Publications

Associate Professor of Medicine (Gastroenterology and Hepatology); Associate Dean, Academic Affairs, School of Medicine

Publications

  • p38γ and p38δ as biomarkers in the interplay of colon cancer and inflammatory bowel diseases. Cancer communications (London, England) Fajardo, P., Taskova, M., Martín-Serrano, M. A., Hansen, J., Slott, S., Jakobsen, A. K., Wibom, M. L., Salegi, B., Muñoz, A., Barbachano, A., Sharma, A., Gubatan, J. M., Habtezion, A., Sanz-Ezquerro, J. J., Astakhova, K., Cuenda, A. 2022

    View details for DOI 10.1002/cac2.12331

    View details for PubMedID 35796643

  • A tissue-like neurotransmitter sensor for the brain and gut. Nature Li, J., Liu, Y., Yuan, L., Zhang, B., Bishop, E. S., Wang, K., Tang, J., Zheng, Y., Xu, W., Niu, S., Beker, L., Li, T. L., Chen, G., Diyaolu, M., Thomas, A., Mottini, V., Tok, J. B., Dunn, J. C., Cui, B., Pașca, S. P., Cui, Y., Habtezion, A., Chen, X., Bao, Z. 2022; 606 (7912): 94-101

    Abstract

    Neurotransmitters play essential roles in regulating neural circuit dynamics both in the central nervous system as well as at the peripheral, including the gastrointestinal tract1-3. Their real-time monitoring will offer critical information for understanding neural function and diagnosing disease1-3. However, bioelectronic tools to monitor the dynamics of neurotransmitters in vivo, especially in the enteric nervous systems, are underdeveloped. This is mainly owing to the limited availability of biosensing tools that are capable of examining soft, complex and actively moving organs. Here we introduce a tissue-mimicking, stretchable, neurochemical biological interface termed NeuroString, which is prepared by laser patterning of a metal-complexed polyimide into an interconnected graphene/nanoparticle network embedded in an elastomer. NeuroString sensors allow chronic in vivo real-time, multichannel and multiplexed monoamine sensing in the brain of behaving mouse, as well as measuring serotonin dynamics in the gut without undesired stimulations and perturbing peristaltic movements. The described elastic and conformable biosensing interface has broad potential for studying the impact of neurotransmitters on gut microbes, brain-gut communication and may ultimately be extended to biomolecular sensing in other soft organs across the body.

    View details for DOI 10.1038/s41586-022-04615-2

    View details for PubMedID 35650358

  • Metalloendopeptidase ADAM-like Decysin 1 (ADAMDEC1) in Colonic Subepithelial PDGFRalpha+ Cells Is a New Marker for Inflammatory Bowel Disease. International journal of molecular sciences Ha, S. E., Jorgensen, B. G., Wei, L., Jin, B., Kim, M., Poudrier, S. M., Singh, R., Bartlett, A., Zogg, H., Kim, S., Baek, G., Kurahashi, M., Lee, M., Kim, Y., Choi, S., Sasse, K. C., Rubin, S. J., Gottfried-Blackmore, A., Becker, L., Habtezion, A., Sanders, K. M., Ro, S. 2022; 23 (9)

    Abstract

    Metalloendopeptidase ADAM-Like Decysin 1 (ADAMDEC1) is an anti-inflammatory peptidase that is almost exclusively expressed in the gastrointestinal (GI) tract. We have recently found abundant and selective expression of Adamdec1 in colonic mucosal PDGFRalpha+ cells. However, the cellular origin for this gene expression is controversial as it is also known to be expressed in intestinal macrophages. We found that Adamdec1 mRNAs were selectively expressed in colonic mucosal subepithelial PDGFRalpha+ cells. ADAMDEC1 protein was mainly released from PDGFRalpha+ cells and accumulated in the mucosal layer lamina propria space near the epithelial basement membrane. PDGFRalpha+ cells significantly overexpressed Adamdec1 mRNAs and protein in DSS-induced colitis mice. Adamdec1 was predominantly expressed in CD45- PDGFRalpha+ cells in DSS-induced colitis mice, with only minimal expression in CD45+ CD64+ macrophages. Additionally, overexpression of both ADAMDEC1 mRNA and protein was consistently observed in PDGFRalpha+ cells, but not in CD64+ macrophages found in human colonic mucosal tissue affected by Crohn's disease. In summary, PDGFRalpha+ cells selectively express ADAMDEC1, which is localized to the colon mucosa layer. ADAMDEC1 expression significantly increases in DSS-induced colitis affected mice and Crohn's disease affected human tissue, suggesting that this gene can serve as a diagnostic and/or therapeutic target for intestinal inflammation and Crohn's disease.

    View details for DOI 10.3390/ijms23095007

    View details for PubMedID 35563399

  • The effect of gastric acid suppression on probiotic colonization in a double blinded randomized clinical trial. Clinical nutrition ESPEN Singh, G., Haileselassie, Y., Briscoe, L., Bai, L., Patel, A., Sanjines, E., Hendler, S., Singh, P. K., Garud, N. R., Limketkai, B. N., Habtezion, A. 1800; 47: 70-77

    Abstract

    BACKGROUND & AIMS: Probiotics contain living microorganisms consumed for their putative benefits on the intestinal microbiota and general health and a concept is emerging to use probiotic as a therapeutic intervention to reduce proton pump inhibitors (PPIs) negative effects, but data is lacking. The use of PPIs can result in disordered gut microbiota, leading to a risk of enteric infections. PPIs are frequently prescribed in the general practice setting for gastroesophageal reflux disease (GERD), peptic ulcer disease, and related conditions. Despite the availability and widespread use of probiotics and acid-suppressing medications, the effect of PPIs-induced gastric acid suppression on the survival and colonization of probiotics bacterial species is currently unclear. We hypothesized that gastric acid suppression may improve intestinal colonization of probiotics bacterial species and probiotic intervention may have a potential role in mitigating untoward effects of PPI.METHODS: In a randomized, double-blind, placebo-controlled study, healthy subjects were given either proton pump inhibitor (PPI, n=15) or placebo (n=15) over 6 weeks. All subjects then consumed multi-strain probiotics from weeks 2-6. Thirty participants (10 males, 20 females, age range: 18-56 years) were enrolled in the study. Shotgun metagenomic sequencing and untargeted metabolomics analyses were performed on stool samples collected at week 0, 2, and 6.RESULTS: Short term PPI treatment increased the microbial abundance of Streptococcaceae (p=0.004), Leuconostacaceae (p=0.001), and Pasteurellaceae (p=0.020) at family level and corresponding genus levels. The metabolomic analysis of the stools revealed a change in 10 metabolites where Gly Arg Val and phenylacetic acid were consistently increased compared to the baseline. Probiotic intervention inhibited PPI-induced microbial changes such as a decrease in Leuconostacaceae family (p=0.01) and led to an increase in metabolite 1H-Indole-4-carbaldehyde. Notably, PPI enhanced the colonization of certain probiotic bacterial species like Streptococcus thermophilus (p<0.05) along with other species present in the multi-strain probiotic.CONCLUSION: Acid suppression enhanced certain probiotic associated bacterial colonization and probiotics in turn suppressed PPI-mediated intestinal microbial alterations. Thus, probiotics in combination with PPI might be a beneficial strategy that allows probiotic colonization and suppress PPI-induced microbial perturbations. CLINICAL TRIALS.GOV, NUMBER: NCT03327051.

    View details for DOI 10.1016/j.clnesp.2021.11.005

    View details for PubMedID 35063245

  • Randomized, Double-Blinded, Placebo-Controlled Trial of Simvastatin to Prevent Recurrent Pancreatitis PANCREAS Goodman, M. T., Lo, S. K., Yadav, D., Wu, B. U., Jamil, L. H., Kwok, K. K., Papachristou, G. I., Afghani, E., Choi-Kuaea, Y., Waldron, R. T., Lombardi, C., Jeon, C. Y., Helenowski, I. B., Richmond, E., Benante, K., Habtezion, A., Schering, T., Khan, S. A., Rodriguez, L. M., Pandol, S. J. 2022; 51 (1): E10-E12

    View details for Web of Science ID 000759723600009

    View details for PubMedID 35195610

    View details for PubMedCentralID PMC8887796