Chromospheric Activity of HAT-P-11: an Unusually Active Planet-Hosting K Star

Kepler photometry of the hot Neptune host star HAT-P-11 suggests that its spot latitude distribution is comparable to the Sun's near solar maximum. We search for evidence of an activity cycle in the CaII H & K chromospheric emission $S$-index with archival Keck/HIRES spectra and observations from the echelle spectrograph on the ARC 3.5 m Telescope at APO. The chromospheric emission of HAT-P-11 is consistent with a $\gtrsim 10$ year activity cycle, which plateaued near maximum during the Kepler mission. In the cycle that we observed, the star seemed to spend more time near active maximum than minimum. We compare the $\log R^\prime_{HK}$ normalized chromospheric emission index of HAT-P-11 with other stars. HAT-P-11 has unusually strong chromospheric emission compared to planet-hosting stars of similar effective temperature and rotation period, perhaps due to tides raised by its planet.Comment: 16 pages, 8 figures; accepted to the Astrophysical Journa

IDENTIFY FUNCTIONAL PROTEINS INTERACTING WITH MMSET IN MULTIPLE MYELOMA

Ph.DDOCTOR OF PHILOSOPH

SMARCA2 Is a Novel Interactor of NSD2 and Regulates Prometastatic PTP4A3 through Chromatin Remodeling in t(4;14) Multiple Myeloma

10.1158/0008-5472.CAN-20-2946CANCER RESEARCH8192332-234

NF-kappa B promotes the stem-like properties of leukemia cells by activation of LIN28B

10.4252/wjsc.v10.i4.34WORLD JOURNAL OF STEM CELLS10434-4

A loss-of-function genetic screening reveals synergistic targeting of AKT/mTOR and WTN/β-catenin pathways for treatment of AML with high PRL-3 phosphatase

Abstract Background Protein tyrosine phosphatase of regenerating liver 3 (PRL-3) is overexpressed in a subset of AML patients with inferior prognosis, representing an attractive therapeutic target. However, due to relatively shallow pocket of the catalytic site of PRL-3, it is difficult to develop selective small molecule inhibitor. Methods In this study, we performed whole-genome lentiviral shRNA library screening to discover synthetic lethal target to PRL-3 in AML. We used specific small molecule inhibitors to validate the synthetic lethality in human PRL-3 high vs PRL-3 low human AML cell lines and primary bone marrow cells from AML patients. AML mouse xenograft model was used to examine the in vivo synergism. Results The list of genes depleted in TF1-hPRL3 cells was particularly enriched for members involved in WNT/β-catenin pathway and AKT/mTOR signaling. These findings prompted us to explore the impact of AKT/mTOR signaling inhibition in PRL-3 high AML cells in combination with WNT/β-catenin inhibitor. VS-5584, a novel, highly selective dual PI3K/mTOR inhibitor, and ICG-001, a WNT inhibitor, were used as a combination therapy. A synthetic lethal interaction between mTOR/AKT pathway inhibition and WNT/β-catenin was validated by a variety of cellular assays. Notably, we found that treatment with these two drugs significantly reduced leukemic burden and prolonged survival of mice transplanted with human PRL-3 high AML cells, but not with PRL-3 low AML cells. Conclusions In summary, our results support the existence of cooperative signaling networks between AKT/mTOR and WNT/β-catenin pathways in PRL-3 high AML cells. Simultaneous inhibition of these two pathways could achieve robust clinical efficacy for this subtype of AML patient with high PRL-3 expression and warrant further clinical investigation

Additional file 2: of A loss-of-function genetic screening reveals synergistic targeting of AKT/mTOR and WTN/β-catenin pathways for treatment of AML with high PRL-3 phosphatase

Figure S1. Relative quantification of PTP4A3 (PRL-3) expression level in OCI-AML2 and MOLM-14 cells by qRT-PCR analysis. Figure S2. Representative immunoblot showing the levels of indicated proteins in OCI-AML2 (PRL-3 low) cells with different treatments. Figure S3. In vivo efficacy of VS-5584, ICG-001 single agent and combination treatment in mouse xenograft models transplanted OCI-AML2 cells. (PDF 246 kb

Additional file 1: of A loss-of-function genetic screening reveals synergistic targeting of AKT/mTOR and WTN/β-catenin pathways for treatment of AML with high PRL-3 phosphatase

Table S1. Genes critical for survival of PRL-3 high AML cells revealed by Mission shRNA library screening. (XLS 246 kb

ASLAN003, a potent dihydroorotate dehydrogenase inhibitor for differentiation of acute myeloid leukemia.

10.3324/haematol.2019.230482Haematologica10592286-229