A5102796074- RNA modifications and cancer
- Liver Disease Diagnosis and Treatment
- Phagocytosis and Immune Regulation
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Reproductive Biology and Fertility
- Cancer-related gene regulation
- RNA Research and Splicing
- Neonatal Respiratory Health Research
- Medical Imaging and Pathology Studies
- Prostate Cancer Treatment and Research
- Liver physiology and pathology
- Peptidase Inhibition and Analysis
- Pancreatic function and diabetes
- RNA and protein synthesis mechanisms
- Cancer, Hypoxia, and Metabolism
- Cancer-related molecular mechanisms research
- Protease and Inhibitor Mechanisms
The University of Texas Southwestern Medical Center
2021-2024
University of California, San Francisco
2010
University of Pennsylvania
1999
The liver is organized into zones in which hepatocytes express different metabolic enzymes. cells most responsible for repopulation and regeneration remain undefined, because fate mapping has only been performed on a few hepatocyte subsets. Here, 14 murine fate-mapping strains were used to systematically compare distinct subsets of hepatocytes. During homeostasis, from both periportal zone 1 pericentral 3 contracted number, whereas midlobular 2 expanded number. Cells within 2, are sheltered...
Mitochondria are critical for proper organ function and mechanisms to promote mitochondrial health during regeneration would benefit tissue homeostasis. We report that liver regeneration, proliferation is suppressed in electron transport chain (ETC)–dysfunctional hepatocytes due an inability generate acetyl-CoA from peripheral fatty acids through β-oxidation. Alternative modes production pyruvate or acetate the setting of ETC dysfunction. This metabolic inflexibility forces a dependence on...
Hypoxia has long been implicated in the pathogenesis of fibrotic diseases. Aberrantly activated myofibroblasts are primary pathological driver progression, yet how various microenvironmental influences, such as hypoxia, contribute to their sustained activation and differentiation is poorly understood. As a defining feature hypoxia its impact on cellular metabolism, we sought investigate hypoxia-induced metabolic reprogramming affects myofibroblast test preclinical efficacy targeting...
It is unknown which post-transcriptional regulatory mechanisms are required for oncogenic competence. Here, we show that the LIN28 family of RNA-binding proteins (RBPs), facilitate RNA metabolism within ribonucleoprotein networks, essential initiation diverse oncotypes hepatocellular carcinoma (HCC). In HCC models driven by NRASG12V/Tp53, CTNNB1/YAP/Tp53, or AKT/Tp53, mice without Lin28a and Lin28b were markedly impaired in cancer initiation. We biochemically defined an oncofetal regulon 15...
Prostate-specific antigen (PSA), a serine endoprotease with chymotrypsin-like substrate specificity, is marker used widely for detection of prostate cancer and other diseases, catalyzing hydrolysis the gel-forming proteins semenogelins I II, which are synthesized secreted by seminal vesicle. In this study we report use two single-position minilibraries RP-HPLC selection to optimize hexapeptide PSA, spanning positions P3 P3'. PSA has been shown previously prefer tyrosine in position P1...
Chemical modification of RNAs is important for posttranscriptional gene regulation. The METTL3-METTL14 complex generates most N 6 -methyladenosine (m A) modifications in messenger (mRNAs), and dysregulated methyltransferase expression has been linked to cancers. Here we show that a changed sequence context m A can promote oncogenesis. gain-of-function missense mutation from patients with cancer, METTL14 R298P , increases malignant cell growth culture transgenic mice without increasing global...