A5059624887- Renal cell carcinoma treatment
- Epigenetics and DNA Methylation
- Cellular Mechanics and Interactions
- Renal and related cancers
- RNA modifications and cancer
- Genetic and Kidney Cyst Diseases
- Microtubule and mitosis dynamics
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- Neurobiology and Insect Physiology Research
- Protein Degradation and Inhibitors
- Advanced biosensing and bioanalysis techniques
- Hippo pathway signaling and YAP/TAZ
- Immune cells in cancer
- Heat shock proteins research
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- Histone Deacetylase Inhibitors Research
- Biocrusts and Microbial Ecology
- Cancer Immunotherapy and Biomarkers
- Immune Response and Inflammation
- Cancer Genomics and Diagnostics
- Spaceflight effects on biology
- Genomics and Chromatin Dynamics
- 3D Printing in Biomedical Research
Vanderbilt University Medical Center
2017-2025
Nashville Oncology Associates
2025
University School of Nashville
2025
Vanderbilt University
2017-2021
Massachusetts Institute of Technology
2011-2016
Southport College
2014
Duke University
2010-2011
Duke University Hospital
2010
Duke Medical Center
2010
Cancer cells can inhibit effector T (Teff) through both immunomodulatory receptors and the impact of cancer metabolism on tumor microenvironment. Indeed, Teff require high rates glucose metabolism, consumption essential nutrients or generation waste products by may impede cell metabolic pathways. Clear renal carcinoma (ccRCC) is characterized loss suppressor von Hippel-Lindau (VHL) altered metabolism. Here, we assessed how ccRCC influences activation primary patient infiltrating lymphocytes...
During morphogenesis, contraction of the actomyosin cytoskeleton within individual cells drives cell shape changes that fold tissues. Coordination cytoskeletal contractility is mediated by regulating RhoA GTPase activity. Guanine nucleotide exchange factors (GEFs) activate and GTPase-activating proteins (GAPs) inhibit Most studies tissue folding, including apical constriction, have focused on how activated GEFs to promote contractility, with little investigation as GAPs may be important....
Metabolic reprogramming dictates the fate and function of stimulated T cells, yet these pathways can be suppressed in cells tumor microenvironments. We previously showed that glycolytic mitochondrial adaptations directly contribute to reducing effector renal cell carcinoma (RCC) CD8+ tumor-infiltrating lymphocytes (TILs). Here we define role metabolic activation functions RCC TILs. CD28 costimulation plays a key augmenting metabolism, is antagonized by inhibitory checkpoint immunotherapy...
Heat is a cardinal feature of inflammation, yet its impacts on immune cells remain uncertain. We show that moderate-grade fever temperatures (39°C) increased murine CD4 T cell metabolism, proliferation, and inflammatory effector activity while decreasing regulatory suppressive capacity. However, heat-exposed helper 1 (T H 1) selectively developed mitochondrial stress DNA damage activated Trp53 stimulator interferon genes pathways. Although many subjected to such died, surviving exhibited...
Loss of the short arm chromosome 3 (3p) occurs early in >95% clear cell renal carcinoma (ccRCC). Nearly ubiquitous 3p loss ccRCC suggests haploinsufficiency for tumor suppressors as drivers tumorigenesis. We previously reported methyltransferase SETD2, which trimethylates H3 histones on lysine 36 (H3K36me3) and is located deletion, to also trimethylate microtubules 40 (αTubK40me3) during mitosis, with αTubK40me3 required genomic stability. now show that monoallelic, Setd2-deficient cells...
SETD2 regulates actin dynamics and cell migration via methylation of at Lys 68 in a cellular complex containing Huntingtin.
From insects to mice, oocytes develop within cysts alongside nurse-like sister germ cells. Prior fertilization, the nurse cells' cytoplasmic contents are transported into oocyte, which grows as its cells regress and die. Although critical for fertility, biological physical mechanisms underlying this transport process poorly understood. Here, we combined live imaging of germline cysts, genetic perturbations, mathematical modeling investigate dynamics that enable directional complete in
The nonphysiological nutrient levels found in traditional culture media have been shown to affect numerous aspects of cancer cell physiology, including how cells respond certain therapeutic agents. Here, we comprehensively evaluated physiological response by performing drug screening human plasma-like medium. We observed dramatic nutrient-dependent changes sensitivity a variety FDA-approved and clinically trialed compounds, rigosertib, an experimental that recently failed phase III clinical...
The maintenance of rapid and efficient actin dynamics in vivo requires coordination filament assembly disassembly. This regulation temporal spatial integration signaling pathways by protein complexes. However, it remains unclear how these complexes form then regulate the cytoskeleton. Here, we identify a srGAP2 formin-like 1 (FMNL1, also known as FRL1 or FRLα) complex whose is regulated Rac signaling. Our data suggest regulates FMNL1 two ways; 1) Rac-mediated activation leads to recruitment...
The chromatin-associated protein WD Repeat Domain 5 (WDR5) is a promising target for cancer drug discovery, with most efforts blocking an arginine-binding cavity on the called ‘WIN’ site that tethers WDR5 to chromatin. WIN inhibitors (WINi) are active against multiple cell types in vitro, notable of which those derived from MLL-rearranged (MLLr) leukemias. Peptidomimetic WINi were originally proposed inhibit MLLr cells via dysregulation genes connected hematopoietic stem expansion. Our...
Metastasis causes most cancer deaths and reflects transitions from primary tumor escape to seeding growth at metastatic sites. Epithelial-to-mesenchymal transition (EMT) is important early in metastasis enable cells detach neighboring cells, become migratory, the tumor. While different phases of expose variable nutrient environments demands, metabolic requirements plasticity each step are uncertain. Here we show that EMT stimulated by disrupted oxidative metabolism. Using Renal Cell...
Domain-based proteomics analysis identifies binding partners and potential functions for a family of GTPase-activating proteins that regulate the cytoskeleton.
During development, coordinated cell shape changes alter tissue shape. In the Drosophila ventral furrow and other epithelia, apical constriction of hundreds epithelial cells folds tissue. Genes in G α12/13 pathway coordinate collective constriction, but mechanism coordination is poorly understood. Coupling live-cell imaging with a computational approach to identify contractile events, we discovered that differences behavior are biased by initial Disrupting exacerbates this relationship....
Centrosomes play a fundamental role in nucleating and organizing microtubules the cell are vital for faithful chromosome segregation maintenance of genomic stability. Loss structural or functional integrity centrosomes causes instability is driver oncogenesis. The lysine demethylase 4A (KDM4A) an epigenetic 'eraser' chromatin methyl marks, which we show also localizes to centrosome with single molecule resolution. We additionally discovered KDM4A enzymatic activity required maintain...
Post-translational modifications to tubulin are important for many microtubule-based functions inside cells. It was recently shown that methylation of by the histone methyltransferase SETD2 occurs on mitotic spindle microtubules during cell division, with its absence resulting in defects. However, catalytic mechanism methyl addition is unclear. We used a truncated version human wild type (tSETD2) containing SET and C-terminal Set2–Rpb1–interacting (SRI) domains investigate biochemical...
Abstract Aim Deregulated signaling pathways are a hallmark feature of oncogenesis and driver tumor progression. Dual specificity protein phosphatase 4 (DUSP4) is critical negative regulator the mitogen-activated kinase (MAPK) pathway often deleted or epigenetically silenced in tumors. DUSP4 alterations lead to hyperactivation MAPK many cancers, including breast cancer, which harbor mutations cell cycle checkpoint genes, particularly TP53. Methods Using genetically engineered mouse model, we...
F. Mason, Trans. Faraday Soc., 1921, 16, 534 DOI: 10.1039/TF9211600534
ABSTRACT The non-physiological nutrient levels found in traditional culture media have been shown to affect numerous aspects of cancer cell physiology, including how cells respond certain therapeutic agents. Here, we comprehensively evaluated physiological impact response by performing drug screening human plasma-like medium (HPLM). We observed dramatic nutrient-dependent changes sensitivity a variety FDA-approved and clinically trialed compounds, rigosertib, an experimental that has...
Abstract Pharmacological methods for promoting mitochondrial elongation suggest that effector T cells can be altered to support a memory cell–like metabolic state. Such approaches may enhance the development of immunological memory. Therefore, we hypothesized deletion fission protein dynamin-related 1 (DRP1) would lead and generate large cell population, an approach could exploited vaccination protocols. We find that, as expected, while DRP1 from in dLckCre × Drp1flfl does compromise...