I enjoy working with a multidisciplinary team to care for patients who have complex medical needs with the aim of giving children a better future. As a clinical researcher, my main focus is on finding improved therapies for autoimmune and cholestatic liver diseases, since an ideal therapy currently does not exist.
- Pediatric Gastroenterology
- Transplant Hepatology
Clinical Assistant Professor, Pediatrics - Gastroenterology
Honors & Awards
Studies in Pediatric Liver Transplant Grant Recipient, SPLIT (2017)
Fellow Symposium Grant Recipient, AST (2016)
Award for Excellence in Quality Improvement, TTHSC (2015)
Resident of The Year Award, TTHSC (2014)
Resident of The Year Award, TTHSC (2013)
Boards, Advisory Committees, Professional Organizations
Member, SPLIT (2018 - Present)
Member, AASLD (2017 - Present)
Member, NASPGHAN (2014 - Present)
Board Certification: American Board of Pediatrics, Transplant Hepatology (2020)
Fellowship: UCSF Pediatric Transplant Hepatology (2019) CA
Board Certification, Pediatric Gastroenterology (2019)
Fellowship: Yale University Pediatric Gastroenterology Fellowship (2018) CT
Board Certification: American Board of Pediatrics, Pediatrics (2015)
Residency: Texas Tech University Pediatric Residency (2015) TX
Medical Education: Royal College of Surgeons In Ireland School of Medicine (2010) Ireland
Letter to the editor: Oral vancomycin versus no therapy for pediatric primary sclerosing cholangitis.
Hepatology (Baltimore, Md.)
In their recent study addressing efficacy oforal vancomycin (OVT) and ursodeoxycholic acid (UDCA) compared to no therapy in pediatric primary sclerosing cholangitis (PSC),Deneau et al.state: "OVT and UDCA are not effective treatments for PSC in children" . Their study shows that the null hypothesis of no effect has not been rejected; a real effect might have been present but missed. Complications take up to 10 years to develop, but their median follow-up was just 4.2 years. The subsequent editorial  noted the limitations of a retrospective, propensity-matched study and argues cogently for the need to replace empiric practice with data from well-planned randomized controlled trials (RCTs).
View details for DOI 10.1002/hep.31764
View details for PubMedID 33638221
SARS-CoV2 Infection in Children with Liver Transplant and Native Liver Disease: An International Observational Registry Study.
Journal of pediatric gastroenterology and nutrition
Increased mortality risk due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) infection in adults with native liver disease (LD) and liver transplant (LT) is associated with advanced age and comorbid conditions. We aim to report outcomes for children with LD and LT enrolled in the NASPGHAN/SPLIT SARS-CoV2 registry.In this multicenter observational cohort study, we collected data from 91 patients <21 years (LD 44, LT 47) with laboratory-confirmed SARS-CoV2 infection between April 21 and September 17, 2020.Patients with LD were more likely to require admission (70% vs 43% LT, p = 0.007) and pediatric intensive care unit (PICU) management (32% vs 4% LT, p = 0.001). Seven LD patients required mechanical ventilation (MV) and 2 patients died; no patients in the LT cohort died or required MV. Four LD patients presented in pediatric acute liver failure (PALF), 2 with concurrent multisystem inflammatory syndrome in children (MIS-C); all recovered without LT. Two LD patients had MIS-C alone and one patient died. Bivariable logistic-regression analysis found that patients with non-alcoholic fatty liver disease (NAFLD) (OR 5.6, p = 0.02) and LD (OR 6.1, p = 0.01, vs LT) had higher odds of severe disease (PICU, vasopressor support, MV, renal replacement therapy or death).Although not directly comparable, LT recipients had lower odds of severe SARS-CoV2 infection (vs LD), despite immunosuppression burden. NAFLD patients reported to the registry had higher odds of severe SARS-CoV2 disease. Future controlled studies are needed to evaluate effective treatments and further stratify LD and LT patients with SARS-CoV2 infection.
View details for DOI 10.1097/MPG.0000000000003077
View details for PubMedID 33605666
Successful response of primary sclerosing cholangitis and associated ulcerative colitis to oral vancomycin may depend on brand and personalized dose: report in an adolescent.
Clinical journal of gastroenterology
Primary sclerosing cholangitis (PSC) is a rare, progressive liver disease characterized by cholestasis and bile duct fibrosis that has no accepted therapy known to delay or arrest its progression. We report a 23-year-old female patient who at age 14 was diagnosed with moderate pancolonic ulcerative colitis (UC) and at age 15 with small-duct PSC unresponsive to conventional therapy. The patient began single drug therapy with the antibiotic oral vancomycin (OVT) and achieved normalization of liver enzymes and resolution of UC symptoms with colonic mucosal healing. These improvements have persisted over 8years. There has been no colon dysplasia, liver fibrosis or failure, bile duct stricture, or cancer. Of note, the patient's response was dependent on the brand of oral vancomycin capsule, as well as dose. This raised the questions of possible differences in bioequivalence of different commercial versions of the drug and whether this factor might play into the variability of efficacy seen in published trials. Evidence suggests that oral vancomycin both alters the intestinal microbiome and has immunomodulatory effects. Its striking effectiveness in this and other patients supports further investigation in randomized trials, with careful attention to its bioavailability profile in the gut.
View details for DOI 10.1007/s12328-020-01296-0
View details for PubMedID 33231850
Open-label prospective therapeutic clinical trials: oral vancomycin in children and adults with primary sclerosing cholangitis.
Scandinavian journal of gastroenterology
BACKGROUND: Oral vancomycin (OV) in primary sclerosing cholangitis (PSC) has been evaluated as a potential therapeutic agent. We report the long-term biochemical course and outcomes of patients with PSC treated with OV.METHODS: Patients were enrolled in 2 open-label clinical trials (ClinicalTrials.gov Identifier: NCT01802073 and NCT01322386) and offered OV at 50mg/kg/day in 3 divided doses if weight <30kg, and 500mg 3 times/day if weight ≥30kg. Patients with biliary strictures requiring stenting or awaiting liver transplant were excluded. Liver biochemistry, MRCP and histology were documented at baseline and while on OV. The primary outcome was a decrease in elevated gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), and/or alanine aminotransferase (ALT) from baseline.RESULTS: 30 subjects were enrolled, and 29 additional subjects who learned of the clinical trial requested OV (total n=59; median age was 13.5years [range, 1.5-44years]; 64.4% were male; and 94.9% had inflammatory bowel disease [IBD]). The median treatment duration was 2.7years (range, 0.2-14years). Ninety-six percent (57/59), 81.3% (48/59), and 94.9% (56/59) experienced reduction of GGT, ALP, and ALT, respectively. Furthermore, 39% (23/59), 22% (13/59), and 55.9% (33/59) experienced normalization of GGT, ALP, and ALT, respectively, within the first 6months of OV treatment. One patient underwent liver transplantation 8years after beginning OV treatment, and one developed biliary strictures requiring endoscopic intervention. OV was well-tolerated by patients, and no patient developed treatment-related adverse events.CONCLUSION: In PSC, OV was well-tolerated and was associated with improvement in liver chemistry. A randomized placebo-controlled clinical trial is warranted.
View details for DOI 10.1080/00365521.2020.1787501
View details for PubMedID 32633158
Bile-Derived Organoids From Patients With Primary Sclerosing Cholangitis Recapitulate Their Inflammatory Immune Profile.
Hepatology (Baltimore, Md.)
2019; 70 (3): 871–82
Primary sclerosing cholangitis (PSC) is a heterogeneous and progressive fibroinflammatory cholangiopathy with no known etiology or effective treatment. Studies of PSC are limited due to difficulty in accessing the cholangiocyte, the small percentage of these cells in the liver, instability of in vitro culture systems, and reliance on samples from end-stage disease. Here, we demonstrate that stem cells can be isolated from the bile of PSC patients undergoing endoscopic retrograde cholangiopancreatography earlier in their clinical course and maintained long term in vitro as three-dimensional (3D) organoids that express a biliary genetic phenotype. Additionally, bile-derived organoids (BDOs) can be biobanked and samples obtained longitudinally over the course of the disease. These BDOs express known cholangiocyte markers including gamma glutamyl transferase, cytokeratin 19, epithelial cellular adhesion molecule, cystic fibrosis transmembrane conductance regulator, and anion exchanger 2. RNA sequence analysis identified 39 genes whose expression differed in organoids from PSC patients compared to non-PSC controls, including human leukocyte antigen DM alpha chain and chemokine (C-C motif) ligand 20 (CCL20), immune-related genes previously described in genome-wide association studies of PSC. Incubation of these BDOs with interleukin 17A or tumor necrosis factor alpha led to an immune-reactive phenotype with a significant increase in secretion of proinflammatory mediators, including CCL20, a T-cell chemoattractant. Conclusion: This study demonstrates that bile can be used as a source of biliary-like cells that can be maintained long term in vitro as 3D organoids; these BDOs retain features of cholangiopathies, including the ability to react to inflammatory stimuli by secreting chemokines and propagating an immune-reactive phenotype reflective of the pathogenesis of these diseases; thus, BDOs represent a platform for the study of the pathogenesis and therapy of cholangiopathies, particularly PSC.
View details for DOI 10.1002/hep.30470
View details for PubMedID 30561836
- Refractory Infantile Chronic Diarrhea and Failure to Thrive in a 6-Month-Old Boy With a Complex Past Medical History CLINICAL PEDIATRICS 2019; 58 (6): 707–10
Bile-Derived Organoids from PSC Patients Recapitulate the Inflammatory Immune Profile Seen in Cholangiopathies, Providing an in Vitro Model to Test Candidate Therapeutic Agents.
WILEY. 2018: 1080A
View details for Web of Science ID 000446020503126
Mindfulness-Based Stress Reduction Improves Stress, Disease Activity and Cytokine Levels in Patients with Autoimmune Hepatitis (AIH)
WILEY. 2018: 1119A–1120A
View details for Web of Science ID 000446020503191
Assessment of Community Pediatric Providers' Approach to a Child With Celiac Disease and Available Serological Testing Associated With a Large Tertiary Care Center
2018; 57 (10): 1199–1203
An evidence-practice gap for use of celiac disease testing can lead to poor resource utilization. False positive tests may lead to unnecessary diet changes, gastroenterology consults, parental/patient concern, and additional testing and expenses complicated by varied available celiac bundles. An understanding of pediatric provider practices according to guideline recommendations further improves this gap.
View details for DOI 10.1177/0009922818769453
View details for Web of Science ID 000440685200009
View details for PubMedID 29667919
Biliary drainage as treatment for allograft steatosis following liver transplantation for PFIC-1 disease: A single-center experience
2018; 22 (4): e13184
Development of macrovesicular steatosis post-LT in patients with PFIC-1 is increasingly being observed, with the etiology not fully understood. We highlight successful and effective EBD for reversal of allograft steatosis in 2 patients with PFIC-1 disease and discuss our experience with internal biliary diversion in this patient population.
View details for DOI 10.1111/petr.13184
View details for Web of Science ID 000433590800014
View details for PubMedID 29654655
Human bile contains stem cells which can be cultured in vitro as 3D organoids.
WILEY. 2017: 64A
View details for Web of Science ID 000412089800110
Diet-Induced Obesity Promotes Colon Tumor Development in Azoxymethane-Treated Mice
2013; 8 (4): e60939
Obesity is an important risk factor for colon cancer in humans, and numerous studies have shown that a high fat diet enhances colon cancer development. As both increased adiposity and high fat diet can promote tumorigenesis, we examined the effect of diet-induced obesity, without ongoing high fat diet, on colon tumor development. C57BL/6J male mice were fed regular chow or high fat diet for 8 weeks. Diets were either maintained or switched resulting in four experimental groups: regular chow (R), high fat diet (H), regular chow switched to high fat diet (RH), and high fat diet switched to regular chow (HR). Mice were then administered azoxymethane to induce colon tumors. Tumor incidence and multiplicity were dramatically smaller in the R group relative to all groups that received high fat diet at any point. The effect of obesity on colon tumors could not be explained by differences in aberrant crypt foci number. Moreover, diet did not alter colonic expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, interleukin-1β, and interferon-γ, which were measured immediately after azoxymethane treatment. Crypt apoptosis and proliferation, which were measured at the same time, were increased in the HR relative to all other groups. Our results suggest that factors associated with obesity - independently of ongoing high fat diet and obesity - promote tumor development because HR group animals had significantly more tumors than R group, and these mice were fed the same regular chow throughout the entire carcinogenic period. Moreover, there was no difference in the number of aberrant crypt foci between these groups, and thus the effect of obesity appears to be on subsequent stages of tumor development when early preneoplastic lesions transition into adenomas.
View details for DOI 10.1371/journal.pone.0060939
View details for Web of Science ID 000318840100109
View details for PubMedID 23560112
View details for PubMedCentralID PMC3616169
The neurotensin receptor-1 promotes tumor development in a sporadic but not an inflammation-associated mouse model of colon cancer
INTERNATIONAL JOURNAL OF CANCER
2012; 130 (8): 1798–1805
Neurotensin receptor-1 (NTR-1) is overexpressed in colon cancers and colon cancer cell lines. Signaling through this receptor stimulates proliferation of colonocyte-derived cell lines and promotes inflammation and mucosal healing in animal models of colitis. Given the causal role of this signaling pathway in mediating colitis and the importance of inflammation in cancer development, we tested the effects of NTR-1 in mouse models of inflammation-associated and sporadic colon cancer using NTR-1-deficient (Ntsr1(-) (/-)) and wild-type (Ntsr1(+/+)) mice. In mice treated with azoxymethane (AOM) to model sporadic cancer, NTR-1 had a significant effect on tumor development with Ntsr1(+/+) mice developing over twofold more tumors than Ntsr1(-) (/-) mice (p = 0.04). There was no effect of NTR-1 on the number of aberrant crypt foci or tumor size, suggesting that NT/NTR-1 signaling promotes the conversion of precancerous cells to adenomas. Interestingly, NTR-1 status did not affect tumor development in an inflammation-associated cancer model where mice were treated with AOM followed by two cycles of 5% dextran sulfate sodium (DSS). In addition, colonic molecular and histopathologic analyses were performed shortly after a single cycle of DSS. NTR-1 status did not affect colonic myeloperoxidase activity or histopathologic scores for damage and inflammation. However, Ntsr1(-) (/-) mice were more resistant to DSS-induced mortality (p = 0.01) and had over twofold higher colonic expression levels of Il6 and Cxcl2 (p < 0.04), cytokines known to promote tumor development. These results represent the first direct demonstration that targeted disruption of the Ntsr1 gene reduces susceptibility to colon tumorigenesis.
View details for DOI 10.1002/ijc.26208
View details for Web of Science ID 000300692300009
View details for PubMedID 21630261
View details for PubMedCentralID PMC3288327
Obesity in the Absence of High Fat Diet Enhances Tumor Development in AOM-Treated Mice
W B SAUNDERS CO-ELSEVIER INC. 2011: S818
View details for Web of Science ID 000290167303612