Hyunbum Jang
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View article: Discovering anticancer drug target combinations via network-informed signaling-based approach
Discovering anticancer drug target combinations via network-informed signaling-based approach Open
Our network-based approach discovers optimal protein co-target combinations to counter resistance, selecting co-targets from alternative pathways and their connectors.
View article: Allostery in Biomolecular Condensates
Allostery in Biomolecular Condensates Open
Allosteric proteins and membrane-less biomolecular condensates are physics-governed pivotal functional components. Allosteric regulation is an inherent physical property of dynamic proteins, and dynamic proteins are allosteric. Thus, in bi…
View article: How residence time works in allosteric drugs
How residence time works in allosteric drugs Open
Drug residence time defines the duration the drug is bound to its protein target. It is a crucial determinant of drug action. Yet, a priori estimating it in the design could be the most challenging. The mechanisms of allosteric and orthost…
View article: Mutations in tumor signaling, metastases, and synthetic lethality establish distinct patterns
Mutations in tumor signaling, metastases, and synthetic lethality establish distinct patterns Open
Effective identification of oncogenic mutations is essential for diagnosis, forecasting resistance, and metastasis in remission. It is required for an optimal drug regimen. We develop a framework to discover mutations that co-exist in diff…
View article: Oncogenic PI3Kα variants reveal graded conformational spectrum with mutation-specific cryptic pockets
Oncogenic PI3Kα variants reveal graded conformational spectrum with mutation-specific cryptic pockets Open
Cancer-prone alleles exhibit single hotspot mutations. However, the combination of a cancer hotspot and a weak or moderate mutation (the ‘one-two punch’ hypothesis) produces same-allele double variants with a significantly different and po…
View article: Drug resistance and tumor heterogeneity: cells and ensembles
Drug resistance and tumor heterogeneity: cells and ensembles Open
View article: Tumors and their microenvironments: Learning from pediatric brain pathologies
Tumors and their microenvironments: Learning from pediatric brain pathologies Open
View article: ERK Allosteric Activation: The Importance of Two Ordered Phosphorylation Events
ERK Allosteric Activation: The Importance of Two Ordered Phosphorylation Events Open
View article: Distinct Allosteric Networks in CDK4 and CDK6 in the Cell Cycle and in Drug Resistance
Distinct Allosteric Networks in CDK4 and CDK6 in the Cell Cycle and in Drug Resistance Open
View article: AT1R and Integrin β3 Synergize to Drive Aortic Dissection via Non-Canonical Wnt/β-Catenin Signaling
AT1R and Integrin β3 Synergize to Drive Aortic Dissection via Non-Canonical Wnt/β-Catenin Signaling Open
Aortic dissection (AD), a life-threatening cardiovascular emergency, continues to impose high mortality due to insufficient therapeutic options, as monotherapy targeting angiotensin II type 1 receptor (AT1R) demonstrates limited clinical e…
View article: Distinct allosteric networks in CDK4 and CDK6 in the cell cycle and in drug resistance
Distinct allosteric networks in CDK4 and CDK6 in the cell cycle and in drug resistance Open
Cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) are key regulators of the G1-S phase transition in the cell cycle. In cancer cells, CDK6 overexpression often outcompetes CDK4 in driving cell cycle progression, contributing to resistance a…
View article: ERK Allosteric Activation: The Importance of Two Ordered Phosphorylation Events
ERK Allosteric Activation: The Importance of Two Ordered Phosphorylation Events Open
ERK, a coveted proliferation drug target, is a pivotal kinase in the Ras/ERK signaling cascade. Despite this, crucial questions about its activation have not been fully explored on the foundational, conformational level. Such questions inc…
View article: Allostery in Disease: Anticancer Drugs, Pockets, and the Tumor Heterogeneity Challenge
Allostery in Disease: Anticancer Drugs, Pockets, and the Tumor Heterogeneity Challenge Open
View article: Molecular principles underlying aggressive cancers
Molecular principles underlying aggressive cancers Open
Aggressive tumors pose ultra-challenges to drug resistance. Anti-cancer treatments are often unsuccessful, and single-cell technologies to rein drug resistance mechanisms are still fruitless. The National Cancer Institute defines aggressiv…
View article: Allosteric modulation of <scp>NF1 GAP</scp>: Differential distributions of catalytically competent populations in loss‐of‐function and gain‐of‐function mutants
Allosteric modulation of <span>NF1 GAP</span>: Differential distributions of catalytically competent populations in loss‐of‐function and gain‐of‐function mutants Open
Neurofibromin (NF1), a Ras GTPase‐activating protein (GAP), catalyzes Ras‐mediated GTP hydrolysis and thereby negatively regulates the Ras/MAPK pathway. NF1 mutations can cause neurofibromatosis type 1 manifesting tumors, and neurodevelopm…
View article: mTOR Variants Activation Discovers PI3K-like Cryptic Pocket, Expanding Allosteric, Mutant-Selective Inhibitor Designs
mTOR Variants Activation Discovers PI3K-like Cryptic Pocket, Expanding Allosteric, Mutant-Selective Inhibitor Designs Open
mTOR plays a crucial role in PI3K/AKT/mTOR signaling. We hypothesized that mTOR activation mechanisms driving oncogenesis can advise effective therapeutic designs. To test this, we combined cancer genomic analysis with extensive molecular …
View article: M-Ras distinct activation scenarios: A mechanistic outlook and targeting
M-Ras distinct activation scenarios: A mechanistic outlook and targeting Open
The conformational states of canonical Ras (H-, K-, and N-Ras) GTPases define their nucleotide-exchange and effector binding capabilities. M-Ras, whose mutational variants can cause cancer directly, and indirectly through their complexes, …
View article: Kinase signaling cascades: an updated mechanistic landscape
Kinase signaling cascades: an updated mechanistic landscape Open
In the MAPK and PI3K pathways, upstream kinases Raf, MEK, and PI3K have one primary substrate, while downstream kinases ERK, AKT, and mTOR have multiple substrates. Mutations in PI3K/AKT/mTOR kinases are more abundant than mutations in MAP…
View article: Ras, RhoA, and vascular pharmacology in neurodevelopment and aging
Ras, RhoA, and vascular pharmacology in neurodevelopment and aging Open
View article: mTOR variants activation discovers PI3K-like cryptic pocket, expanding allosteric, mutant-selective inhibitor designs
mTOR variants activation discovers PI3K-like cryptic pocket, expanding allosteric, mutant-selective inhibitor designs Open
mTOR plays a crucial role in PI3K/AKT/mTOR signaling. We hypothesized that mTOR activation mechanisms driving oncogenesis can advise effective therapeutic designs. To test this, we combined cancer genomic analysis with extensive molecular …
View article: Anticancer Target Combinations: Network-Informed Signaling-Based Approach to Discovery
Anticancer Target Combinations: Network-Informed Signaling-Based Approach to Discovery Open
While anticancer drug discovery has seen dramatic innovations and successes, sequential single therapies are time-limited by resistance, and combinatorial strategies have been lagging. The number of possible drug combinations is vast. To s…
View article: Capturing Autoinhibited PDK1 Reveals the Linker’s Regulatory Role, Informing Innovative Inhibitor Design
Capturing Autoinhibited PDK1 Reveals the Linker’s Regulatory Role, Informing Innovative Inhibitor Design Open
PDK1 is crucial for PI3K/AKT/mTOR and Ras/MAPK cancer signaling. It phosphorylates AKT in a PIP3-dependent but S6K, SGK, and RSK kinases in a PIP3-independent manner. Unlike its substrates, its autoinhibited monomeric…
View article: Tumor-derived RHOA mutants interact with effectors in the GDP-bound state
Tumor-derived RHOA mutants interact with effectors in the GDP-bound state Open
RHOA mutations are found at diverse residues in various cancer types, implying mutation- and cell-specific mechanisms of tumorigenesis. Here, we focus on the underlying mechanisms of two gain-of-function RHOA mutations, A161P and A161V, id…
View article: The value of protein allostery in rational anticancer drug design: an update
The value of protein allostery in rational anticancer drug design: an update Open
To select a productive venue in allosteric inhibitor development, we should learn from nature. Currently, useful strategies follow this route. Consider, for example, the mechanisms exploited in relieving autoinhibition and in harnessing al…
View article: Single cell spatial biology over developmental time can decipher pediatric brain pathologies
Single cell spatial biology over developmental time can decipher pediatric brain pathologies Open
Pediatric low grade brain tumors and neurodevelopmental disorders share proteins, signaling pathways, and networks. They also share germline mutations and an impaired prenatal differentiation origin. They may differ in the timing of the ev…
View article: Mitogen signaling strength and duration can control cell cycle decisions
Mitogen signaling strength and duration can control cell cycle decisions Open
Decades ago, mitogen-promoted signaling duration and strength were observed to be sensed by the cell and to be critical for its decisions: to proliferate or differentiate. Landmark publications established the importance of mitogen signali…
View article: Review: Cancer and neurodevelopmental disorders: multi-scale reasoning and computational guide
Review: Cancer and neurodevelopmental disorders: multi-scale reasoning and computational guide Open
The connection and causality between cancer and neurodevelopmental disorders have been puzzling. How can the same cellular pathways, proteins, and mutations lead to pathologies with vastly different clinical presentations? And why do indiv…
View article: K128 ubiquitination constrains RAS activity by expanding its binding interface with GAP proteins
K128 ubiquitination constrains RAS activity by expanding its binding interface with GAP proteins Open
View article: Anticancer drugs: How to select small molecule combinations?
Anticancer drugs: How to select small molecule combinations? Open
View article: CDK2 and CDK4: Cell Cycle Functions Evolve Distinct, Catalysis-Competent Conformations, Offering Drug Targets
CDK2 and CDK4: Cell Cycle Functions Evolve Distinct, Catalysis-Competent Conformations, Offering Drug Targets Open
Cyclin-dependent kinases (CDKs), particularly CDK4 and CDK2, are crucial for cell cycle progression from the Gap 1 (G1) to the Synthesis (S) phase by phosphorylating targets such as the Retinoblastoma Protein (Rb). CDK4, paired with cyclin…