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kyle r salci

Allison L Boyd, Jennifer C Reid, Kyle R Salci, Lili Aslostovar, Yannick D Benoit, Zoya Shapovalova, Mio Nakanishi, Deanna P Porras, Mohammed Almakadi, Clinton J V Campbell, Michael F Jackson, Catherine A Ross, Ronan Foley, Brian Leber, David S Allan, Mitchell Sabloff, Anargyros Xenocostas, Tony J Collins, Mickie Bhatia
Acute myeloid leukaemia (AML) is distinguished by the generation of dysfunctional leukaemic blasts, and patients characteristically suffer from fatal infections and anaemia due to insufficient normal myelo-erythropoiesis. Direct physical crowding of bone marrow (BM) by accumulating leukaemic cells does not fully account for this haematopoietic failure. Here, analyses from AML patients were applied to both in vitro co-culture platforms and in vivo xenograft modelling, revealing that human AML disease specifically disrupts the adipocytic niche in BM...
November 2017: Nature Cell Biology
Jong-Hee Lee, Kyle R Salci, Jennifer C Reid, Luca Orlando, Borko Tanasijevic, Zoya Shapovalova, Mickie Bhatia
Induced pluripotent stem cell reprogramming has provided critical insights into disease processes by modeling the genetics and related clinical pathophysiology. Human cancer represents highly diverse genetics, as well as inter- and intra-patient heterogeneity, where cellular model systems capable of capturing this disease complexity would be invaluable. Acute myeloid leukemia (AML) represents one of most heterogeneous cancers and has been divided into genetic subtypes correlated with unique risk stratification over the decades...
July 31, 2017: Stem Cells
Yannick D Benoit, Ryan R Mitchell, Ruth M Risueño, Luca Orlando, Borko Tanasijevic, Allison L Boyd, Lili Aslostovar, Kyle R Salci, Zoya Shapovalova, Jennifer Russell, Masakatsu Eguchi, Diana Golubeva, Monica Graham, Anargyros Xenocostas, Michael R Trus, Ronan Foley, Brian Leber, Tony J Collins, Mickie Bhatia
Targeting of human cancer stem cells (CSCs) requires the identification of vulnerabilities unique to CSCs versus healthy resident stem cells (SCs). Unfortunately, dysregulated pathways that support transformed CSCs, such as Wnt/β-catenin signaling, are also critical regulators of healthy SCs. Using the ICG-001 and CWP family of small molecules, we reveal Sam68 as a previously unappreciated modulator of Wnt/β-catenin signaling within CSCs. Disruption of CBP-β-catenin interaction via ICG-001/CWP induces the formation of a Sam68-CBP complex in CSCs that alters Wnt signaling toward apoptosis and differentiation induction...
July 20, 2017: Cell Chemical Biology
Kyle R Salci, Jung Bok Lee, Ryan R Mitchell, Luca Orlando, Aline Fiebig-Comyn, Zoya Shapovalova, Mickie Bhatia
The combination of OCT4 expression and short-term exposure to reprogramming media induces a state of transcriptional plasticity in human fibroblasts, capable of responding to changes in the extracellular environment. Here we provide characterization of iPSCs established through continued culture of OCT4-induced plastic human fibroblasts in pluripotent-supportive reprogramming media. Human iPSC(OCT4) are morphologically indistinguishable from conventionally derived iPSCs and express core proteins involved in maintenance of pluripotency...
July 2015: Stem Cell Research
Kyle R Salci, Jung Bok Lee, Ryan R Mitchell, Luca Orlando, Aline Fiebig-Comyn, Zoya Shapovalova, Mickie Bhatia
The combination of OCT4 expression and short-term exposure to reprogramming media induces a state of transcriptional plasticity in human fibroblasts, capable of responding to changes in the extracellular environment that facilitate direct cell fate conversion toward lineage specific progenitors. Here we reveal that continued exposure of OCT4-induced plastic human fibroblasts to reprogramming media (RM) is sufficient to induce pluripotency. OCT4-derived induced pluripotent stem cell (iPSC(OCT4)) colonies emerged after prolonged culture in RM, and formed independently of lineage specific progenitors...
July 2015: Stem Cell Research
Kyle R Salci, Jong-Hee Lee, Sarah Laronde, Steve Dingwall, Rahul Kushwah, Aline Fiebig-Comyn, Brian Leber, Ronan Foley, Arianna Dal Cin, Mickie Bhatia
Current treatments that use hematopoietic progenitor cell (HPC) transplantation in acute myeloid leukemia (AML) patients substantially reduce the risk of relapse, but are limited by the availability of immune compatible healthy HPCs. Although cellular reprogramming has the potential to provide a novel autologous source of HPCs for transplantation, the applicability of this technology toward the derivation of healthy autologous hematopoietic cells devoid of patient-specific leukemic aberrations from AML patients must first be evaluated...
June 2015: Stem Cells
Brendan A S McIntyre, Cantas Alev, Rami Mechael, Kyle R Salci, Jung Bok Lee, Aline Fiebig-Comyn, Borhane Guezguez, Yuping Wu, Guojun Sheng, Mickie Bhatia
Production of human embryonic stem cell (hESC)-derived lung progenitors has broad applicability for drug screening and cell therapy; however, this is complicated by limitations in demarcating phenotypic changes with functional validation of airway cell types. In this paper, we reveal the potential of hESCs to produce multipotent lung progenitors using a combined growth factor and physical culture approach, guided by the use of novel markers LIFRα and NRP1. Lung specification of hESCs was achieved by priming differentiation via matrix-specific support, followed by air-liquid interface to allow generation of lung progenitors capable of in vitro maturation into airway epithelial cell types, resulting in functional characteristics such as secretion of pulmonary surfactant, ciliation, polarization, and acquisition of innate immune activity...
January 2014: Stem Cells Translational Medicine
Allison L Boyd, Kyle R Salci, Zoya Shapovalova, Brendan A S McIntyre, Mickie Bhatia
Recent work has shown that leukemic stem cell self-renewal in chronic myeloid leukemia is dependent on cell-intrinsic hedgehog (Hh) signaling, and early clinical trials suggest that targeting this pathway is also therapeutic in patients with acute myeloid leukemia (AML). In this study, we aimed to better understand Hh signaling in normal hematopoiesis and AML by molecularly and functionally analyzing more than 200 primary human AML patient samples compared with nonleukemic controls. Gene expression analysis indicated that Hh pathway transcripts were similarly regulated in AML and nonleukemic controls, regardless of whether samples were purified based on primitive phenotypes...
October 2013: Experimental Hematology
Kyle R Salci, Brendan A S McIntyre, Mickie Bhatia
Direct conversion of cellular fate provides a potential approach to generate cells of the hematopoietic lineage without the requisite reversion to a pluripotent state via somatic cell reprogramming. The utilization of this technology has enabled transcription factor-mediated conversion of somatic cell types to primitive and mature hematopoietic cells. Recent studies demonstrate that the direct conversion of somatic cells to the hematopoietic lineage likely requires the use of pioneer transcription factors to establish an accessible chromatin state that is responsive to enforced expression of hematopoietic-specific transcription factors, in combination with appropriate culture conditions that facilitate reprogramming...
October 2013: Current Opinion in Genetics & Development
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