P3 Systems Biology Lab Predict, Perturb & Profile Biological Systems

Research

Our research uses a systems bioengineering approach to investigate how aberrant signaling leads to distinct metabolic and epigenetic states, and to devise strategies for therapeutic reprogramming. P3SystemsBiology lab will focus on two main research areas: (1) network-level regulation of metabolic heterogeneity and (2) oncogene-induced alterations in the epigenome and cancer phenotypes. We integrate bioengineering, mechanistic and statistical modeling with single-cell and population-level experiments to identify metabolic vulnerabilities and drivers of early cancer progression. The long-term objective of our research program is to gain a predictive understanding of how dysregulated signaling generates specific metabolic and epigenetic states and how these states can be reprogrammed for therapeutic benefit. Lab prides itself in interdisciplinary focus in biological and quantitative sciences, combined with significant experience leading collaborative teams, and is positioned to tackle these complex questions at the intersection of cancer biology, computational bioengineering, and quantitative systems pharmacology.

All

2025

Age-dependent topoisomerase I depletion alters recruitment of rDNA silencing complexes
Age-dependent topoisomerase I depletion alters recruitment of rDNA silencing complexes
Lindsey N. Power, Natalia Zawrotna, Manikarna Dinda, Abigail E. Weir, B.Bishal Paudel, Oshil Ghimire, Karolina Kisiel, Christopher T. Letai, Kevin A. Janes, Jeffrey S. Smith
Journal of Biological Chemistry  ·  01 Dec 2025  ·  doi:10.1016/j.jbc.2025.111062
The LMO2-LDB1-TAL1 complex regulates transcription networks in Acute Myeloid Leukemia
The LMO2-LDB1-TAL1 complex regulates transcription networks in Acute Myeloid Leukemia
Nicholas Dunham, Zhenjia Wang, Yaseswini Neelamraju, Yan Guo, B. Bishal Paudel, …, Donna S. Neuberg, Stefan Bekiranov, Chongzhi Zang, Utpal P. Davé, Francine E. Garrett-Bakelman
Blood Neoplasia  ·  01 Nov 2025  ·  doi:10.1016/j.bneo.2025.100186
Acid ceramidase inhibition enhances BCL-2 targeting in venetoclax-resistant acute myeloid leukemia via a cytotoxic integrated stress response
Acid ceramidase inhibition enhances BCL-2 targeting in venetoclax-resistant acute myeloid leukemia via a cytotoxic integrated stress response
Johnson Ung, Su-Fern Tan, Jeremy J.P. Shaw, Maansi Taori, Tess M. Deddens, …, Todd E. Fox, David F. Claxton, Charles E. Chalfant, David J. Feith, Thomas P. Loughran
Cold Spring Harbor Laboratory  ·  07 Jun 2025  ·  doi:10.1101/2025.06.06.657881

2024

Proteome-wide copy-number estimation from transcriptomics
Proteome-wide copy-number estimation from transcriptomics
Andrew J Sweatt, Cameron D Griffiths, Sarah M Groves, B Bishal Paudel, Lixin Wang, David F Kashatus, Kevin A Janes
Molecular Systems Biology  ·  27 Sep 2024  ·  doi:10.1038/s44320-024-00064-3
Acute myeloid leukemia stratifies as 2 clinically relevant sphingolipidomic subtypes
Acute myeloid leukemia stratifies as 2 clinically relevant sphingolipidomic subtypes
B. Bishal Paudel, Su-Fern Tan, Todd E. Fox, Johnson Ung, Upendarrao Golla, …, Mark Kester, David J. Feith, David Claxton, Kevin A. Janes, Thomas P. Loughran
Blood Advances  ·  01 Mar 2024  ·  doi:10.1182/bloodadvances.2023010535
Biochemical and metabolic profiling integrated with current AML risk classifiers identifies distinct molecular subtypes with differential drug sensitivities.

2023

Nucleocytoplasmic transport of active HER2 causes fractional escape from the DCIS-like state
Nucleocytoplasmic transport of active HER2 causes fractional escape from the DCIS-like state
Lixin Wang, B. Bishal Paudel, R. Anthony McKnight, Kevin A. Janes
Nature Communications  ·  13 Apr 2023  ·  doi:10.1038/s41467-023-37914-x

2022

A heterogeneous drug tolerant persister state in BRAF-mutant melanoma is characterized by ion channel dysregulation and susceptibility to ferroptosis
A heterogeneous drug tolerant persister state in BRAF-mutant melanoma is characterized by ion channel dysregulation and susceptibility to ferroptosis
Corey E. Hayford, Philip E. Stauffer, Blake Baleami, B. Bishal Paudel, Darren R. Tyson, Aziz Al’Khafaji, Kaitlyn E. Johnson, Leonard A. Harris, Amy Brock, Vito Quaranta
Cold Spring Harbor Laboratory  ·  05 Feb 2022  ·  doi:10.1101/2022.02.03.479045

2020

Drug-Tolerant Idling Melanoma Cells Exhibit Theory-Predicted Metabolic Low-Low Phenotype
Drug-Tolerant Idling Melanoma Cells Exhibit Theory-Predicted Metabolic Low-Low Phenotype
Dongya Jia, B. Bishal Paudel, Corey E. Hayford, Keisha N. Hardeman, Herbert Levine, José N. Onuchic, Vito Quaranta
Frontiers in Oncology  ·  14 Aug 2020  ·  doi:10.3389/fonc.2020.01426

2019

Disruption of Redox Balance Enhances the Effects of BRAF-inhibition in Melanoma Cells
Disruption of Redox Balance Enhances the Effects of BRAF-inhibition in Melanoma Cells
B. Bishal Paudel, Joshua E. Lewis, Keisha N. Hardeman, Corey E. Hayford, Charles J. Robbins, Simona G. Codreanu, Stacy D. Sherrod, John A. McLean, Melissa L. Kemp, Vito Quaranta
Cold Spring Harbor Laboratory  ·  28 Oct 2019  ·  doi:10.1101/818989
Dynamics of drug response informs rational combination regimens
Dynamics of drug response informs rational combination regimens
B. Bishal Paudel, Vito Quaranta
Science Signaling  ·  20 Aug 2019  ·  doi:10.1126/scisignal.aax9742
Metabolic plasticity meets gene regulation
Metabolic plasticity meets gene regulation
B. Bishal Paudel, Vito Quaranta
Proceedings of the National Academy of Sciences  ·  08 Feb 2019  ·  doi:10.1073/pnas.1900169116
Quantifying Drug Combination Synergy along Potency and Efficacy Axes
Quantifying Drug Combination Synergy along Potency and Efficacy Axes
Christian T. Meyer, David J. Wooten, B. Bishal Paudel, Joshua Bauer, Keisha N. Hardeman, David Westover, Christine M. Lovly, Leonard A. Harris, Darren R. Tyson, Vito Quaranta
Cell Systems  ·  01 Feb 2019  ·  doi:10.1016/j.cels.2019.01.003

2018

A Nonquiescent Idling Population State in Drug-Treated, BRAF-Mutated Melanoma
A Nonquiescent “Idling” Population State in Drug-Treated, BRAF-Mutated Melanoma
B. Bishal Paudel, Leonard A. Harris, Keisha N. Hardeman, Arwa A. Abugable, Corey E. Hayford, Darren R. Tyson, Vito Quaranta
Biophysical Journal  ·  01 Mar 2018  ·  doi:10.1016/j.bpj.2018.01.016

2017

Dependence On Glycolysis Sensitizes BRAF-mutated Melanomas For Increased Response To Targeted BRAF Inhibition
Dependence On Glycolysis Sensitizes BRAF-mutated Melanomas For Increased Response To Targeted BRAF Inhibition
Keisha N. Hardeman, Chengwei Peng, Bishal B. Paudel, Christian T. Meyer, Thong Luong, Darren R. Tyson, Jamey D. Young, Vito Quaranta, Joshua P. Fessel
Scientific Reports  ·  16 Feb 2017  ·  doi:10.1038/srep42604

2016

An unbiased metric of antiproliferative drug effect in vitro
An unbiased metric of antiproliferative drug effect in vitro
Leonard A Harris, Peter L Frick, Shawn P Garbett, Keisha N Hardeman, B Bishal Paudel, Carlos F Lopez, Vito Quaranta, Darren R Tyson
Nature Methods  ·  02 May 2016  ·  doi:10.1038/nmeth.3852

2015

Quantifying heterogeneity and dynamics of clonal fitness in response to perturbation
Quantifying heterogeneity and dynamics of clonal fitness in response to perturbation
Peter L. Frick, Bishal B. Paudel, Darren R. Tyson, Vito Quaranta
Journal of Cellular Physiology  ·  27 Mar 2015  ·  doi:10.1002/jcp.24888