Monti Lab

Mission Statement

Our laboratory integrates systems biology, machine learning, and bioinformatics approaches to investigate the molecular drivers of human disease, with the goals of advancing prevention and care. This multidisciplinary effort relies on the development of novel computational methodologies, and on the design of experiments based on the generation and integrative analysis of high-throughput multi-omics data, with the goal of identifying novel therapeutic targets and developing accurate diagnostic and prognostic biomarkers. Specific areas of research include the study of the molecular mechanisms of tumor initiation and progression and of the role played in it by environmental exposure, as well as the study of the biological factors contributing to healthy aging and extreme longevity.

Background

Stefano Monti is a Computational Biologist and joined the BU faculty as an associate professor in January 2011 in the section of Computational Biomedicine, with a joint appointment in the Bioinformatics program. Monti received his Ph.D. in Intelligent Systems and Artificial Intelligence from the University of Pittsburgh, and completed his training with a post-doctoral fellowship at the Robotics Institute at Carnegie Mellon. His doctoral and post-doctoral research focused on the development of machine learning and knowledge discovery methodologies, with a particular emphasis on probabilistic reasoning and Bayesian approaches to modeling biomedical data. Since 2001, he has worked in the field of Cancer Genomics, first as a Research Scientist at the Whitehead Institute’s Center for Genome Research, and later as a Computational Biologist in the Cancer Program at the Broad Institute.

Ongoing Projects

Principal Investigator
Stefano Monti

Graduate Students
Andrew Chen
Ziwei Huang
Lina Kroehling*
Mohammed Muzamil Khan
Anastasia Leshchyk
Vanessa Mengze Li
Amulya Shastry

          *Lina Kroehling recently awarded for a NIH F31 Pre-Doctoral Fellowship

Bioinformaticians
Reina Chau

Past Trainees

Anthony Federico
Daniel Gusenleitner
Anastasia Gurinovich
Tanya Karagiannis
Vinay Kartha
Stephanie Kim
Amy Li
Francesca Mulas
Eric Reed
Yuxiang Tan
Liye Zhang

Collaborators (outside of BU medical center)
Andrew Emili, Ph.D., OHSU Knight Cancer Institute, School of Medicine
Nicholas Schork, Ph.D., Quantitative Medicine & Systems Biology Division, Translational Genomics Research Institute (TGen).
Noa Rappaport, Ph.D., Institute for Systems Biology (ISB)
Senthil K Muthuswamy, PhD, Beth Israel Deaconess Medical Center, Boston, MA
Margaret Shipp, M.D, Dana Farber Cancer Institute, Boston, MA
Todd R. Golub, M.D., Broad Institute, Cambridge, MA
Nika Danial, Ph.D., Dana Farber Cancer Institute, Boston, MA
Scott J. Rodig, M.D. Ph.D., Brigham & Women’s Hospital, Boston, MA
Roberto Chiarle, M.D., Children Hospital, Boston, MA
Scott Auerbach, Ph.D., National Toxicology Program/NIEHS

Recent Publications

[complete and up-to-date list]

    1. Khan MM, Frustino J, Villa A, Nguyen B, Woo S, Johnson WE, Varelas X;, Kukuruzinska MA;, Monti S; (2023). Total RNA sequencing reveals gene expression and microbial alterations shared by oral pre‑malignant lesions and cancer. Human Genomics 17:72. PMID: 36993637.
    2. Reed ER, Jankowski SA, Spinella AJ, Noonan V, Haddad R, Nomoto K, Matsui J, Bais MV, Varelas X;, Kukuruzinska MA;, Monti S; (2023). β-catenin/CBP activation of mTORC1 signaling promotes partial epithelial-mesenchymal states in head and neck cancer. Translational Research (In press). PMID: 37353110.
    3. Karagiannis TT, Monti S, Sebastiani P (2023). Bayesian Differential Analysis of Cell Type Proportions. Frontiers in Genetics (In press). PMID: 37323674
    4. Federico A, Kern J, Varelas X, and Monti S (2023). Structure Learning for Hierarchical Regulatory Networks. PLoS Comp. Bio. 19(5): e1011118. PMID: 37200395
    5. Karagiannis T*, Dowrey TW*, Villacorta-Martin C, Montano M, Reed E, Andersen SL, Perls TT, Monti S, Murphy GJ, Sebastiani P (2023). Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity. Lancet eBiomedicine 90:104514. PMID: 37005201. PMCID: PMC10114155.
    6. Kern J, Tilston-Lunel A, Federico A, Ning B, Mueller A, Peppler G, Stampouloglou E, Cheng N, Johnson, R, Lenburg M, Beane J, Monti S, Varelas X (2022). Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas. Nature Communications 13(1):7198. PMID: 36443313. PMCID: PMC9705439.
    7. Karagiannis T, Monti S, Sebastiani P (2022). Cell Type Diversity Statistic: An entropy-based metric to compare overall cell type composition across samples. Frontiers in Genetics 13:855076. PMID: 35464841.
    8. Federico A, Monti S (2021). Contextualized Protein-Protein Interactions. Patterns (NY), 2(1):100153. PMID: 33511361. PMCID: PMC7815950.
    9. Kim S*, Reed ER*, Monti S, Schlezinger JJ (2021). A Data-Driven Transcriptional Taxonomy of Adipogenic Chemicals to Identify White and Brite Adipogens. Environmental Health Perspectives 129(7):077006. PMID: 34323617.
    10. Reed ER, Monti S (2021). Multi-Resolution Characterization of Molecular Taxonomies in Bulk and Single-Cell Transcriptomics Data. Nucleic Acids Research, 49(17):e98. PMID: 34226941.
    11. Federico A, Monti S (2020). hypeR: An R Package for Geneset Enrichment Workflows. Bioinformatics 36(4):1307. PMID: 31498385.
    12. Li A, Chapuy B, Varelas X, Sebastiani P, Monti S (2019). Identification of candidate cancer drivers by integrative Epi-DNA and Gene Expression (iEDGE) data analysis. Scientific Reports 9(1):16904. PMID: 31729402.
    13. Kartha VK, Sebastiani P, Kern J, Zang L, Varelas X, Monti S (2019). CaDrA: A computational framework for performing candidate driver analyses using genomic features. Frontiers in Genetics 10:121. PMID: 30838036. PMCID: PMC6390206.
    14. Li AJ, Lu X, Natoli T, Bittker J, Sipes N, Subramanian A, Auerbach S, Sherr DH, Monti S (2019). The Carcinogenome Project: High-Throughput In-vitro Gene Expression Profiling of Chemical Perturbations to Predict Long-Term Carcinogenicity. Environmental Health Perspectives 127(4):47002. PMCID:  PMC6785232. PMID: 30964323.
    15. Kartha VK*, Stawski L*, Han R, Haines P, Gallagher G, Noonan V, Kukuruzinska M, Monti S, Trojanowska T (2016). PDGFRβ is a novel marker of stromal activation in oral squamous cell carcinomas. PLoS One 11(4): e0154645. PMCID: PMC4851360.
    16. Zhang L, Yang CS, Varelas X, Monti S (2016). Altered RNA editing in 3’ UTR perturbs microRNA-mediated regulation of oncogenes and tumor-suppressors. Nature Scientific Reports 6:23226. PMCID: PMC4793219.
    17. Chapuy B, Roemer MGM, Stewart C, Tan Y, Abo R, Zhang L, Dunford AJ, Meredith D, Thorner A, Jordanova ES, Liu G, Feuerhake F, Ducar M, Illerhaus G, Gusenleitner D, Linden E, Sun HH, Homer H, Aono M, Pinkus G, Ligon A, Ligon K, Ferry J, Freeman GJ, van Hummelen P, Golub TR, Getz G, Rodig SJ, de Jong D, Monti S, Shipp MA (2015). Targetable Genetic Features of Primary Testicular and Primary Central Nervous System Lymphomas. Blood 127(7):869-881. PMCID: PMC4760091.
    18. Hiemer SE, Zhang L, Kartha VK, Packer TS, Almershed M, Noonan V, Kukuruzinska M, Bais MV, Monti S, Varelas X (2015). A YAP/TAZ-Regulated Molecular Signature is Associated with Oral Squamous Cell Carcinoma. Molecular Cancer Research 13(6):957-68. PMCID: PMC4470857.
    19. Carey C, Gusenleitner D, Chapuy B, Kovach AE, Kluk MJ, Sun HH, Crossland RE, Bacon CM, Rand V, Dal Cin P, Le LP, Neuberg D, Sohani AR, Monti S, Rodig S (2015). Molecular Classification of MYC-Driven B-cell Lymphomas by Targeted Gene Expression Profiling of Fixed Biopsy Specimens. Journal of Molecular Diagnostics 17(1):19-30. PMCID: PMC4279427.
    20. Gusenleitner D, Auerbach S, Meila T, Gómez H, Sherr DH, Monti S (2014). Genomic models of short-term exposure accurately predict long-term chemical carcinogenicity and identify putative mechanisms of action. PLoS ONE 9(7):e102579 [Chemical watch review; Voice of America report]
    21. Chapuy B, McKeown MR, Lin C, Monti S, Roemer MGM, Qi J, Rahl P, Sun H, Yeda KT, Kung AJ, Rodig SJ, Young RA, Shipp MA, and Bradner JE (2013). Disruption of Super Enhancer Driven Cancer Dependencies in Diffuse Large B-Cell Lymphoma. Cancer Cell 24(6):777-790. PMCID: PMC4018722
    22. Chen L, Monti S, Juszczynski P, Ouyang J, Chapuy B, Neuberg D, Doench JG, et al. (2013). SYK Inhibition Modulates Distinct PI3K/AKT- Dependent Survival Pathways and Cholesterol Biosynthesis in Diffuse Large B Cell Lymphomas. Cancer Cell, 23(6), 826–838. [Cancer Discovery review]
    23. Hartley SW, Monti S, Liu CT, Steinberg MH, and Sebastiani P (2012) Bayesian methods for multivariate modeling of pleiotropic SNP associations and genetic risk prediction, Frontiers in Genetics, 3:176
    24. Caro P, Kishan  AU, Norberg E, Stanley I, Chapuy B, Ficarro SB, Polak K, Tondera D, Gounarides J, Yin H, Zhou F, Green MR, Chen L, Monti S, Marto JA, Shipp MA, Danial N. Metabolic Signatures Uncover Novel Targets in Molecular Subsets of Diffuse Large B Cell Lymphoma. Cancer Cell, 22(4) 547-560. 2012. [Cancer Cell review]
    25. Monti S, Chapuy B, Takeyama K, Rodig SJ, Hao Y, T. Yeda KT, Inguilizian H, Mermel C, Curie T, Dogan A, Kutok JL, Beroukim R, Neuberg D, Habermann T, Getz G, Kung AL, Golub TR, Shipp MA. Integrative Analysis Reveals an Outcome-associated and Targetable Pattern of p53 and Cell Cycle Deregulation in Diffuse Large B-cell Lymphoma, Cancer Cell, 22(3):359-372, 2012.
    26. Chiarle R, Zhang Y, Frock RL, Lewis SM, Molinie B, Ho Y, Myers DR,  Choi VW, Compagno M, Malkin DJ, Neuberg D, Monti S, Giallourakis CC, Gostissa M,  and Alt FW. Genome-Wide Translocation Sequencing Reveals Mechanisms of Chromosome Breaks and Rearrangements in B Cells. Cell, 147:(1):107-119, 2011.
    27. Green M, Monti S, et al., Signatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program. PNAS, 108(7): 2873-2878, 2011.
    28. Chapman M, et al. Initial genome sequencing and analysis of multiple myeloma. Nature, 471(7339):467–472, 2011.
    29. Green M, Monti S, et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular Sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood, 116(17): 3268-3277, 2010.
    30. The Cancer Genome Atlas (TCGA) Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature, 455(7216):1061-8, 2008.
    31. Takeyama K, Monti S, et al., Integrative Analysis Reveals 53BP1 Copy Loss and Decreased Expression in a Subset of Human Diffuse Large B-cell Lymphomas. Oncogene, 27(3): 318-322, 2008.
    32. Polo JM, Juszczynski P, Monti S, et al. A transcriptional signature with differential expression of BCL6 target genes accurately identifies BCL6-dependent diffuse large B-cell lymphomas. PNAS, 104(9): 3207-3212, 2007.
    33. Hayes DN, Monti S, et al., Gene Expression Profiling Reveals Reproducible Human Lung Adenocarcinoma Subtypes in Multiple Independent DNA Microarray Cohorts. J Clinical Oncology, 24(31): 5079-5090, 2006.
    34. Monti, S., Savage, K.J., et al., Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response. Blood, 2005. 105(5): p. 1851-1861.
    35. Monti, S., et al., Consensus Clustering: A Resampling-Based Method for Class Discovery and Visualization of Gene Expression Microarray Data. Machine Learning, 2003. 52(1-2): p. 91-118.