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 is interested in 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. The lab prides itself in interdisciplinary focus in biological and quantitative sciences, combined with significant experience leading collaborative teams, and is positioned to tackle complex questions at the intersection of cancer biology, computational bioengineering, and quantitative systems pharmacology.

Highlighted

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.

Paper

aml metabolism risk-classification

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

Oncogeneic receptor activation reconfigures nucleocytoplasmic transport leading to mislocalization of key regulators and early onset of tumorigenesis in breast epithelia.

Paper

breast-cancer systems-biology nucleocytoplasmic-transport tumorigenesis

All

2026

Elevated levels of TNF and its targets characterize better-risk older acute myeloid leukemia patients

Yaseswini Neelamraju, Franck Rapaport, Jorge A. Gandara, B. Bishal Paudel, Susan DeWolf, …, Elisabeth Paietta, Ross Levine, Ari M. Melnick, Stefan Bekiranov, Francine E. Garrett-Bakelman

Leukemia  ·  13 Apr 2026  ·  doi:10.1038/s41375-026-02954-x

CCAAT‐enhancer binding protein delta functions as a tumor suppressor gene in acute myeloid leukemia

Subhash C. Prajapati, Cem Meydan, Yaseswini Neelamraju, Zhenjia Wang, Grant Atwood, …, Christopher E. Mason, Ari M Melnick, Chongzhi Zang, Stefan Bekiranov, Francine E. Garrett-Bakelman

Neoplasia  ·  01 Apr 2026  ·  doi:10.1016/J.NEO.2026.101293

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 Feb 2026  ·  doi:10.1016/j.jbc.2025.111062

We developed an automated image analytical pipeline to process replicative budding events from Microfluidic microscopic images. The pipeline Microfluidic (Micro) Budding Replicative Events Workflow (BREW)–MicroBREW automatically detects and process high-throughput images and results in easy-to-summarize results.

tool yeast pipeline

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 Feb 2026  ·  doi:10.1016/j.bneo.2025.100186

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 Feb 2026  ·  doi:10.1016/J.JBC.2025.111062

2025

Age-dependent topoisomerase I depletion alters recruitment of rDNA silencing complexes

Lindsey N. Power, Natalia Zawrotna, Manikarna Dinda, Abigail E. Weir, Bishal P. Paudel, Oshil Ghimire, Karolina Kisiel, Christopher T. Letai, Kevin A. Janes, Jeffrey S. Smith

openRxiv  ·  01 Aug 2025  ·  doi:10.1101/2025.07.29.667507

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

openRxiv  ·  07 Jun 2025  ·  doi:10.1101/2025.06.06.657881

Paudel BB, Tan S-F, Fox TE, et al. Acute myeloid leukemia stratifies as 2 clinically relevant sphingolipidomic subtypes. Blood Adv . 2024;8(5):1137-1142.

Blood Advances  ·  13 May 2025  ·  doi:10.1182/BLOODADVANCES.2025016279

2024

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

Abstract 4947: Uncovering the molecular basis for clinically relevant sphingolipidomic subtypes in acute myeloid leukemia

B Bishal Paudel, Su-Fern Tan, Johnson Ung, David Claxton, David J. Feith, Thomas P. Loughran, Kevin A. Janes

Cancer Research  ·  22 Mar 2024  ·  doi:10.1158/1538-7445.AM2024-4947

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.

Paper

aml metabolism risk-classification

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  ·  29 Feb 2024  ·  doi:10.1182/BLOODADVANCES.2023010535

2023

Proteome-wide copy-number estimation from transcriptomics

Andrew J. Sweatt, Cameron D. Griffiths, B. Bishal Paudel, Kevin A. Janes

openRxiv  ·  11 Jul 2023  ·  doi:10.1101/2023.07.10.548432

Acute myeloid leukemia stratifies as two clinically relevant sphingolipidomic subtypes

B. Bishal Paudel, Su-Fern Tan, Todd E. Fox, Johnson Ung, Jeremy Shaw, …, Mark Kester, David Claxton, David J. Feith, Kevin A. Janes, Thomas P. Loughran

openRxiv  ·  17 Apr 2023  ·  doi:10.1101/2023.04.13.536805

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

Oncogeneic receptor activation reconfigures nucleocytoplasmic transport leading to mislocalization of key regulators and early onset of tumorigenesis in breast epithelia.

Paper

breast-cancer systems-biology nucleocytoplasmic-transport tumorigenesis

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

Table S4 from An Integrative Gene Expression and Mathematical Flux Balance Analysis Identifies Targetable Redox Vulnerabilities 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

American Association for Cancer Research (AACR)  ·  31 Mar 2023  ·  doi:10.1158/0008-5472.22424584.v1

Table S4 from An Integrative Gene Expression and Mathematical Flux Balance Analysis Identifies Targetable Redox Vulnerabilities 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

American Association for Cancer Research (AACR)  ·  31 Mar 2023  ·  doi:10.1158/0008-5472.22424584

Table S3 from An Integrative Gene Expression and Mathematical Flux Balance Analysis Identifies Targetable Redox Vulnerabilities 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

American Association for Cancer Research (AACR)  ·  31 Mar 2023  ·  doi:10.1158/0008-5472.22424587

Table S3 from An Integrative Gene Expression and Mathematical Flux Balance Analysis Identifies Targetable Redox Vulnerabilities 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

American Association for Cancer Research (AACR)  ·  31 Mar 2023  ·  doi:10.1158/0008-5472.22424587.v1

Supplementary Information from An Integrative Gene Expression and Mathematical Flux Balance Analysis Identifies Targetable Redox Vulnerabilities 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

American Association for Cancer Research (AACR)  ·  31 Mar 2023  ·  doi:10.1158/0008-5472.22424590.v1

Supplementary Information from An Integrative Gene Expression and Mathematical Flux Balance Analysis Identifies Targetable Redox Vulnerabilities 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

American Association for Cancer Research (AACR)  ·  31 Mar 2023  ·  doi:10.1158/0008-5472.22424590

Supplementary Figures from An Integrative Gene Expression and Mathematical Flux Balance Analysis Identifies Targetable Redox Vulnerabilities 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

American Association for Cancer Research (AACR)  ·  31 Mar 2023  ·  doi:10.1158/0008-5472.22424593.v1

Supplementary Figures from An Integrative Gene Expression and Mathematical Flux Balance Analysis Identifies Targetable Redox Vulnerabilities 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

American Association for Cancer Research (AACR)  ·  31 Mar 2023  ·  doi:10.1158/0008-5472.22424593

Data from An Integrative Gene Expression and Mathematical Flux Balance Analysis Identifies Targetable Redox Vulnerabilities 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

American Association for Cancer Research (AACR)  ·  31 Mar 2023  ·  doi:10.1158/0008-5472.c.6511816.v1

Data from An Integrative Gene Expression and Mathematical Flux Balance Analysis Identifies Targetable Redox Vulnerabilities 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

American Association for Cancer Research (AACR)  ·  31 Mar 2023  ·  doi:10.1158/0008-5472.c.6511816

2022

Nucleocytoplasmic transport of active HER2 causes fractional escape from the DCIS-like state

Lixin Wang, B. Bishal Paudel, R. Anthony McKnight, Kevin A. Janes

openRxiv  ·  01 Nov 2022  ·  doi:10.1101/2022.10.30.514440

Heterogeneous, population-level drug-tolerant persisters exhibit ion-channel remodeling and ferroptosis susceptibility

Corey E. Hayford, Blake Baleami, Philip E. Stauffer, B. Bishal Paudel, Aziz Al’Khafaji, Amy Brock, Vito Quaranta, Darren R. Tyson, Leonard A. Harris

openRxiv  ·  05 Feb 2022  ·  doi:10.1101/2022.02.03.479045

2020

An Integrative Gene Expression and Mathematical Flux Balance Analysis Identifies Targetable Redox Vulnerabilities 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

Cancer Research  ·  15 Oct 2020  ·  doi:10.1158/0008-5472.CAN-19-3588

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

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

openRxiv  ·  28 Oct 2019  ·  doi:10.1101/818989

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

openRxiv  ·  17 Oct 2019  ·  doi:10.1101/809889

Dynamics of drug response informs rational combination regimens

B. Bishal Paudel, Vito Quaranta

Science Signaling  ·  20 Aug 2019  ·  doi:10.1126/scisignal.aax9742

Abstract 2894: Overcoming intrinsic resistance to BRAF -inhibitors by modulating redox balance in BRAF -mutated melanoma cells

B. Bishal Paudel, Leonard A. Harris, Keisha N. Hardeman, Corey E. Hayford, Christian T. Meyer, Arwa A. Abugable, Darren R. Tyson, Joshua P. Fessel, Vito Quaranta

Cancer Research  ·  01 Jul 2019  ·  doi:10.1158/1538-7445.AM2019-2894

Abstract 670: Molecular basis of the idling state uncovers vulnerabilities suitable to sequential targeting in melanoma

Corey E. Hayford, Bishal B. Paudel, Leonard A. Harris, Keisha N. Hardeman, Darren R. Tyson, Vito Quaranta

Cancer Research  ·  01 Jul 2019  ·  doi:10.1158/1538-7445.AM2019-670

Abstract 2894: Overcoming intrinsic resistance to BRAF -inhibitors by modulating redox balance in BRAF -mutated melanoma cells

B. Bishal Paudel, Leonard A. Harris, Keisha N. Hardeman, Corey E. Hayford, Christian T. Meyer, Arwa A. Abugable, Darren R. Tyson, Joshua P. Fessel, Vito Quaranta

Cancer Research  ·  01 Jul 2019  ·  doi:10.1158/1538-7445.sabcs18-2894

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

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

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

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

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

Abstract A43: BRAF-mutated melanomas exhibit distinct metabolic programs that may determine therapeutic response

Keisha N. Hardeman, Chengwei Peng, Bishal Paudel, Darren Tyson, Jamey D. Young, Vito Quaranta, Joshua P. Fessel

Molecular Cancer Research  ·  01 Jan 2016  ·  doi:10.1158/1557-3125.metca15-a43

2015

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

2013

Abstract 3403: A stochastically arising subpopulation of B-RafV600E-expressing melanoma continues division in the presence of vemurafenib.

Darren R. Tyson, Chengwei Peng, Keisha N. Hardeman, Bishal Paudel, Vito Quaranta

Cancer Research  ·  01 Apr 2013  ·  doi:10.1158/1538-7445.am2013-3403