Mulugeta Laboratory

Stress-Neurogastroenterology

Key investigators

• Million Mulugeta, DVM, PhD
• Vincent Wu, PhD
• Muriel Larauche, PhD

Funding

• NIH
• Million Mulugeta, DVM, PhD, Awarded Grant to Map the Peripheral Structural and Functional Neurocircuitries of Visceral Pain of the Colorectum and Bladder (2019)
  
  Dr. Mulugeta was awarded a three-year, HEAL/SPARC grant, through the Office of The Director NIH, NDS Institute, in the amount of $2.2 million to investigate visceral pain afferents involved in the cross-organ sensitization of the colon and bladder through tracing, function assessment and spinal neuromodulation. The project aims to fill gaps in knowledge in the neurocircuitries of pelvic pain cross-sensitization and provide bases for new therapies and modalities including neuromodulation. The project will involve investigators from the UCLA Vatche & Tamar Manoukian Division of Digestive Diseases (Muriel Larauche, PhD; Pu-Qing Yuan, PhD; Lixin Wang, MD, PhD; and Yvette Taché, PhD), as well as investigators from the UCLA Departments of Integrative Biology and Physiology and Neurobiology, USC and SAHMRI at Flinders University, Australia.

Current research projects

• Mechanisms of CRF2 receptor mediated intestinal secretomotor and pain responses to stress
• TBI and intestinal inflammation
• Functional neural circuit mapping of the colon

Future research directions

• CRF1-CRF2 receptors cross talk in enteric neurons during stress
• CRF receptors blockade in TBI related gut dysfunction
• Electorceutical neuromodulation for gut dysmotility

Key publications

1. Million M, Wang L, Wang Y, Adelson DW, Yuan PQ, Maillot C, Coutinho SV, Mcroberts JA, Bayati A, Mattsson H, Wu V, Wei JY, Rivier J, Vale W, Mayer EA, Taché Y. CRF2 receptor activation prevents colorectal distension induced visceral pain and spinal ERK1/2 phosphorylation in rats. Gut. 55(2):172-81 (2006) PMCID: 1856510
2. Million M, Wang L, Adelson DW, Roman F, Diop L, Taché Y. Pregabalin decreases visceral pain and prevents spinal neuronal activation in rats. Gut. (10):1482-4. (2007) PMCID: PMC2000255
3. Gourcerol G, Wang L, Adelson DW, Larauche M, Taché Y, Million M. Cholinergic giant migrating contractions in conscious mouse colon assessed by using a novel noninvasive solid-state manometry method: modulation by stressors. Am J Physiol Gastrointest Liver Physiol. ;296(5):G992-G1002. (2009) PMCID: PMC2696213
4. Gourcerol G, Wu VS, Yuan PQ, Pham H, Miampamba M, Larauche M, Sanders P, Amano T, Rivier J, Taché Y and Million M. Activation of corticotropin-releasing factor receptor 2 mediates the colonic motor coping response to acute stress in rodents. Gastroenterology. 140:1586-1596, (2011)
5. Kashyap PC, Marcobal A, Ursell LK, Larauche M, Duboc H, Earle KA, Sonnenburg ED, Ferreyra JA, Higginbottom SK, Million M, Tache Y, Pasricha PJ, Knight R, Farrugia G, Sonnenburg JL. Complex interactions among diet, gastrointestinal transit, and gut microbiota in humanized mice. Gastroenterology. 2013; 144(5):967-77. PMCID:3890323
6. Akiba Y, Kaunitz JD, Million M. Peripheral corticotropin-releasing factor receptor type 2 activation increases colonic blood flow through nitric oxide pathway in rats. Digestive Diseases and Sciences. 60(4):858-67. NIHMSID: (2015), PMCID: PMC4501405
7. Million M, Larauche M. Stress, sex, and the enteric nervous system. Neurogastroenterology and Motility. 28(9):1283-9. (2016), PMCID: PMC5003424
8. Moussaoui N, Jacobs JP, Larauche M, Biraud M, Million M, Mayer E, Taché Y. Chronic Early-life Stress in Rat Pups Alters Basal Corticosterone, Intestinal Permeability, and Fecal Microbiota at Weaning: Influence of Sex. Journal of Neurogastroenterology and Motility. 23(1):135-143. (2017), PMCID:PMC5216644
9. Wang L, Jacobs JP, Lagishetty V, Yuan PQ, Wu SV, Million M, Reeve JR Jr, Pisegna JR, Taché Y. High-protein diet improves sensitivity to cholecystokinin and shifts the cecal microbiome without altering brain inflammation in diet-induced obesity in rats. American Journal of Physiology. Regulatory, integrative and comparative physiology. 2017; 313(4):R473-R486. PMCID: PMC5668619
10. Tache Y, Larauche M, Yuan PQ, Million M. Brain and Gut CRF Signaling: Biological Actions and Role in the Gastrointestinal Tract. Current Molecular Pharmacology. 11(1):51-71. (2018), PMID:28240194

Bio

Dr. Mulugeta currently leads two research projects on the gut-brain-gut connection through the study of functional and structural circuitry of the autonomic nervous system to pelvic organs (colon and bladder) in health and disease states. These works involve multi-center experts and international teams and are supported by two NIH grants. Dr. Mulugeta is also actively involved in developing novel devices to assess gut secretomotor functions in health and diseases, through SBIR industry-university partnership. In addition, he studies the specific role of CRF2 receptors (CRF2R) in stress-related alteration of colonic function and visceral pain. The project tests the hypothesis that CRFR2 activation modulates stress-related neuroenteric physiology, gut motor function alterations and stress-related visceral pain of colonic origin while CRFR1
 
Dr. Mulugeta has published several papers on the brain-gut interaction and stress related gastrointestinal motility, pain and inflammatory responses. He is peer-reviewer for numerous medical journals, and serves as editorial board member for the American Journal of Physiology and the Journal of Digestive Diseases & Science. Dr. Mulugeta serves as a reviewer at special emphasis panels of NIH. He is recipient of several awards including the 2011 International Foundation for Functional Gastrointestinal Disorders award in basic sciences.