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Mohammad Fallahi-Sichani

Mohammad Fallahi-Sichani

Associate Professor, Biomedical Engineering, Biomedical Engineering

Primary Location
MR5 2215
Box 800759, Health System
Charlottesville, Virginia 22908
Primary Phone Number
434.924.9950
Email
[email protected]
Website
https://www.fallahi-sichani-lab.com/

Bio & Overview

The systems biology research in the Fallahi-Sichani lab is focused primarily on understanding the mechanisms through which human cancer cells respond heterogeneously to environmental and therapeutic perturbations. These responses can take the form of changes in gene expression, metabolic state, or cell fate decisions such as differentiation, cell division, growth arrest, or induction of cell death in response to cancer drugs. Interestingly, these responses vary among cells in different states, even those that are genetically identical. Understanding the mechanisms that underpin heterogeneous cell fate decisions and cellular plasticity has been a key challenge for quantitative biology and precision medicine. To address these challenges, we deploy cutting-edge, high-throughput, highly multiplexed technologies to generate hypothesis-driven datasets of single-cell behaviors, apply modern multivariate computational tools to analyze such high-dimensional datasets, and create quantitative models to describe tumor cell behaviors at single-cell, molecular and network levels. The iterative use of experimental and modeling methods enables us to discover novel mechanisms of cellular signaling, plasticity and heterogeneity in cancer cell state and drug response, validate these mechanisms, and utilize them to guide improvement in cancer therapies.

Academic Information

Department
Biomedical Engineering
Academic Title
Assistant Professor

Primary Education

  • PhD, Chemical Engineering, University of Michigan, 2012
  • Postdoc, Systems Biology, Harvard Medical School, 2017

Other Affiliations

  • Assistant Professor, Cancer Center
  • MSTP
  • BIMS

Research Interests

Cancer systems biology, Single-cell quantitative biology, Computational modeling

Research Disciplines

  • Biochemistry
  • Biomedical Engineering
  • Biotechnology
  • Cancer Biology
  • Cell and Developmental Biology
  • Computational Biology
  • Epigenetics
  • Experimental Pathology
  • Metabolism
  • Molecular Biology
  • Molecular Pharmacology
  • Molecular Physiology and Biological Physics
  • Translational Science

Research Opportunities

  • Biochemistry
  • Cancer Biology
  • Computational Biology
  • Experimental Pathology
  • Molecular Biology

PhD Programs

  • Biochemistry & Molecular Genetics

Selected Publications

2024

Hsu, J., Nguyen, K. T., Bujnowska, M., Janes, K. A., & Fallahi-Sichani, M. (2024). Protocol for iterative indirect immunofluorescence imaging in cultured cells, tissue sections, and metaphase chromosome spreads. STAR PROTOCOLS, 5(3). doi:10.1016/j.xpro.2024.103190

Abecunas, C., Kidd, A. D., Jiang, Y., Zong, H., & Fallahi-Sichani, M. (2024). Multivariate analysis of metabolic state vulnerabilities across diverse cancer contexts reveals synthetically lethal associations.. bioRxiv. doi:10.1101/2023.11.28.569098

2022

Abecunas, C., Whitehead, C. E., Ziemke, E. K., Baumann, D. G., Frankowski-McGregor, C. L., Sebolt-Leopold, J. S., & Fallahi-Sichani, M. (2023). Loss of NF1 in Melanoma Confers Sensitivity to SYK Kinase Inhibition. CANCER RESEARCH, 83(2), 316-331. doi:10.1158/0008-5472.CAN-22-0883

Comandante-Lou, N., Baumann, D. G., & Fallahi-Sichani, M. (2022). AP-1 transcription factor network explains diverse patterns of cellular plasticity in melanoma cells. CELL REPORTS, 40(5). doi:10.1016/j.celrep.2022.111147

2021

Khaliq, M., Manikkam, M., Martinez, E. D., & Fallahi-Sichani, M. (2021). Epigenetic modulation reveals differentiation state specificity of oncogene addiction. NATURE COMMUNICATIONS, 12(1). doi:10.1038/s41467-021-21784-2

2020

Shcherbina, A., Larouche, J., Fraczek, P., Yang, B. A., Brown, L. A., Markworth, J. F., . . . Aguilar, C. A. (2020). Dissecting Murine Muscle Stem Cell Aging through Regeneration Using Integrative Genomic Analysis. CELL REPORTS, 32(4). doi:10.1016/j.celrep.2020.107964

Comandante-Lou, N., Khaliq, M., Venkat, D., Manikkam, M., & Fallahi-Sichani, M. (2020). Phenotype-based probabilistic analysis of heterogeneous responses to cancer drugs and their combination efficacy. PLOS COMPUTATIONAL BIOLOGY, 16(2). doi:10.1371/journal.pcbi.1007688

2019

Khaliq, M., & Fallahi-Sichani, M. (2019). Epigenetic Mechanisms of Escape from BRAF Oncogene Dependency. CANCERS, 11(10). doi:10.3390/cancers11101480

2017

Keenan, A. B., Jenkins, S. L., Jagodnik, K. M., Koplev, S., He, E., Torre, D., . . . Pillai, A. (2018). The Library of Integrated Network-Based Cellular Signatures NIH Program: System-Level Cataloging of Human Cells Response to Perturbations. CELL SYSTEMS, 6(1), 13-24. doi:10.1016/j.cels.2017.11.001

Fallahi-Sichani, M., Becker, V., Izar, B., Baker, G. J., Lin, J. -R., Boswell, S. A., . . . Sorger, P. K. (2017). Adaptive resistance of melanoma cells to RAF inhibition via reversible induction of a slowly dividing de-differentiated state. MOLECULAR SYSTEMS BIOLOGY, 13(1). doi:10.15252/msb.20166796

2016

Lin, J. -R., Fallahi-Sichani, M., Chen, J. -Y., & Sorger, P. K. (2016). Cyclic Immunofluorescence (CycIF), A Highly Multiplexed Method for Single-cell Imaging.. Current protocols in chemical biology, 8(4), 251-264. doi:10.1002/cpch.14

Moerke, N., & Fallahi-Sichani, M. (2016). Reverse Phase Protein Arrays for Compound Profiling.. Current protocols in chemical biology, 8(3), 179-196. doi:10.1002/cpch.9

Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H. I. I., Treacy, D., Trombetta, J. J., . . . Garraway, L. A. (2016). Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. SCIENCE, 352(6282), 189-196. doi:10.1126/science.aad0501

2015

Lin, J. -R., Fallahi-Sichani, M., & Sorger, P. K. (2015). Highly multiplexed imaging of single cells using a high-throughput cyclic immunofluorescence method. NATURE COMMUNICATIONS, 6. doi:10.1038/ncomms9390

Fallahi-Sichani, M., Moerke, N. J., Niepel, M., Zhang, T., Gray, N. S., & Sorger, P. K. (2015). Systematic analysis of BRAFV600E melanomas reveals a role for JNK/c-Jun pathway in adaptive resistance to drug-induced apoptosis. MOLECULAR SYSTEMS BIOLOGY, 11(3). doi:10.15252/msb.20145877

2014

Kirschner, D. E., Hunt, C. A., Marino, S., Fallahi-Sichani, M., & Linderman, J. J. (2014). Tuneable resolution as a systems biology approach for multi-scale, multi-compartment computational models. WILEY INTERDISCIPLINARY REVIEWS-SYSTEMS BIOLOGY AND MEDICINE, 6(4), 225-245. doi:10.1002/wsbm.1270

2013

Fallahi-Sichani, M., Honarnejad, S., Heiser, L. M., Gray, J. W., & Sorger, P. K. (2013). Metrics other than potency reveal systematic variation in responses to cancer drugs. NATURE CHEMICAL BIOLOGY, 9(11), 708-+. doi:10.1038/NCHEMBIO.1337

2012

Fallahi-Sichani, M., Flynn, J. L., Linderman, J. J., & Kirschner, D. E. (2012). Differential Risk of Tuberculosis Reactivation among Anti-TNF Therapies Is Due to Drug Binding Kinetics and Permeability. JOURNAL OF IMMUNOLOGY, 188(7), 3169-3178. doi:10.4049/jimmunol.1103298

Fallahi-Sichani, M., Kirschner, D. E., & Linderman, J. J. (2012). NF-κB signaling dynamics play a key role in infection control in tuberculosis. FRONTIERS IN PHYSIOLOGY, 3. doi:10.3389/fphys.2012.00170

2011

Fallahi-Sichani, M., El-Kebir, M., Marino, S., Kirschner, D. E., & Linderman, J. J. (2011). Multiscale Computational Modeling Reveals a Critical Role for TNF-α Receptor 1 Dynamics in Tuberculosis Granuloma Formation. JOURNAL OF IMMUNOLOGY, 186(6), 3472-3483. doi:10.4049/jimmunol.1003299

2010

Fallahi-Sichani, M., Schaller, M. A., Kirschner, D. E., Kunkel, S. L., & Linderman, J. J. (2010). Identification of Key Processes that Control Tumor Necrosis Factor Availability in a Tuberculosis Granuloma. PLOS COMPUTATIONAL BIOLOGY, 6(5). doi:10.1371/journal.pcbi.1000778