A5041536802- DNA Repair Mechanisms
- Cancer, Hypoxia, and Metabolism
- Telomeres, Telomerase, and Senescence
- Phagocytosis and Immune Regulation
- Immunotherapy and Immune Responses
- DNA and Nucleic Acid Chemistry
- Immune Cell Function and Interaction
- Immune cells in cancer
- Colorectal Cancer Treatments and Studies
- Biochemical and Molecular Research
- Cancer, Lipids, and Metabolism
- Cancer Immunotherapy and Biomarkers
- T-cell and B-cell Immunology
- Muscle metabolism and nutrition
- CRISPR and Genetic Engineering
- Retinoids in leukemia and cellular processes
- Chromosomal and Genetic Variations
- Bacterial Genetics and Biotechnology
- Genomics and Chromatin Dynamics
- Chemokine receptors and signaling
- RNA Interference and Gene Delivery
- Cancer therapeutics and mechanisms
- Genetics, Aging, and Longevity in Model Organisms
- Evolution and Genetic Dynamics
- Adenosine and Purinergic Signaling
RGenix (United States)
2013-2021
Corgenix (United States)
2020
Rockefeller University
2008-2013
Howard Hughes Medical Institute
2009-2013
Temple University
2013
Columbia University Irving Medical Center
2007-2009
Cancer Genetics (United States)
2009
Eppendorf (Germany)
2008
Cancer Research Center
2007
Ludwig Cancer Research
2003
In humans, the pathways of memory and effector T cell differentiation remain poorly defined. We have dissected functional properties ex vivo effector-memory (EM) CD45RA-CCR7- lymphocytes present within circulating CD8+ pool healthy individuals. Our studies show that EM cells are heterogeneous subdivided based on differential CD27 CD28 expression into four subsets. EM(1) (CD27+CD28+) EM(4) (CD27-CD28+) express low levels mediators such as granzyme B perforin high CD127/IL-7Ralpha. also a...
Although numerous chemokines act on monocytes, none of them is specific for these cells. Here, we show that breast and kidney–expressed chemokine (BRAK) a highly selective monocyte chemoattractant. Migration efficacy Bordetella pertussis toxin–sensitive Ca2+ mobilization responses to BRAK were strongly enhanced after treatment monocytes with the cyclic AMP–elevating agents prostaglandin E2 forskolin. first monocyte-selective chemokine, as other types blood leukocytes or monocyte-derived...
The telomeric single-strand DNA binding protein protection of telomeres 1 (POT1) protects from rapid degradation in Schizosaccharomyces pombe and has been implicated positive negative telomere length regulation humans. Human POT1 appears to interact with both through direct the 3′ overhanging G-strand interaction TRF1 duplex complex. influence on telomerase activity not studied at molecular level. We show here that negatively effects vitro. find is required for inhibition. Furthermore,...
RGX-202, a small-molecule creatine transporter SLC6A8 inhibitor, suppresses colorectal cancer and modulates human levels.
Abstract Background: Pre-clinical studies identified creatine metabolism to be activated in KRAS mutant metastatic colorectal cancer (CRC) as a mechanism fuel the increased energy demands of RAS tumors. Metastatic colon cells overexpress and subsequently release kinase-B (CKB) into extracellular space, where it phosphorylates generate high metabolite phosphocreatine. Ompenaclid is small molecule inhibitor transporter SLC6A8. Inhibition SLC6A8 by ompenaclid prevents import...
Replication of telomeres requires the action telomerase, semi-conservative replication machinery and stabilization fork during passage through telomeric DNA. Whether vertebrate support initiation has not been experimentally addressed. Using Xenopus cell free extracts we established a system to study within linear DNA substrates. We show binding TRF2 DNA, indicating that exogenous exclusively composed repeats is recognized by shelterin components. Interaction with telomere proteins sufficient...
3095 Background: RGX-104 is a small-molecule LXR agonist that modulates innate immunity via transcriptional activation of the ApoE gene. depletes myeloid derived suppressor cells (MDSCs) and stimulates dendritic (DCs), activating cytotoxic lymphocytes (CTLs) with anti-tumor activity as monotherapy in combination checkpoint blockade murine models. Methods: We are conducting Phase 1 dose escalation expansion study patients refractory solid tumors. Safety, PK, PD, efficacy being assessed....
This review describes the components of Escherichia coli replisome and dynamic process in which they function interact under normal conditions. It also briefly behavior during situations replication fork movement is disturbed, such as when collides with sites DNA damage. E. Pol III was isolated first from a polA mutant strain that lacked relatively abundant I activity. Further biochemical studies, use double strains, revealed to be replicative polymerase essential cell viability. In...
Abstract Background: Colorectal cancer (CRC) is one of the leading causes deaths worldwide with more than 140,000 patients diagnosed and nearly 50,000 annually in U.S. alone. Roughly 60% present locally advanced or distant metastatic disease, liver being a primary site colonization. Creatine metabolism has been implicated colon progression colonization liver. Metastatic cells upregulate release creatine kinase-B (CKB) into extracellular space, where it phosphorylates to generate high-energy...
Abstract MERTK, a receptor tyrosine kinase of the TYRO3/AXL/MERTK (TAM) family, is expressed in innate immune cells including macrophages, dendritic and NK overexpressed wide variety cancers, leukemia many solid cancers. Activation MERTK on cancer via ligand binding results activation several tumor-promoting signaling pathways, which stimulate proliferation, migration angiogenesis, decrease apoptosis chemosensitivity. Furthermore, macrophages drives evasion through promotion an...
3504 Background: About 65% of advanced colorectal cancer (CRC) patients (pts) have creatine kinase B (CKB) expressing tumors. CKB (CKB+) GI cells import via the transporter SLC6a8 and utilize it to generate intracellular ATP. RGX-202, a small molecule inhibitor SLC6a8, reduces ATP levels, leading apoptosis. RGX-202 treatment triggers complete tumor regressions in multiple CKB+ preclinical models, including KRAS mutant CRC. Methods: RGX-202-001 is phase I escalation/expansion study +/-...
Abstract Background: Myeloid epithelial reproductive tyrosine kinase (MERTK), a transmembrane protein receptor from the TAM (Tyro3, Axl, Mertk) family, is overexpressed in cancer and associated with reduced apoptosis chemoresistance, making it an attractive therapeutic target. RGX-019-MMAE, novel humanized IgG1-MMAE antibody-drug conjugate (ADC) (Inspirna, Inc), selectively binds to MERTK high affinity on tumor cells, resulting internalization degradation of receptor. It then induces...
e15103 Background: MERTK, a member of the TAM family receptor tyrosine kinases, is overexpressed in numerous solid and hematologic cancers. MERTK expression has been implicated promoting cellular proliferation, survival drug resistance. also expressed on innate immune cells, predominantly immune-suppressive M2 macrophages, where it mediates phagocytosis apoptotic cells regulates immunosuppressive cytokines. Development inhibitors hampered by observance retinal degeneration due to inhibition...
3579 Background: A proprietary in vivo target discovery screen identified creatine kinase-B (CKB) as a cancer driver KRAS mutant (KRAS-mut) CRC. CKB promotes tumor growth and survival under hypoxia. generates the energetic metabolite phospho-creatine (PCr), which is imported into cells through transporter, SLC6A8. PCr intracellular ATP that enables tumoral survival. RGX-202-01 small molecule inhibitor of SLC6A8 depletes ATP, resulting apoptosis. In completed Phase 1a study, monotherapy...
MERTK, a receptor tyrosine kinase of the TYRO3/AXL/MERTK (TAM) family, is expressed in innate immune cells including macrophages, dendritic and NK overexpressed wide variety cancers, leukemia many solid cancers. Activation MERTK on cancer via ligand binding results activation several tumor-promoting signaling pathways, which stimulate proliferation, migration angiogenesis, decrease apoptosis chemosensitivity. Furthermore, macrophages drives evasion through promotion an immune-suppressive M2...