I am a joint postdoctoral scholar in the labs of Drs. Ash Alizadeh and Aaron Newman. My interest lies in better understanding the cellular heterogeneity of tumors.
Honors & Awards
2019 AACR-AstraZeneca Lymphoma Research Fellowship, American Association for Cancer Research (2019.07.01-2021.06.30)
Abstract Achievement Award, American Society of Hematology (2017)
Travel Grant, Norwegian Research School in Bioinformatics, Biostatistics and System Biology (2017.09.01-2018.02.28)
McKinsey & Company Oslo Scholarship, McKinsey & Company (2013)
Research Stipend, S. G. Sønneland Foundation (2011)
Boards, Advisory Committees, Professional Organizations
Associate member, American Association for Cancer Research (2019 - Present)
Member, International Society for Computational Biology (2018 - Present)
Member, Norwegian Research School in Bioinformatics, Biostatistics and Systems Biology (2015 - 2018)
Ph.D., Department of Informatics, University of Oslo, Norway, Computational Biology (2018)
M.Sc, Department of Biosciences, University of Oslo, Norway., Molecular Biosciences, Cancer Biology (2013)
B.Sc, Department of Biosciences, University of Oslo, Norway, Molecular Biology (2010)
Determining cell type abundance and expression from bulk tissues with digital cytometry.
Single-cell RNA-sequencing has emerged as a powerful technique for characterizing cellular heterogeneity, but it is currently impractical on large sample cohorts and cannot be applied to fixed specimens collected as part of routine clinical care. We previously developed an approach for digital cytometry, called CIBERSORT, that enables estimation of cell type abundances from bulk tissue transcriptomes. We now introduce CIBERSORTx, a machine learning method that extends this framework to infer cell-type-specific gene expression profiles without physical cell isolation. By minimizing platform-specific variation, CIBERSORTx also allows the use of single-cell RNA-sequencing data for large-scale tissue dissection. We evaluated the utility of CIBERSORTx in multiple tumor types, including melanoma, where single-cell reference profiles were used to dissect bulk clinical specimens, revealing cell-type-specific phenotypic states linked to distinct driver mutations and response to immune checkpoint blockade. We anticipate that digital cytometry will augment single-cell profiling efforts, enabling cost-effective, high-throughput tissue characterization without the need for antibodies, disaggregation or viable cells.
View details for PubMedID 31061481
- A clinico-molecular predictor identifies follicular lymphoma patients at risk of early transformation after first-line immunotherapy. Haematologica 2019
Computational approaches for characterizing the tumor immune microenvironment.
Recent advances in high-throughput molecular profiling technologies and multiplexed imaging platforms have revolutionized our ability to characterize the tumor immune microenvironment. As a result, studies of tumor-associated immune cells increasingly involve complex datasets that require sophisticated methods of computational analysis. In this review, we present an overview of key assays and related bioinformatics tools for analyzing the tumor-associated immune system in bulk tissues and at the single-cell level. In parallel, we describe how data science strategies and novel technologies have advanced tumor immunology and opened the door for new opportunities to exploit host immunity to improve cancer clinical outcomes. This article is protected by copyright. All rights reserved.
View details for DOI 10.1111/imm.13101
View details for PubMedID 31347163
Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable Effect With Low Toxicity: Results From Two Nordic Lymphoma Group Trials With More Than 10 Years of Follow-Up
JOURNAL OF CLINICAL ONCOLOGY
2018; 36 (33): 3315-+
For indolent lymphoma, the optimal timing, sequence, and choice of therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group randomized trials, symptomatic or clearly progressing patients were treated first line with a rituximab-containing regimen without chemotherapy. The purpose of this study was to assess long-term survival, risk of transformation, and need of new therapies.Data were collected at cross-sectional follow-up for 321 patients with indolent lymphoma (84% with follicular lymphomas [FL]) included in one of two Nordic Lymphoma Group trials (accrual 1998 to 1999 and 2002 to 2008). All patients received first-line therapy with one or two cycles of four weekly infusions of rituximab 375 mg/m2, and 148 were randomly allocated to the addition of interferon alfa-2a. Follow-up data were retrieved from initial trial databases and medical records on repeated clinical evaluations.At the end of follow-up, 73% of patients were alive, with a median follow-up after random assignment of 10.6 years. Among all, 36% (38% with FL) had never needed chemotherapy. For patients with FL who required new therapy within 24 months because of early disease progression, the 10-year survival rate was 59% versus 81% for those with longer remission. Interferon was not shown to improve long-term outcome. Transformation was diagnosed in 20% of all patients (2.4% per person-year) and in 18% with FL. An additional malignancy was found in 12%.Approximately one third of patients with symptomatic indolent lymphoma (30% with FL, 23% without FL) did not need new therapy in the long term after first-line rituximab without chemotherapy. In the entire cohort, 10-year survival was excellent with no major safety issues, which suggests that chemotherapy can be delayed safely in the majority of patients.
View details for DOI 10.1200/JCO.18.00262
View details for Web of Science ID 000451965300006
View details for PubMedID 30285560
Artesunate shows potent anti-tumor activity in B-cell lymphoma
JOURNAL OF HEMATOLOGY & ONCOLOGY
2018; 11: 23
Although chemo-immunotherapy has led to an improved overall survival for most B-cell lymphoma types, relapsed and refractory disease remains a challenge. The malaria drug artesunate has previously been identified as a growth suppressor in some cancer types and was tested as a new treatment option in B-cell lymphoma.We included artesunate in a cancer sensitivity drug screen in B lymphoma cell lines. The preclinical properties of artesunate was tested as single agent in vitro in 18 B-cell lymphoma cell lines representing different histologies and in vivo in an aggressive B-cell lymphoma xenograft model, using NSG mice. Artesunate-treated B lymphoma cell lines were analyzed by functional assays, gene expression profiling, and protein expression to identify the mechanism of action.Drug screening identified artesunate as a highly potent anti-lymphoma drug. Artesunate induced potent growth suppression in most B lymphoma cells with an IC50 comparable to concentrations measured in serum from artesunate-treated malaria patients, while leaving normal B-cells unaffected. Artesunate markedly inhibited highly aggressive tumor growth in a xenograft model. Gene expression analysis identified endoplasmic reticulum (ER) stress and the unfolded protein response as the most affected pathways and artesunate-induced expression of the ER stress markers ATF-4 and DDIT3 was specifically upregulated in malignant B-cells, but not in normal B-cells. In addition, artesunate significantly suppressed the overall cell metabolism, affecting both respiration and glycolysis.Artesunate demonstrated potent apoptosis-inducing effects across a broad range of B-cell lymphoma cell lines in vitro, and a prominent anti-lymphoma activity in vivo, suggesting it to be a relevant drug for treatment of B-cell lymphoma.
View details for DOI 10.1186/s13045-018-0561-0
View details for Web of Science ID 000425552600001
View details for PubMedID 29458389
View details for PubMedCentralID PMC5819282
T Cells Expressing Checkpoint Receptor TIGIT Are Enriched in Follicular Lymphoma Tumors and Characterized by Reversible Suppression of T-cell Receptor Signaling
CLINICAL CANCER RESEARCH
2018; 24 (4): 870–81
Purpose: T cells infiltrating follicular lymphoma (FL) tumors are considered dysfunctional, yet the optimal target for immune checkpoint blockade is unknown. Characterizing coinhibitory receptor expression patterns and signaling responses in FL T-cell subsets might reveal new therapeutic targets.Experimental Design: Surface expression of 9 coinhibitory receptors governing T-cell function was characterized in T-cell subsets from FL lymph node tumors and from healthy donor tonsils and peripheral blood samples, using high-dimensional flow cytometry. The results were integrated with T-cell receptor (TCR)-induced signaling and cytokine production. Expression of T-cell immunoglobulin and ITIM domain (TIGIT) ligands was detected by immunohistochemistry.Results: TIGIT was a frequently expressed coinhibitory receptor in FL, expressed by the majority of CD8 T effector memory cells, which commonly coexpressed exhaustion markers such as PD-1 and CD244. CD8 FL T cells demonstrated highly reduced TCR-induced phosphorylation (p) of ERK and reduced production of IFNγ, while TCR proximal signaling (p-CD3ζ, p-SLP76) was not affected. The TIGIT ligands CD112 and CD155 were expressed by follicular dendritic cells in the tumor microenvironment. Dysfunctional TCR signaling correlated with TIGIT expression in FL CD8 T cells and could be fully restored upon in vitro culture. The costimulatory receptor CD226 was downregulated in TIGIT+ compared with TIGIT- CD8 FL T cells, further skewing the balance toward immunosuppression.Conclusions: TIGIT blockade is a relevant strategy for improved immunotherapy in FL. A deeper understanding of the interplay between coinhibitory receptors and key T-cell signaling events can further assist in engineering immunotherapeutic regimens to improve clinical outcomes of cancer patients. Clin Cancer Res; 24(4); 870-81. ©2017 AACR.
View details for DOI 10.1158/1078-0432.CCR-17-2337
View details for Web of Science ID 000425191300015
View details for PubMedID 29217528
View details for PubMedCentralID PMC5815910
Favorable lifestyle before diagnosis associated with lower risk of screen-detected advanced colorectal neoplasia
WORLD JOURNAL OF GASTROENTEROLOGY
2016; 22 (27): 6276–86
To investigate the association between adherence to health recommendations and detection of advanced colorectal neoplasia (ACN) in colorectal cancer (CRC) screening.A total of 14832 women and men were invited to CRC screening, 6959 in the fecal immunochemical test arm and 7873 in the flexible sigmoidoscopy arm. These were also sent a self-reported lifestyle questionnaire to be completed prior to their first CRC screening. A lifestyle score was created to reflect current adherence to healthy behaviors in regard to smoking, body mass index, physical activity, alcohol consumption and food consumption, and ranged from zero (poorest) to six (best). Odds ratios (ORs) and 95%CIs were calculated using multivariable logistic regression to evaluate the association between the single lifestyle variables and the lifestyle score and the probability of detecting ACN.In all 6315 women and men completed the lifestyle questionnaire, 3323 (53%) in the FIT arm and 2992 (47%) in the FS arm. This was 89% of those who participated in screening. ACN was diagnosed in 311 (5%) participants of which 25 (8%) were diagnosed with CRC. For individuals with a lifestyle score of two, three, four, and five-six, the ORs (95%CI) for the probability of ACN detection were 0.82 (0.45-1.16), 0.43 (0.28-0.73), 0.41 (0.23-0.64), and 0.41 (0.22-0.73), respectively compared to individuals with a lifestyle score of zero-one. Of the single lifestyle factors, adherence to non-smoking and moderate alcohol intake were associated with a decreased probability of ACN detection compared to being a smoker or having a high alcohol intake 0.53 (0.42-0.68) and 0.63 (0.43-0.93) respectively.Adopted healthy behaviors were inversely associated with the probability of ACN detection. Lifestyle assessment might be useful for risk stratification in CRC screening.
View details for DOI 10.3748/wjg.v22.i27.6276
View details for Web of Science ID 000380769700016
View details for PubMedID 27468217
View details for PubMedCentralID PMC4945986
ALIX and ESCRT-III Coordinately Control Cytokinetic Abscission during Germline Stem Cell Division In Vivo
2015; 11 (1): e1004904
Abscission is the final step of cytokinesis that involves the cleavage of the intercellular bridge connecting the two daughter cells. Recent studies have given novel insight into the spatiotemporal regulation and molecular mechanisms controlling abscission in cultured yeast and human cells. The mechanisms of abscission in living metazoan tissues are however not well understood. Here we show that ALIX and the ESCRT-III component Shrub are required for completion of abscission during Drosophila female germline stem cell (fGSC) division. Loss of ALIX or Shrub function in fGSCs leads to delayed abscission and the consequent formation of stem cysts in which chains of daughter cells remain interconnected to the fGSC via midbody rings and fusome. We demonstrate that ALIX and Shrub interact and that they co-localize at midbody rings and midbodies during cytokinetic abscission in fGSCs. Mechanistically, we show that the direct interaction between ALIX and Shrub is required to ensure cytokinesis completion with normal kinetics in fGSCs. We conclude that ALIX and ESCRT-III coordinately control abscission in Drosophila fGSCs and that their complex formation is required for accurate abscission timing in GSCs in vivo.
View details for DOI 10.1371/journal.pgen.1004904
View details for Web of Science ID 000349314600024
View details for PubMedID 25635693
View details for PubMedCentralID PMC4312039
Primary cold agglutinin-associated lymphoproliferative disease: a B-cell lymphoma of the bone marrow distinct from lymphoplasmacytic lymphoma
2014; 99 (3): 497–504
Primary chronic cold agglutinin disease is a rare hemolytic disease mediated by monoclonal IGHV4-34-encoded cold agglutinins with a predominant specificity for the blood group antigen I. Bone marrow from 54 patients was studied to type the underlying lymphoproliferative disorder better. Bone marrow biopsies showed circumscribed intra-parenchymatous nodules with small monotonous monoclonal B cells in 40/54 patients (median infiltration: 10% of marrow cells) with a CD20(+), IgMs(+), IgDs(+), CD27(+), CD5(-/+), CD11c(-), CD23(-), CD38(-) immunophenotype. Neither plasmacytoid cytological features nor expression of plasma cell differentiation-associated transcription factors MUM1, XBP1 and BLIMP1 were noted in these B cells. However, a limited number of mature monoclonal IgM(+), IgD(-) plasma cells were present outside the lymphoid nodules and were diffusely scattered throughout the marrow. Of interest, the MYD88 L265P mutation, typical of lymphoplasmacytic lymphoma, was not detected (17/17 cases). Somatically mutated monoclonal IGHV4-34 gene rearrangement was demonstrated in eight patients with frozen samples (mean sequence homology 95.4%). However, mutations of BCL6 intron 1 were not demonstrated, except in one patient, suggesting that the lymphoma cells had not matured in the germinal center. In conclusion, cold agglutinin-associated lymphoproliferative disease displays homogeneous histological and immunophenotypic features. The absence of plasmacytoid cells, the presence of plasma cells predominantly outside the nodular lymphoid infiltrates, IGHV4-34 restriction and absence of MYD88 L265P mutation strongly suggest that cold agglutinin-associated lymphoproliferative disease is a distinct entity that is different from lymphoplasmacytic lymphoma.
View details for DOI 10.3324/haematol.2013.091702
View details for Web of Science ID 000336255000020
View details for PubMedID 24143001
View details for PubMedCentralID PMC3943313