Overview
My laboratory is interested in understanding the molecular mechanisms of stem cell function in the normal intestine and in colorectal cancer using innovative three-dimensional organoid and in vivo platforms. We demonstrated that high fat diet-induced obesity activates peroxisome proliferator-activated receptor delta (PPARd) signaling in intestinal stem cells and progenitor cells, which increases stem cell regeneration and tumor initiation in the colon. We also pioneered novel orthotopic transplantation and in situ CRISPR/Cas9 gene editing models of colorectal cancer that recapitulate the adenoma-carcinoma-metastasis sequence. Research in the laboratory is focused on three main areas: 1) Immune regulation of the intestinal epithelium and colorectal cancer; 2) The effects of diet-induced obesity on regeneration in the intestine; and 3) analysis of colorectal cancer heterogeneity with single-cell mRNA sequencing and genetically engineered mouse models. The overall goal of this research is to develop new treatment approaches for intestinal diseases such as inflammatory bowel disease and colorectal cancer. I am also a gastroenterologist at Duke University Hospital and the Durham VA Hospital. My clinical interests include colorectal cancer screening and gastrointestinal cancer genetics.
Current Appointments & Affiliations
Assistant Professor of Medicine
·
2019 - Present
Medicine, Gastroenterology,
Medicine
Assistant Professor in Pharmacology and Cancer Biology
·
2020 - Present
Pharmacology & Cancer Biology,
Basic Science Departments
Assistant Professor of Cell Biology
·
2022 - Present
Cell Biology,
Basic Science Departments
Member of the Duke Cancer Institute
·
2019 - Present
Duke Cancer Institute,
Institutes and Centers
Recent Publications
Asparagine synthetase and G-protein coupled estrogen receptor are critical responders to nutrient supply in KRAS mutant colorectal cancer.
Journal Article Int J Cancer · January 1, 2025 Survival differences exist in colorectal cancer (CRC) patients by sex and disease stage. However, the potential molecular mechanism(s) are not well understood. Here we show that asparagine synthetase (ASNS) and G protein-coupled estrogen receptor-1 (GPER1) ... Full text Link to item CiteIntestinal Cyp24a1 regulates vitamin D locally independent of systemic regulation by renal Cyp24a1 in mice.
Journal Article J Clin Invest · December 17, 2024 Vitamin D regulates mineral homeostasis. The most biologically active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D), is synthesized by CYP27B1 from 25-dihydroxyvitamin D (25D) and is inactivated by CYP24A1. Human monogenic diseases and genome-wide ass ... Full text Link to item CiteVagal stimulation ameliorates murine colitis by regulating SUMOylation.
Journal Article Sci Transl Med · November 20, 2024 Inflammatory bowel diseases (IBDs) are chronic debilitating conditions without cure, the etiologies of which are unknown, that shorten the lifespans of 7 million patients worldwide by nearly 10%. Here, we found that decreased autonomic parasympathetic tone ... Full text Link to item CiteRecent Grants
Mitigation of gastrointestinal acute radiation syndrome by promoting clusterin-mediated intestinal regeneration
ResearchCo-Principal Investigator · Awarded by National Institutes of Health · 2024 - 2029Tissue-Specific Regulation and Effects of CYP24A1
ResearchCo Investigator · Awarded by National Institutes of Health · 2023 - 2027Harnessing treatment-induced tumor evolution and collateral sensitivities using a human rectal cancer co-clinical platform
ResearchCollaborator · Awarded by National Cancer Institute · 2022 - 2027View All Grants
Education, Training & Certifications
Boston University, School of Medicine ·
2004
M.D.