Derek A. Franklin
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DEVELOPMENT AND CHARACTERIZATION OF SL-325, A DR3-TARGETED, ANTAGONISTIC ANTIBODY FOR THE TREATMENT OF IBD Open
BACKGROUND Commonly known as Death Receptor 3 (DR3), tumor necrosis factor receptor super family 25 (TNFRSF25) is a member of the TNFR super family that binds to soluble and cell-surface expressed forms of its monogamous ligand, TL1A. Dysr…
DOP033 Pre-Clinical Development of SL-325, a High Affinity DR3 Blocking Antibody, for Durable Blockade of the DR3/TL1A Axis in Inflammatory Bowel Disease Open
Background TL1A blocking antibodies have demonstrated promising clinical remission rates in patients with inflammatory bowel disease (Sands B et al, NEJM 2024). TL1A promotes inflammation through binding to a single receptor, DR3. There ar…
Carnitine o-octanoyltransferase is a p53 target that promotes oxidative metabolism and cell survival following nutrient starvation Open
Whereas it is known that p53 broadly regulates cell metabolism, the specific activities that mediate this regulation remain partially understood. Here, we identified carnitine o-octanoyltransferase (CROT) as a p53 transactivation target th…
1203 Antigen targeted butyrophilin heterodimer-based bispecific engagers induce Vγ9δ2<sup>+</sup> T cell-mediated anti-tumor activity Open
Background Decreased antigen expression and antigen presentation via major histocompatibility complexes (MHCs) evades αβ T cell recognition. γδ T cells recognize stressed cells in an MHC-independent manner, and consequently, may be exploit…
Pyrimidine Nucleotides with 4-Alkyloxyimino and Terminal Tetraphosphate δ-Ester Modifications as Selective Agonists of the P2Y 4 Receptor Open
P2Y2 and P2Y4 receptors are G protein-coupled receptors, activated by UTP and dinucleoside tetraphosphates, which are difficult to distinguish pharmacologically for lack of potent and selective ligands. We varied structurally phosphate and…
MDM2-p53 Pathway in Hepatocellular Carcinoma Open
Abnormalities in the TP53 gene and overexpression of MDM2, a transcriptional target and negative regulator of p53, are commonly observed in cancers. The MDM2-p53 feedback loop plays an important role in tumor progression and thus, increase…
MEK activation modulates glycolysis and supports suppressive myeloid cells in TNBC Open
Triple-negative breast cancers (TNBCs) are heterogeneous and aggressive, with high mortality rates. TNBCs frequently respond to chemotherapy, yet many patients develop chemoresistance. The molecular basis and roles for tumor cell-stromal c…
p53 coordinates DNA repair with nucleotide synthesis by suppressing PFKFB3 expression and promoting the pentose phosphate pathway Open
Activation of p53 in response to DNA damage is essential for tumor suppression. Although previous studies have emphasized the importance of p53-dependent cell cycle arrest and apoptosis for tumor suppression, recent studies have suggested …
View article: p53 upregulates PLCε-IP3-Ca2+ pathway and inhibits autophagy through its target gene Rap2B
p53 upregulates PLCε-IP3-Ca2+ pathway and inhibits autophagy through its target gene Rap2B Open
The tumor suppressor p53 plays a pivotal role in numerous cellular responses as it regulates cell proliferation, metabolism, cellular growth, and autophagy. In order to identify novel p53 target genes, we utilized an unbiased microarray ap…
Protection against High-Fat-Diet-Induced Obesity in MDM2 C305F Mice Due to Reduced p53 Activity and Enhanced Energy Expenditure Open
The RPL11-MDM2 interaction constitutes a p53 signaling pathway activated by deregulated ribosomal biosynthesis in response to stress. Mice bearing an MDM2C305F mutation that disrupts RPL11-MDM2 binding were analyzed on a high-fat diet (HFD…
Synthesis and Optimization of New 3,6-Disubstitutedindole Derivatives and Their Evaluation as Anticancer Agents Targeting the MDM2/MDM<i>x</i> Complex Open
Twelve derivatives of the general formula 3-substituted-6-chloroindoles were synthesized and tested for their growth inhibitory effects versus p53(+/+) colorectal cancer HCT116 and its p53 knockout isogenic cells; colorectal cancer cell p5…
MEK inhibition activates STAT signaling to increase breast cancer immunogenicity via MHC-I expression Open
These findings suggest that MAPK signaling and STAT activation are inversely related in both mouse and human mammary tumors. This work also supports further study of MEKi to increase STAT signaling and potentially, immunotherapy responses …
Exploring the Metabolic Regulation of p53 from Ribosomal Proteins to Very Long Chain Fatty Acids Open
The tumor suppressor p53 is the most well-studied gene in biology. The majority of studies have focused on the ability of p53 to control cell cycle arrest, cellular senescence, and apoptosis. Surprisingly, recent studies in mice that retai…
View article: p53 upregulates PLCε-IP3-Ca2+ pathway and inhibits autophagy through its target gene Rap2B
p53 upregulates PLCε-IP3-Ca2+ pathway and inhibits autophagy through its target gene Rap2B Open
The tumor suppressor p53 plays a pivotal role in numerous cellular responses as it regulates cell proliferation, metabolism, cellular growth, and autophagy. In order to identify novel p53 target genes, we utilized an unbiased microarray ap…
Nutrient availability dictates the regulation of metabolism by the ribosomal protein-MDM2-p53 pathway Open
Nutrient availability alters ribosomal biogenesis, causing ribosomal proteins to act as secondary messengers of nutrient response by binding to MDM2 and activating p53. Recent work suggests that the ribosomal protein (RP)-MDM2-p53 pathway …
Protection against High-Fat-Diet-Induced Obesity in MDM2C305F Mice Due to Reduced p53 Activity and Enhanced Energy Expenditure Open
The RPL11-MDM2 interaction constitutes a p53 signaling pathway activated by deregulated ribosomal biosynthesis in response to stress. Mice bearing an MDM2C305F mutation that disrupts RPL11-MDM2 binding were analyzed on a high-fat diet (HFD…
The Evolution of the Ribosomal Protein–MDM2–p53 Pathway Open
The progression of our understanding of ribosomal proteins as static building blocks of the ribosome to highly integrated sensors of p53 surveillance and function has achieved a tremendous rate of growth over the past several decades. As t…