About

Steven Banik is an Assistant Professor of Chemistry at Stanford University whose research interests focus on rewiring mammalian biology and chemical biotechnology development through molecular design and construction. His lab combines chemical biology, organic chemistry, protein engineering, cell, and molecular biology to precisely manipulate biological machines in mammalian cells. The projects aim to perform new functions that shed light on regulatory machinery and explore the potential scope of mammalian biology, with a particular focus on studying biological mechanisms that can be coopted by synthetic molecules, including small molecules and proteins. These concepts are applied to develop new therapeutic strategies for aging-related disorders, genetic diseases, and cancer. Prior to joining Stanford's faculty, Steven Banik was a NIH and Burroughs CASI postdoctoral fellow advised by Prof. Carolyn Bertozzi at Stanford, where he developed approaches for targeted protein degradation from the extracellular space using lysosome targeting chimeras (LYTACs). He earned his Ph.D. from Harvard University in 2016, working with Prof. Eric Jacobsen on synthetic methods for the selective, catalytic difluorination of organic molecules and new approaches for generating and controlling reactive cationic intermediates in asymmetric catalysis. His educational background includes a B.S. in Chemistry from the University of Wisconsin–Madison in 2011 and a postdoctoral fellowship at Stanford University in Chemical Biology.

Research topics

• Chemistry
• Biochemistry
• Biology
• Cell biology
• Internal medicine
• Medicine
• Endocrinology

Selected publications

• Improved protein binder design using β-pairing targeted RFdiffusion

  Nature Communications · 2026-01-10 · 2 citations

  articleOpen access

  Designing proteins that bind with high affinity to hydrophilic protein target sites remains a challenging problem. Here we show that RFdiffusion can be conditioned to generate protein scaffolds that form geometrically matched extended β-sheets with target protein edge β-strands in which polar groups on the target are complemented with hydrogen bonding groups on the design. We use this approach to design binders against edge-strand target sites on KIT, PDGFRɑ, ALK-2, ALK-3, FCRL5, NRP1, and α-CTX, and obtain higher (pM to mid nM) affinities and success rates than unconditioned RFdiffusion. Despite sharing β-strand interactions, designs have high specificity, reflecting the precise customization of interacting β-strand geometry and additional designed binder-target interactions. A binder-KIT co-crystal structure is nearly identical to the design model, confirming the accuracy of the design approach. The ability to robustly generate binders to the hydrophilic interaction surfaces of exposed β-strands considerably increases the range of computational binder design. This study demonstrates the capability of deep learning protein design models in generating functionally validated β-strand pairing interfaces, expanding the structural diversity of de novo binding proteins and accessible target surfaces.

  PublisherOA PDFDOI

• Improved protein binder design using β-pairing targeted RFdiffusion

  DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron) · 2026-01-01

  articleOpen access

  Designing proteins that bind with high affinity to hydrophilic protein target sites remains a challenging problem. Here we show that RFdiffusion can be conditioned to generate protein scaffolds that form geometrically matched extended β-sheets with target protein edge β-strands in which polar groups on the target are complemented with hydrogen bonding groups on the design. We use this approach to design binders against edge-strand target sites on KIT, PDGFRɑ, ALK-2, ALK-3, FCRL5, NRP1, and α-CTX, and obtain higher (pM to mid nM) affinities and success rates than unconditioned RFdiffusion. Despite sharing β-strand interactions, designs have high specificity, reflecting the precise customization of interacting β-strand geometry and additional designed binder-target interactions. A binder-KIT co-crystal structure is nearly identical to the design model, confirming the accuracy of the design approach. The ability to robustly generate binders to the hydrophilic interaction surfaces of exposed β-strands considerably increases the range of computational binder design.

  PublisherDOI

• Programmed Manipulation of RNA Targets By Human Argonaute 2

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-02

  articleOpen accessSenior authorCorresponding

  Abstract Nucleic acid manipulation using programmable ribonucleoprotein complexes (RNPs) has enabled transformative research tools and led to new therapeutic strategies. RNA directly regulates diverse cellular processes, 1 is a crucial mediator of protein synthesis, and offers advantages in therapeutic targeting and fundamental discovery complementary to those of DNA. 2 ISC- 3 and Cas-based 4,5 scaffolds where the RNP is fused to an effector protein can alter RNA sequence, structure, and function. However, the non-human origins underlying these systems create challenges in therapeutic translation and the presence of non-native proteins can have unintended and little understood effects on cells. 6–8 Systematic repurposing of human proteins, which have been optimized in the cellular environment by evolution, for expanded programmable functions could reveal new biological principles and bypass the limitations of foreign proteins. Here, we demonstrate that the catalytic engine of the RNA-interference (RNAi) pathway, human Argonaute 2 (AGO2), 9,10 can be repurposed as a modular targeting domain, and when fused to a C-to-U deaminase, enable AGO-Led Targeted Editing of RNA (ALTER). Using guide RNAs which remodel target RNA structure for selective editing and reduced nuclease activity, we show that ALTER can act on a variety of target transcripts including endogenous mRNAs and lncRNAs, with activities comparable or exceeding those of Cas-based systems. 11,12 Despite its human origin and role in RNAi, transcriptome-wide RNAseq revealed lower levels of off-target editing compared to Cas-based editing systems. These results demonstrate that AGO2 can be rationally redirected from RNAi to a broader spectrum of RNA manipulations, establishing that intact human proteins can be reconfigured for expanded molecular function.

  PublisherOA PDFDOI

• Generating Surprisingly Powerful Pharmacology from Chemically Induced Protein Interactions

  Accounts of Chemical Research · 2025-07-24 · 3 citations

  review

  Small molecules that induce proximity between proteins have transformed our ability to manipulate and study cellular processes. Beyond this, proximity-inducing small molecules and biologics are now a clinical reality with increasing reach over different targets and disease indications, benefiting from our rapidly expanding abilities to exploit diverse biochemical mechanisms and being powered by emerging design principles. Targeted protein degradation has become a predominant proximity-dependent therapeutic mechanism. We contend that there are many yet-unexplored pharmacologically useful mechanisms that can be triggered by chemically induced protein interactions. We discuss the general principles of proximity pharmacology and highlight two areas we believe are ripe for innovation.

  PublisherDOI

• Improved protein binder design using beta-pairing targeted RFdiffusion

  Research Square · 2025-01-16 · 3 citations

  preprintOpen access
  PublisherOA PDFDOI

• A secondary β-hydroxybutyrate metabolic pathway linked to energy balance

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-09-09

  preprintOpen access

  β-hydroxybutyrate (BHB) is an abundant ketone body. To date, all known pathways of BHB metabolism involve interconversion of BHB and primary energy intermediates. Here we show that CNDP2 controls a previously undescribed secondary BHB metabolic pathway via enzymatic conjugation of BHB and free amino acids. This BHB-ylation reaction produces a family of endogenous ketone metabolites, the BHB-amino acids. Genetic ablation of CNDP2 in mice eliminates tissue amino acid BHB-ylation activity and reduces BHB-amino acid levels. Administration of BHB-Phe, the most abundant BHB-amino acid, to obese mice activates neural populations in the hypothalamus and brainstem and suppresses feeding and body weight. Conversely, CNDP2-KO mice exhibit increased food intake and body weight upon ketosis stimuli. CNDP2-dependent amino acid BHB-ylation and BHB-amino acid metabolites are also conserved in humans. Therefore, the metabolic pathways of BHB extend beyond primary metabolism and include secondary ketone metabolites linked to energy balance.

  PublisherDOI

• A β-hydroxybutyrate shunt pathway generates anti-obesity ketone metabolites

  Cell · 2024-11-12 · 57 citations

  articleOpen access

  β-Hydroxybutyrate (BHB) is an abundant ketone body. To date, all known pathways of BHB metabolism involve the interconversion of BHB and primary energy intermediates. Here, we identify a previously undescribed BHB secondary metabolic pathway via CNDP2-dependent enzymatic conjugation of BHB and free amino acids. This BHB shunt pathway generates a family of anti-obesity ketone metabolites, the BHB-amino acids. Genetic ablation of CNDP2 in mice eliminates tissue amino acid BHB-ylation activity and reduces BHB-amino acid levels. The most abundant BHB-amino acid, BHB-Phe, is a ketosis-inducible congener of Lac-Phe that activates hypothalamic and brainstem neurons and suppresses feeding. Conversely, CNDP2-KO mice exhibit increased food intake and body weight following exogenous ketone ester supplementation or a ketogenic diet. CNDP2-dependent amino acid BHB-ylation and BHB-amino acid metabolites are also conserved in humans. Therefore, enzymatic amino acid BHB-ylation defines a ketone shunt pathway and bioactive ketone metabolites linked to energy balance.

  PublisherDOI

• Molecular glues and induced proximity: An evolution of tools and discovery

  Cell chemical biology · 2024-04-29 · 43 citations

  articleSenior authorCorresponding
  PublisherDOI

• Targeted protein relocalization via protein transport coupling

  Nature · 2024-09-18 · 43 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Improved protein binder design using beta-pairing targeted RFdiffusion

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-10-12 · 16 citations

  preprintOpen access

  Abstract Despite recent advances in the computational design of protein binders, designing proteins that bind with high affinity to polar protein targets remains an outstanding problem. Here we show that RFdiffusion can be conditioned to efficiently generate protein scaffolds that form geometrically matched extended beta-sheets with target protein edge beta-strands in which polar groups on the target are nearly perfectly complemented with hydrogen bonding groups on the design. We use this approach to design binders against a set of therapeutically relevant polar targets (KIT, PDGFRɑ, ALK-2, ALK-3, FCRL5, and NRP1) and find that beta-strand-targeted design yields higher affinities and success rates than unconditioned RFdiffusion. All by all binding experiments show that the designs have affinities ranging from 137 pM to mid nM for their targets and essentially no off target binding despite the sharing of beta-strand interactions, likely reflecting the precise customization of interacting beta-strand geometry and additional designed binder-target interactions. A co-crystal structure of one such design in complex with the KIT receptor is nearly identical to the computational design model confirming the accuracy of the design approach. The ability to robustly generate binders displaying high affinity and specificity to polar interaction surfaces with exposed beta-strands considerably increases the range and capabilities of computational binder design.

  PublisherOA PDFDOI

Frequent coauthors

• Eric N. Jacobsen

  Harvard University Press

  38 shared

• Carolyn R. Bertozzi

  Stanford University

  23 shared

• Jonathan William Medley

  16 shared

• Katrina M. Mennie

  Merck & Co., Inc., Rahway, NJ, USA (United States)

  14 shared

• Elaine C. Reichert

  Massachusetts Institute of Technology

  8 shared

• Nicholas M. Riley

  University of Washington

  8 shared

• Green Ahn

  University of Washington

  7 shared

• Jonathan Z. Long

  Stanford University

  6 shared

Labs

• Vice Provost for Student AffairsPI