Shanshan Pei

Zhejiang University

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Craig T. Jordan

University of Colorado Anschutz Medical Campus

105

Brett M. Stevens

University of Colorado Anschutz Medical Campus

Daniel A. Pollyea

University of Colorado Denver

Mohammad Minhajuddin

University of Colorado Denver

Clayton A. Smith

University of Colorado Anschutz Medical Campus

Maria L. Amaya

University of Colorado System

Anagha Inguva

University of Colorado Anschutz Medical Campus

Amanda Winters

University of Colorado Denver

Austin E. Gillen

University of Colorado Anschutz Medical Campus

Jeffrey Schowinsky

University of Colorado Anschutz Medical Campus

Cooperative Institutions

University of Colorado Denver

107

University of Colorado Anschutz Medical Campus

100

Zhejiang University

First Affiliated Hospital Zhejiang University

Zhejiang Chinese Medical University

University of Rochester Medical Center

Southern Medical University

University of Colorado Cancer Center

University of Rochester

Cell Technology (China)

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Elevated soluble syndecan-1 levels in neuromyelitis optica are associated with disease severity

Cytokine (2018)

Shanshan Pei Zheng Dong Zhanhang Wang Xueqiang Hu Suyue Pan

Neuromyelitis Optica

10.1016/j.cyto.2018.08.017

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Citations (17)

Monocytic Subclones Confer Resistance to Venetoclax-Based Therapy in Patients with Acute Myeloid Leukemia

Cancer Discovery (2020)

Shanshan Pei Daniel A. Pollyea Annika Gustafson Brett M. Stevens Mohammad Minhajuddin

Venetoclax-based therapy can induce responses in approximately 70% of older previously untreated patients with acute myeloid leukemia (AML). However, up-front resistance as well as relapse following initial response demonstrates the need for a deeper understanding of resistance mechanisms. In the present study, we report that responses to venetoclax +azacitidine in patients with AML correlate closely with developmental stage, where phenotypically primitive AML is sensitive, but monocytic AML is more resistant. Mechanistically, resistant monocytic AML has a distinct transcriptomic profile, loses expression of venetoclax target BCL2, and relies on MCL1 to mediate oxidative phosphorylation and survival. This differential sensitivity drives a selective process in patients which favors the outgrowth of monocytic subpopulations at relapse. Based on these findings, we conclude that resistance to venetoclax + azacitidine can arise due to biological properties intrinsic to monocytic differentiation. We propose that optimal AML therapies should be designed so as to independently target AML subclones that may arise at differing stages of pathogenesis. SIGNIFICANCE: Identifying characteristics of patients who respond poorly to venetoclax-based therapy and devising alternative therapeutic strategies for such patients are important topics in AML. We show that venetoclax resistance can arise due to intrinsic molecular/metabolic properties of monocytic AML cells and that such properties can potentially be targeted with alternative strategies.

Venetoclax

Azacitidine

Monocytic leukemia

10.1158/2159-8290.cd-19-0710

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Citations (361)

Targeting Acute Myeloid Leukemia Stem Cells through Perturbation of Mitochondrial Calcium

Cancer Discovery (2024)

Anagha Inguva Mark J. Althoff Hunter Tolison Krysta L. Engel Maria L. Amaya

Acute myeloid leukemia stem cells (LSCs) are uniquely reliant on oxidative phosphorylation (OXPHOS) for survival. Moreover, maintenance of OXPHOS is dependent on BCL-2, creating a therapeutic opportunity to target LSCs using the BCL-2 inhibitor venetoclax. Although venetoclax-based regimens have shown promising clinical activity, the emergence of drug resistance is prevalent. Thus, in the present study, we investigated how mitochondrial properties may influence venetoclax responsiveness. Our data show that utilization of mitochondrial calcium is fundamentally different between drug-responsive and nonresponsive LSCs. By comparison, venetoclax-resistant LSCs demonstrate an active metabolic (i.e., OXPHOS) status with relatively high levels of calcium. Consequently, we tested genetic and pharmacological approaches to target the mitochondrial calcium uniporter. We demonstrate that inhibition of calcium uptake reduces OXPHOS and leads to eradication of venetoclax-resistant LSCs. These findings demonstrate a central role for calcium signaling in LSCs and provide an avenue for clinical management of venetoclax resistance. Significance: We identify increased utilization of mitochondrial calcium as a distinct metabolic requirement of venetoclax-resistant LSCs and demonstrate the potential of targeting mitochondrial calcium uptake as a therapeutic strategy.

Venetoclax

10.1158/2159-8290.cd-23-1145

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Citations (4)

Interleukin-1 receptor associated kinase (IRAK)-M -mediated type 2 microglia polarization ameliorates the severity of experimental autoimmune encephalomyelitis (EAE)

Journal of Autoimmunity (2019)

Liu Baozhu Yong Gu Shanshan Pei Peng Yu Jinyu Chen

Pathogenesis

10.1016/j.jaut.2019.04.020

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Citations (46)

Supplementary Tables S1-S6 from Monocytic Subclones Confer Resistance to Venetoclax-Based Therapy in Patients with Acute Myeloid Leukemia

Shanshan Pei Daniel A. Pollyea Annika Gustafson Brett M. Stevens Mohammad Minhajuddin

Supplementary Tables S1-S6 describing patient characteristics, gene lists, LSC signatures, and reagents.

Venetoclax

Monocytic leukemia

THP1 cell line

10.1158/2159-8290.22535507

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Citations (0)

Supplementary Figures S1-S7 from A novel type of monocytic leukemia stem cell revealed by the clinical use of venetoclax-based therapy

Shanshan Pei Ian T. Shelton Austin E. Gillen Brett M. Stevens Maura Gasparetto

Supplementary Fig. 1: Immunophenotyping and WES analysis of primary AML specimens. Supplementary Fig. 2: Immunophenotyping of engrafted cells in PDX. Supplementary Fig. 3: WES analysis and remission duration of VEN/AZA relapsed AML patients. Supplementary Fig. 4: CITE-seq data analysis. Supplementary Fig. 5: Sorting strategies for determining m-LSC immunophenotype and expression of various LSC markers in m-LSCs. Supplementary Fig. 6: Molecular properties and targeting of m-LSCs in vitro and in vivo. Supplementary Fig. 7: M5 but not M4 patients showing significantly higher refractory rate to VEN/AZA therapy.

Venetoclax

Monocytic leukemia

10.1158/2159-8290.27025877

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Citations (0)

Single-Cell Transcriptional Survey of Murine Intestinal Graft-Versus-Host Disease

Fei Gao Hengwei Wu Xin Jin Zhuoyue Shi Limengmeng Wang

10.2139/ssrn.4804115

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Supplementary Tables 3-5 from A Novel Type of Monocytic Leukemia Stem Cell Revealed by the Clinical Use of Venetoclax-Based Therapy

Shanshan Pei Ian T. Shelton Austin E. Gillen Brett M. Stevens Maura Gasparetto

List of commonly mutated genes in AML, Clinical information of VEN/AZA relapsed AML patients, CITE-seq and flow antibodies

Venetoclax

Monocytic leukemia

10.1158/2159-8290.24091939

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Citations (0)

Shedding of Glycocalyx Components in Neuromyelitis Optica: Initial Predictor of Immune Attack?

Research Square (Research Square) (2021)

Qi Zhang Shanshan Pei Jinyu Chen Yu Peng Zheyi Zhou

Abstract Background: Neuromyelitis optica (NMO), multiple sclerosis (MS) and autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy are idiopathic inflammatory demyelinating diseases (IIDDs) that mainly present as encephalomyelitis. Heparan sulfate (HS) and hyaluronic acid (HA) are two components of glycocalyx, a carbohydrate-rich layer on the surface of blood vessels that mediates interaction with blood. Degradation of glycocalyx in IIDDs is poorly understood. Purpose: To detect the serum and cerebrospinal fluid (CSF) levels of shed HS and HA and to correlate these levels with disease severity to determine their diagnostic value. Methods: We obtained serum and CSF samples from 24 NMO patients, 15 MS patients, 10 autoimmune GFAP astrocytopathy patients, and 18 controls without non-inflammatory neurological diseases. Soluble HS and HA, and IFNγ, IL17A, and matrix metalloproteinase (MMP) 1 were detected via ELISA. Results: Serum and CSF levels of HS, HA and related cytokines but not of plasma MMP1 were significantly elevated in these diseases. Notably, HS and HA levels were positively correlated with Expanded Disability Status Scale scores. Conclusions: Our results indicate glycocalyx degradation and inflammation in NMO, MS and autoimmune GFAP astrocytopathy. Moreover, increased shedding of HS or HA may indicate a worse clinical situation. Furthermore, therapeutic strategies that protect glycocalyx may be effective in these diseases.

Glycocalyx

Neuromyelitis Optica

10.21203/rs.3.rs-442607/v1

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Research on Interface Design Strategies of Online Course Video Based on Cognitive Load

2020 International Conference on Innovation Design and Digital Technology (ICIDDT) (2020)

Shanshan Pei Liqing Huang Mingzhu Li

With the deepening of digital education and information technology, the gradual rise of distance education and Massive Open Online Courses has further promoted the sharing of teaching resources and the fairness of education, However, due to the lack of design strategy guidance, Many online course video interface design is unreasonable, which increases the cognitive load of learners, affects the learning efficiency of learners, and then leads to a high dropout rate. Based on cognitive load theory, this paper analyzes the current situation of online course video interface design in Open Education in our country by using literature analysis and questionnaire survey; Through case study, the design elements of online course video interface are sorted out, and the design elements related to cognitive load are selected from three aspects: intrinsic cognitive load, extrinsic cognitive load and effective cognitive load; In the end, This paper puts forward the design strategy of online course video interface based on cognitive load, and creates the design template of online course video interface, which can be flexibly applied in the design of online course video interface, and proposes solutions to improve the quality of online course from the perspective of design.

Cognitive Load

Interface (matter)

Course (navigation)

Interface design

10.1109/iciddt52279.2020.00039

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Citations (1)