Digestive Diseases Research

Mulugeta Laboratory

Million Mulugeta, DVM, PhD

Stress-Neurogastroenterology

Key investigators

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

Other lab members

  • Andrea Tamayo, Lab manager
  • Trisha Parthasarathi, UCLA undergraduate student

Funding

  • NIH
    • U01NS113871-01 (Million Mulugeta, PI); Title: Structural and Functional Mapping of Visceral Pain Afferent Neurocircuitries of the Colorectum and Bladder in Preclinical Models
    • OT2OD024899 (Yvette Taché and Million Mulugeta, Co-PD/PI); Title: Comprehensive Structural and Functional Mapping of Mammalian Colonic Nervous System
    • OT2OD025297 01S3 (Gaunt Robert at PITT, PI; Million Mulugeta, Sub-Contract PI); Title: Soft Silicone Electrode Nets: Implantable Technology For Visceral Organ Neural Interfacing And Functional Evaluation
  • NSF
    • 1938625: (Yi-Kai Lu, PI; Million Mulugeta, UCLA PI); SBIR Phase IIB; Title: An Ingestible Intraluminal Bioelectronic Capsule (IBC) for Closed-Loop Diagnosis and Treatment of Gastrointestinal Disorders
  • 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 - Full list on PubMed(Link is external) (Link opens in new window)

  1. Wang Y, Wang PM, Larauche M, Mulugeta M, Liu W. Bio-impedance method to monitor colon motility response to direct distal colon stimulation in anesthetized pigs(Link is external). Sci Rep. 2022 Aug 12:12(1):13761. doi: 10.1038/s41598-022-17549-6
  2. Mazzoni M, Caremoli F, Cabanillas L, de los Santos J, Million M, Larauche M, Clavenzani P, De Giorgio R, Sternini C. Quantitative analysis of enteric neurons containing choline acetyltransferase and nitric exide synthase immunoreactivities in the submucosal and myenteric plexus of the porcine colon(Link is external) (Link opens in new window).  Cell Tissue Res. 2021 Feb;383(2):645-654. doi: 10.1007/s00441-020-03286-7. Epub 2020 Sep 23
  3. Larauche M, Wang Y, Wang PM, Dubrovsky G, Lo YK, Hsiang EL, Dunn JCY, Taché Y, Million M. The effect of colonic tissue electrical stimulation and celiac branch of the abdominal vagus nerve neuromodulation on colonic motility in anesthetized pigs(Link is external) (Link opens in new window). Neurogastroenterol Motil. 2020 Nov;32(11):e13925.doi: 10.1111/nmo.13925. Epub 2020 Jun 23
  4. 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(Link is external). Gut. 55(2):172-81 (2006) PMCID: 1856510
  5. Million M, Wang L, Adelson DW, Roman F, Diop L, Taché Y. Pregabalin decreases visceral pain and prevents spinal neuronal activation in rats(Link is external). Gut. (10):1482-4. (2007) PMCID: PMC2000255
  6. 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(Link is external). Am J Physiol Gastrointest Liver Physiol. ;296(5):G992-G1002. (2009) PMCID: PMC2696213
  7. Gourcerol G, Wu VS, Yuan PQ, Pham H, Miampamba M, Larauche M, Sanders P, Amano T, Rivier J, Taché Y, Million M. Activation of corticotropin-releasing factor receptor 2 mediates the colonic motor coping response to acute stress in rodents(Link is external). Gastroenterology. 140:1586-1596, (2011)
  8. 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(Link is external). Gastroenterology. 2013; 144(5):967-77. PMCID:3890323
  9. Akiba Y, Kaunitz JD, Million M. Peripheral corticotropin-releasing factor receptor type 2 activation increases colonic blood flow through nitric oxide pathway in rats(Link is external). Digestive Diseases and Sciences. 60(4):858-67. NIHMSID: (2015), PMCID: PMC4501405
  10. MMillion M, Larauche M. Stress, sex, and the enteric nervous system(Link is external). Neurogastroenterology and Motility. 28(9):1283-9. (2016), PMCID: PMC5003424
  11. 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(Link is external). Journal of Neurogastroenterology and Motility. 23(1):135-143. (2017), PMCID:PMC5216644
  12. 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(Link is external). American Journal of Physiology. Regulatory, integrative and comparative physiology. 2017; 313(4):R473-R486. PMCID: PMC5668619
  13. Tache Y, Larauche M, Yuan PQ, Million M. Brain and gut CRF signaling: Biological actions and role in the gastrointestinal tract(Link is external). Current Molecular Pharmacology. 11(1):51-71. (2018), PMID:28240194

About Dr. Mulugeta

Dr. Mulugeta currently leads three NIH supported 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 a University PI on a National Science Foundation supported research to develop novel devices (smart pill) 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 a reviewer for numerous medical journals and serves as editorial board member for the American Journal of Physiology. Dr. Mulugeta serves as a member to several special emphasis panel of NIH to review grant applications. He is recipient of several awards including the 2011 International Foundation for Functional Gastrointestinal Disorders award in basic sciences.