulates Cl– and SCFA-dependent but Inhibits cAMP-dependent HCO3- Secretion in Colon. Am J Physiol. 308(10):G874-83
- Cheng SX, Lightfoot YL, Yang T, Zadeh M, Tang L, Sahay B, Wang GP, Owen JL & Mohamadzadeh M (2014). Epithelial CaSR Deficiency Alters Intestinal Integrity and Promotes Proinflammatory Immune Responses. FEBS Lett. 588: 4158-66.
- Cheng SX, Bai HX, Gonzalez-Peralta R, Mistry PK & Gorelick FS (2013). Calcium ameliorates diarrhea in immunocompromised children. J Pediatr Gastroenterol Nutr. 56: 641-4.
- Ring A*, Cheng SX*, Kahle KT, Leng Q, Rinehart J, Lalioti MD, Volkman HM, Wilson FH, Hebert SC & Lifton RP (2007). WNK4 regulates activity of the epithelial Na channel in vitro and in vivo. PNAS, 104:4020-4. * shared 1st authorship
- Geibel J, Sritharan K, Geibel R, Geibel P, Persing JS, Seeger A, Roepke TK, Deichstetter M, Prinz C, Cheng SX, Martin D & Hebert SC (2006). Calcium-sensing receptor abrogates secretagogue-induced increases in intestinal net fluid secretion by enhancing cyclic nucleotide destruction. PNAS, 103: 9390-7.
- Fisone G, Cheng SX-J, Nairn AC, Czernik AJ, Hemmings HC Jr, Höög J-O, Bertorello AM, Kaiser R, Bergman T, Jörnvall H, Aperia A & Greengard P (1994). Identification of the phosphorylation site for cAMP-dependent protein kinase on Na+,K+-ATPase and and effects of site-directed mutagenesis. J Biol Chem 269: 9368-9373.
- Nowicki S, Chen SL, Aizman O, Cheng X-J, Li D, Nowicki C, Nairn AC, Greengard P & Aperia A(1997). 20-Hydroxyeicosa-tetraenoic acid (20 HETE) activates protein kinase C. Role in regulation of rat renal Na+,K+-ATPase. J Clin Invest 99: 1224-1230.
- Cheng SXJ, Aizman O, Nairn A, Greengard P & Aperia A (1999). [Ca2+]i determines the effects of protein kinases A and C on activity of rat renal Na+,K+-ATPase. J Physiol 518: 37-46.
- Lal MA, Korner A, Matsuo Y, Zelenin S, Cheng SX, Jaremko G, DiBona G F, Eklof A C & Aperia A (2000). Combined antioxidant and COMT inhibitor treatment reverses renal abnormalities in diabetic rats. Diabetes 49(8):138.
- Cheng SX, Okuda M, Hall AE, Geibel JP & Hebert SC (2002). Expression of calcium/nutrient-sensing receptor in rat colonic epithelium: evidence for modulation of fluid secretion. Am J Physiol 283:G240-G250
- Cheng SX, Geibel JP & Hebert SC (2004). Extracellular polyamines regulate fluid secretion in rat colonic crypts via the extracellular calcium-sensing receptor. Gastroenterology 126(1):148-58.
- Cheng SX, Gathungu G, Pashankar D, Jain D & Husain S (2011). Jejunal adaptation in a pre-pubertal boy after total ileal resection and jejunostomy placement: a 4 year follow-up. J Clin Gastroenterol 2011;45:846-9.
- Cheng SX (2012). Calcium-sensing receptor inhibits secretagogue-induced electrolyte secretion by intestine via the enteric nervous system. Am J Physiology 303(1):G60-70