About

Dr. James Fleet is the Margaret McKean Love Endowed Professor in Nutrition, Cellular, and Molecular Sciences at the University of Texas at Austin. He holds a BS and Ph.D. from Cornell University and has held faculty positions at Tufts University, the University of North Carolina at Greensboro, and Purdue University. His research focuses on the molecular and physiological functions of vitamin D, particularly in relation to calcium metabolism and cancer prevention. Dr. Fleet employs molecular biology, genomics, and genetics tools to investigate how vitamin D influences human health and disease, with specific attention to calcium and bone homeostasis and colon cancer prevention. His work has linked calcium absorption to bone mass development during growth and the maintenance of adult bone mass, utilizing mouse genetics to explore genetic variation in calcium and bone metabolism. Additionally, his research evaluates vitamin D's role in modulating innate immunity, macrophage polarization, and its impact on colitis and colon cancer development. Dr. Fleet has published extensively, contributed to establishing academic programs, and received numerous awards, including the Mead Johnson Award from the ASN and recognition as a distinguished professor. His research program extensively uses genomic tools such as RNA-seq, ATAC-seq, ChIP-seq, and single-cell RNA-seq to understand gene regulation mechanisms by vitamin D.

Research topics

• Biology
• Internal medicine
• Endocrinology
• Cell biology
• Medicine
• Biochemistry
• Chemistry
• Genetics
• Computational biology

Selected publications

• Vitamin D-Mediated Regulation of Intestinal Calcium Absorption

  Nutrients · 2022 · 137 citations

  1st authorCorresponding
  • Endocrinology
  • Internal medicine
  • Chemistry

  D), a hormone that activates gene transcription following binding to the intestinal vitamin D receptor (VDR). When dietary Ca intake is low, Ca absorption follows a vitamin-D-regulated, saturable pathway, but when dietary Ca intake is high, Ca absorption is predominately through a paracellular diffusion pathway. Deletion of genes that mediate vitamin D action (i.e., VDR) or production (CYP27B1) eliminates basal Ca absorption and prevents the adaptation of mice to low-Ca diets. Various physiologic or disease states modify vitamin-D-regulated intestinal absorption of Ca (enhanced during late pregnancy, reduced due to menopause and aging).

  DOI

• Drivers of transcriptional variance in human intestinal epithelial organoids

  Physiological Genomics · 2021 · 40 citations

  • Biology
  • Cell biology
  • Computational biology

  Human intestinal epithelial organoids (enteroids and colonoids) are tissue cultures used for understanding the physiology of the human intestinal epithelium. Here, we explored the effect on the transcriptome of common variations in culture methods, including extracellular matrix substrate, format, tissue segment, differentiation status, and patient heterogeneity. RNA-sequencing datasets from 276 experiments performed on 37 human enteroid and colonoid lines from 29 patients were aggregated from several groups in the Texas Medical Center. DESeq2 and gene set enrichment analysis (GSEA) were used to identify differentially expressed genes and enriched pathways. PERMANOVA, Pearson's correlation, and dendrogram analysis of the data originally indicated three tiers of influence of culture methods on transcriptomic variation: substrate (collagen vs. Matrigel) and format (3-D, transwell, and monolayer) had the largest effect; segment of origin (duodenum, jejunum, ileum, colon) and differentiation status had a moderate effect; and patient heterogeneity and specific experimental manipulations (e.g., pathogen infection) had the smallest effect. GSEA identified hundreds of pathways that varied between culture methods, such as IL1 cytokine signaling enriched in transwell versus monolayer cultures and E2F target genes enriched in collagen versus Matrigel cultures. The transcriptional influence of the format was furthermore validated in a synchronized experiment performed with various format-substrate combinations. Surprisingly, large differences in organoid transcriptome were driven by variations in culture methods such as format, whereas experimental manipulations such as infection had modest effects. These results show that common variations in culture conditions can have large effects on intestinal organoids and should be accounted for when designing experiments and comparing results between laboratories. Our data constitute the largest RNA-seq dataset interrogating human intestinal epithelial organoids.

  DOI

• Analysis of 1,25-Dihydroxyvitamin D₃ Genomic Action Reveals Calcium-Regulating and Calcium-Independent Effects in Mouse Intestine and Human Enteroids

  Molecular and Cellular Biology · 2020 · 20 citations

  • Biology
  • Internal medicine
  • Endocrinology

  in the intestine was observed. Our findings suggest an interrelationship between vitamin D and intestinal Mn efflux and indicate the importance of distal intestinal segments to vitamin D action.

  DOI

Recent grants

• NIH Grant R01CA101113

  NIH · $1.9M · 2010

• Nutrigenomics of Intestinal Vitamin D Action

  NIH · $4.2M · 2017–2028

• NIH Grant R21CA165240

  NIH · $315k · 2015

• NIH Grant R21ES019103

  NIH · $752k · 2012

• NIH Grant R01DK054111

  NIH · $3.5M · 2013

Frequent coauthors

• Steven K. Clinton

  The Ohio State University

  31 shared

• Richard J. Wood

  Nationwide Children's Hospital

  27 shared

• Pavlo L. Kovalenko

  27 shared

• Jun‐Ge Yu

  21 shared

• Sylvia Christakos

  Rutgers, The State University of New Jersey

  21 shared

• Sophia L. Maund

  20 shared

• Andrew Thorburn

  University of Colorado Anschutz Medical Campus

  20 shared

• Jason Hipp

  Mayo Clinic in Arizona

  20 shared

Education

• Ph.D., Division of Nutrition

  Cornell University

  1988

Awards & honors

• Mead Johnson Award from the ASN (2001)
• University Faculty Scholar (2004-9)
• distinguished professor at Purdue
• fellow of the American Society for Bone and Mineral Research…

Similar researchers at University of Texas at Austin

• Carlos Caldash-218
• Thomas J. Hughesh-154
• George Georgiouh-107
• Keith Johnstonh-106
• Jeffrey Andrewsh-104