David J. Waxman

About

David J. Waxman is a Professor of Biology, Medicine, and Biomedical Engineering at Boston University, with a PhD from Harvard University. His research program encompasses three major projects focused on understanding gene regulation and epigenetic mechanisms in mammalian tissues. His work investigates how hormone regulatory circuits, epigenetic modifiers, and long non-coding RNA genes interact to regulate complex gene expression patterns, particularly in the liver, and how environmental chemicals influence these processes, leading to developmental and adult diseases such as fatty liver disease, NASH, and hepatocellular carcinoma. Additionally, Waxman explores cancer therapy, specifically how host-tumor interactions and immune responses can be modulated through novel treatment schedules like metronomic chemotherapy to activate innate immune signaling pathways and improve therapeutic outcomes. His research employs advanced sequencing technologies, bioinformatics analysis, and in vivo models to elucidate regulatory networks, epigenetic states, and mechanisms underlying sex differences in liver gene expression, as well as the impact of environmental exposures on developmental and disease processes.

Research topics

• Biology
• Medicine
• Internal medicine
• Genetics
• Cancer research
• Chemistry
• Artificial Intelligence
• Endocrinology
• Computer Science
• Biochemistry

Selected publications

• Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting

  Nature Communications · 2020 · 101 citations

  Exploring the molecular mechanisms that prevent inflammation during caloric restriction may yield promising therapeutic targets. During fasting, activation of the nuclear receptor peroxisome proliferator-activated receptor α (PPARα) promotes the utilization of lipids as an energy source. Herein, we show that ligand activation of PPARα directly upregulates the long non-coding RNA gene Gm15441 through PPARα binding sites within its promoter. Gm15441 expression suppresses its antisense transcript,…

  DOI

• MAnorm2 for quantitatively comparing groups of ChIP-seq samples

  Genome Research · 2020 · 75 citations

  Eukaryotic gene transcription is regulated by a large cohort of chromatin-associated proteins, and inferring their differential binding sites between cellular contexts requires a rigorous comparison of the corresponding ChIP-seq data. We present MAnorm2, a new computational tool for quantitatively comparing groups of ChIP-seq samples. MAnorm2 uses a hierarchical strategy for normalization of ChIP-seq data and assesses within-group variability of ChIP-seq signals based on an empirical Bayes frame…

  DOI

• Sex-biased genetic programs in liver metabolism and liver fibrosis are controlled by EZH1 and EZH2

  PLoS Genetics · 2020 · 71 citations

  Senior authorCorresponding

  Sex differences in the incidence and progression of many liver diseases, including liver fibrosis and hepatocellular carcinoma, are associated with sex-biased hepatic expression of hundreds of genes. This sexual dimorphism is largely determined by the sex-specific pattern of pituitary growth hormone secretion, which controls a transcriptional regulatory network operative in the context of sex-biased and growth hormone-regulated chromatin states. Histone H3K27-trimethylation yields a major sex-bi…

  DOI

• Liver-specific actions of GH and IGF1 that protect against MASLD

  Nature Reviews Endocrinology · 2024-09-25 · 30 citations

  reviewSenior author
  PublisherDOI

• Plasma growth hormone pulses induce male-biased pulsatile chromatin opening and epigenetic regulation in adult mouse liver

  eLife · 2023-10-24 · 12 citations

  articleOpen accessSenior author

  Sex differences in plasma growth hormone (GH) profiles, pulsatile in males and persistent in females, regulate sex differences in hepatic STAT5 activation linked to sex differences in gene expression and liver disease susceptibility, but little is understood about the fundamental underlying, GH pattern-dependent regulatory mechanisms. Here, DNase-I hypersensitivity site (DHS) analysis of liver chromatin accessibility in a cohort of 18 individual male mice established that the endogenous male rhy…

  PublisherDOI

Recent grants

• Xenobiotic-responsive hepatic long non-coding RNAs

  NIH · $4.6M · 2014–2026

• Regulation of sex differences in liver metabolism

  NIH · $206k · 1999–2019

• NIH Grant RC1ES018332

  NIH · $892k · 2012

Frequent coauthors

• D P Lapenson

  112 shared

• Frank J. Gonzalez

  Colciencias

  98 shared

• Gert Kreibich

  New York University

  62 shared

• Ai‐Ming Yu

  50 shared

• Chong-Sheng Chen

  50 shared

• Kristopher W. Krausz

  50 shared

• Connie Cheung

  Westmead Institute for Medical Research

  49 shared

• Robert J. Edwards

  Harvard University

  49 shared

Similar researchers at Boston University

• Jerry Chenh-96
• Richard B. Primackh-83
• Thomas Gilmoreh-61