About

Y. Karen Zheng is the George M. Bunker Professor of Management and an Associate Professor of Operations Management at the MIT Sloan School of Management. Her research focuses on the design of incentives, technologies, and behavioral interventions to enhance efficiency, welfare, and sustainability in food and agriculture systems, with a particular emphasis on smallholder value chains. She also investigates the role of information transparency in driving environmentally and socially responsible behaviors. Zheng employs a behavior-centric, data-driven, field-based approach to develop empirically-grounded and practically implementable solutions, collaborating with public and private partners to ensure her research leads to societal and practical impacts. Her work includes designing and implementing innovative market mechanisms, such as a two-stage auction for a major lentil market in Karnataka, India, which resulted in significant profit gains for over 10,000 farmers. Currently, she collaborates with the 2030 Water Resources Group and the World Bank to develop incentive systems for scaling sustainable agricultural practices among smallholders in Uttar Pradesh, India. Zheng holds undergraduate and Master’s degrees from Tsinghua University in China and a PhD from Stanford University.

Research topics

• Biology
• Genetics
• Cell biology

Selected publications

• <i>Nb</i> RD21 protease controls receptor kinase homeostasis in <i>Nicotiana benthamiana</i>

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-26

  articleOpen access

  ABSTRACT RD21-like proteases are papain-like cysteine proteases with a C-terminal granulin domain that are abundant and ubiquitous in angiosperms and have often been implicated in immunity. We previously found that the activity of RD21 in Nicotiana benthamiana ( Nb RD21) is suppressed during infection with Pseudomonas syringae . Here, we studied the role of Nb RD21 in immunity and proteome processing. NbRD21 was disrupted by genome editing and rd21 mutants were subjected to disease assays and shot-gun proteomics. Dipeptide substrate zLR-AMC was used in protease assays and agroinfiltration was used to transiently express Nb RD21 and candidate substrates. Genome edited lines lacking Nb RD21 develop normally but have drastically reduced zLRase activity and are significantly more susceptible to P. syringae . Shot gun proteomics revealed an increased accumulation of ∼20 diverse receptor-like kinases (RLKs) in untreated rd21 knockout lines, but their transcript levels are unaltered when compared to wild-type plants. 35S-driven GFP-tagged RLKs accumulate more upon transient expression in rd21 plants than in wild- type plants. These data indicate that Nb RD21 post-translationally controls RLK homeostasis, either by directly degrading RLKs, or indirectly by regulating endocytic RLK recycling.

  PublisherOA PDFDOI

• Therapeutic Strategies Targeting Aerobic Glycolysis in Cancer and Dynamic Monitoring of Associated Metabolites

  Cells · 2025-08-19 · 7 citations

  reviewOpen access

  Cancer cells predominantly utilize aerobic glycolysis for energy production, preferentially converting glucose (Glu) to pyruvate (PA) and subsequently to lactate (LA). This metabolic reprogramming results in extracellular LA accumulation, acidifying the tumor microenvironment (TME) and facilitating tumor invasion and metastasis. The dynamics of Glu, PA, and LA are pivotal to tumor initiation and progression. This review comprehensively discussed therapeutic strategies targeting these key metabolites and systematically evaluates electrochemical and fluorescence-based techniques for their dynamic monitoring. We highlight the critical role of these monitoring approaches in advancing early cancer diagnosis, enabling personalized treatment, and accelerating anticancer drug development.

  PublisherOA PDFDOI

• Polyphenol oxidase depletion in <i>Nicotiana benthamiana</i> enhances recombinant protein purification and preserves native protein integrity

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-30

  preprintOpen access1st author

  Abstract Agroinfiltration of Nicotiana benthamiana is widely used for recombinant protein production in plant science and molecular pharming, but enzymatic browning and native protein crosslinking during extraction may limit protein integrity and purification efficiency. We generated genome-edited N. benthamiana lines lacking two polyphenol oxidases (PPOs) and analysed protein integrity, enzymatic activity profiles, and recombinant protein purification under non-denaturing extraction conditions. PPO-deficient plants showed reduced browning and native protein crosslinking, preserved endogenous proteins at their predicted molecular weights, displayed increased detectable enzyme activities, and achieved a significantly higher recovery and improved purity of a transiently expressed recombinant protein. These findings identify PPO-mediated oxidation as a major bottleneck during protein extraction and demonstrate that PPO depletion enhances recombinant protein purification while preserving native protein integrity.

  PublisherOA PDFDOI

• Polyphenol oxidase silencing avoids protein cross‐linking and enzymatic browning in <i>Nicotiana benthamiana</i> leaf extracts

  Plant Biotechnology Journal · 2025-06-18 · 6 citations

  articleOpen access

  Browning of extracts during purification of recombinant proteins from agroinfiltrated leaves is a widely observed phenomenon that is commonly quelled with reducing agents and absorbing materials. In fruits and vegetables, browning results from the oxidation of phenolics into brown quinones which react with themselves and other molecules to form a brown melanin-like polymer (Figure 1a, Sui et al., 2023). The oxidation of phenolics is catalysed by polyphenol oxidase (PPO), which is localized to chloroplasts but oxidizes vacuolar phenolics upon cell disruption. Enzymatic browning in sliced apple and bruised potato has been suppressed by silencing PPO (Carter, 2012; González et al., 2020). To prevent browning of extracts from agroinfiltrated leaves, we depleted PPO transcripts by virus-induced gene silencing (VIGS). The N. benthamiana genome (Ranawaka et al., 2023) contains six PPO genes, of which five are predicted to encode putative functional enzymes (Figure 1b). However, only NbL17g16540 is significantly expressed in leaves, and its expression increased upon agroinfiltration (Figure 1c). We cloned a 300 bp fragment to silence NbL17g16540 and its homeolog (NbL10g18390, Figure S1) into RNA2 of the bipartite genome of tobacco rattle virus (TRV). Young N. benthamiana plants were co-agroinoculated with TRV1 and TRV2 carrying fragments of PPO or GUS (β-glucuronidase fragment, negative control). Three weeks post-infiltration, TRV::PPO plants showed no growth or developmental phenotypes compared to TRV::GUS plants (Figure 1d). Western blot analysis of leaf extracts from these plants confirms that PPO was successfully depleted from TRV::PPO plants (Figure 1e). Importantly, cleared leaf extracts of TRV::PPO plants in Tris-buffered saline (TBS) remained green after 4 h of incubation at 4 °C, in contrast to browning observed in extracts of TRV::GUS plants (Figure 1f). When these incubated extracts were separated on protein gels, TRV::PPO samples revealed much stronger signals at 55 kDa, whereas TRV::GUS samples showed high molecular weight (HMW) signals at >180 kDa (Figure 1g). Western blot analysis revealed that much of the large subunit of ribulose bisphosphate carboxylase large chain (RBCL) runs at HMW in the TRV::GUS sample, unlike the 55 kDa signal found in TRV::PPO samples (Figure 1g). This indicates that PPO catalyses cross-linking of RBCL, possibly fixing RBCL tetramers in the multimeric RBCL complex (Duff et al., 2000). The HMW signal was less prominent at the t = 0 time point (Figure 1h), indicating that cross-linking occurs during incubation. To examine the impact of PPO depletion on protein expression and accumulation, we transiently expressed cytoplasmic GFP in TRV::GUS and TRV::PPO plants. Interestingly, extracts from TRV::PPO plants contained significantly higher levels of GFP protein than the TRV::GUS control plants (Figure 1h). Further, the intensity of the GFP signal is reduced in TRV::GUS extracts upon incubation for 4 h at 4 °C but not in TRV::PPO plants. However, we did not detect HMW complexes containing GFP in TRV::GUS control plants (Figure 1h). Measuring GFP fluorescence directly from leaves revealed a significant, 2.8-fold higher GFP fluorescence from TRV::PPO plants when compared to TRV::GUS plants (Figure 1i), consistent with Western blot analysis and supporting the increased GFP accumulation in TRV::PPO plants. Although the underlying mechanism behind the increased transient expression is unclear, this feature might be a valuable additional advantage of PPO silencing. Thus, PPO silencing avoids enzymatic browning and protein cross-linking, and this may increase the yield and quality of purified proteins and improve routinely performed experiments such as co-immunoprecipitation and metabolic experiments. While PPO silencing does not affect plant growth or development, it may reduce immunity to pests and pathogens (Zhang and Sun, 2021). Alternative ways to deplete PPO activity include genome editing, the use of chemical or protein-based inhibitors or physical methods such as those used in the food industry (Sui et al., 2023). We would like to thank Ursula Pyzio for excellent plant care; Felix Homma for supporting RNA-Seq analysis; Sarah Rodgers, Caroline O'Brian and Patricia Bowman for technical support; and George Lomonossoff for providing pEAQ vectors. This project was financially supported by ERC project 101019324 (CH and RH) and BBSRC projects DDT00230 (EW); BB/W013932/1 (SS, KZ and RH) and BB/Y00969X/1 (KZ and RH). RH conceived the project; CM performed most experiments with the help of EW, KZ and SS; RH wrote the manuscript with the help of all authors. None declared. The data that supports the findings of this study are available in the supplementary material of this article. Data S1 Supplemental materials. Table S1 Used plasmids. Table S2 Oligonucleotides. Figure S1 Alignment of VIGS fragment with 6 PPO genes of N. benthamiana. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

  PublisherOA PDFDOI

• Polyphenol oxidase silencing avoids protein crosslinking and enzymatic browning in <i>Nicotiana benthamiana</i> leaf extracts

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-01

  preprintOpen access

  Abstract Oxidation in extracts from agroinfiltrated leaves leads to browning and protein precipitation. Here we show that silencing of polyphenol oxidase (PPO) in Nicotiana benthamiana suppresses enzymatic browning and avoids crosslinking of endogenous proteins such as RuBisCo. PPO silencing does not impact plant growth or development and may also enhance transient gene expression. These results show that depletion of PPO activity could be highly beneficial for plant science applications and molecular pharming.

  PublisherOA PDFDOI

• A real-time ATP biosensor based on gradient porous hollow fiber membrane bioreactor with di-enzyme loading

  Microchemical Journal · 2025-05-17 · 2 citations

  article
  PublisherDOI

• AtDGCR14L contributes to salt‐stress tolerance via regulating pre‐mRNA splicing in Arabidopsis

  The Plant Journal · 2024-11-10 · 1 citations

  articleOpen access

  In plants, pre-mRNA alternative splicing has been demonstrated to be a crucial tier that regulates gene expression in response to salt stress. However, the underlying mechanisms remain elusive. Here, we studied the roles of DIGEORGE-SYNDROME CRITICAL REGION 14-like (AtDGCR14L) in regulating pre-mRNA splicing and salt stress tolerance. We discovered that Arabidopsis AtDGCR14L is required for maintaining plant salt stress tolerance and the constitutively spliced and active isoforms of important stress- and/or abscisic acid (ABA)-responsive genes. We also identified the interaction between AtDGCR14L and splicing factor U1-70k, which needs a highly conserved three amino acid (TWG) motif in DGCR14. Different from wild-type AtDGCR14L, the overexpression of the TWG-substituted AtDGCR14L mutant did not change salt stress tolerance or pre-mRNA splicing of stress/ABA-responsive genes. Additionally, SWITCH3A (SWI3A) is a core subunit of the SWI/SUCROSE NONFERMENTING (SWI/SNF) chromatin-remodeling complexes. We found that SWI3A, whose splicing depends on AtDGCR14L, actively enhances salt stress tolerance. These results revealed that AtDGCR14L may play an essential role in crosstalk between plant salt-stress response and pre-mRNA splicing mechanisms. We also unveiled the potential role of SWI3A in controlling salt stress tolerance. The TWG motif in the intrinsically disordered region of AtDGCR14L is highly conserved and crucial for DGCR14 functions.

  PublisherOA PDFDOI

• The proteome of <i>Nicotiana benthamiana</i> is shaped by extensive protein processing

  New Phytologist · 2024-06-09 · 7 citations

  articleOpen access1st author

  Processing by proteases irreversibly regulates the fate of plant proteins and hampers the production of recombinant proteins in plants, yet only few processing events have been described in agroinfiltrated Nicotiana benthamiana, which has emerged as the main transient protein expression platform in plant science and molecular pharming. Here, we used in-gel digests and mass spectrometry to monitor the migration and topography of 5040 plant proteins within a protein gel. By plotting the peptides over the gel slices, we generated peptographs that reveal where which part of each protein was detected within the protein gel. These data uncovered that 60% of the detected proteins have proteoforms that migrate at lower than predicted molecular weights, implicating extensive proteolytic processing. This analysis confirms the proteolytic removal and degradation of autoinhibitory prodomains of most but not all proteases, and revealed differential processing within pectinemethylesterase and lipase families. This analysis also uncovered intricate processing of glycosidases and uncovered that ectodomain shedding might be common for a diverse range of receptor-like kinases. Transient expression of double-tagged candidate proteins confirmed processing events in vivo. This large proteomic dataset implicates an elaborate proteolytic machinery shaping the proteome of N. benthamiana.

  PublisherOA PDFDOI

• The proteome of agroinfiltrated <i>Nicotiana benthamiana</i> is shaped by extensive protein processing

  bioRxiv (Cold Spring Harbor Laboratory) · 2023-11-04

  preprintOpen access1st author

  Abstract Processing by proteases irreversibly regulates the fate of plant proteins and hampers the production of recombinant protein in plants, yet only few processing events have been described in agroinfiltrated Nicotiana benthamiana , which has emerged as a favorite transient protein expression platform in plant science and molecular pharming. Here, we used in-gel digests and mass spectrometry to monitor the migration and topography of 5,040 plant proteins of agroinfiltrated N. benthamiana within a protein gel. By plotting the peptides over the gel slices, we generated peptographs that reveal where which part of each protein was detected within the protein gel. These data uncovered that 60% of the detected proteins have proteoforms that migrate at lower than predicted molecular weights, implicating extensive proteolytic processing. For instance, this analysis confirms the proteolytic removal and degradation of autoinhibitory prodomains of most but not all proteases, and revealed differential processing within pectinemethylesterase and lipase families. This analysis also uncovered intricate processing of glycosidases and uncovered that ectodomain shedding might be common for a diverse range of receptor-like kinases. Transient expression of double-tagged candidate proteins confirmed various processing events in vivo . This extensive proteomic dataset can be investigated further and demonstrates that most plant proteins are proteolytically processed and implicates an extensive proteolytic machinery shaping the proteome of agroinfiltrated N. benthamiana .

  PublisherOA PDFDOI

• Disruption of <i>CHORISMATE SYNTHASE1</i> leads to yellow-green variegation in soybean leaves

  Journal of Experimental Botany · 2023-04-19 · 7 citations

  article

  Yellow-green variegation leaf phenotype adds more value to ornamental plants, but it is regarded as an undesirable trait in crop plants, affecting their yields. Until recently, the underlying mechanism regulating the yellow-green variegation phenotype has remained largely unexplored in soybean. In the present study, we indentified four Glycine max leaf yellow/green variegation mutants, Gmvar1, Gmvar2, Gmvar3, and Gmvar4, from artificial mutagenesis populations. Map-based cloning, together with the allelic identification test and CRISPR-based gene knockout, proved that mutated GmCS1 controls yellow-green variegation phenotype of the Gmvar mutants. GmCS1 encodes a chorismate synthase in soybean. The content of Phe, Tyr, and Trp were dramatically decreased in Gmcs1 mutants. Exogenous supply of three aromatic amino acid mixtures, or only Phe to Gmvar mutants, leads to recovery of the mutant phenotype. The various biological processes and signalling pathways related to metabolism and biosynthesis were altered in Gmvar mutants. Collectively, our findings provide new insights about the molecular regulatory network of yellow-green variegation leaf phenotype in soybean.

  PublisherDOI

Frequent coauthors

• Neville E. Sanjana

  New York University

  43 shared

• Ophir Shalem

  37 shared

• Shucai Wang

  Linyi University

  31 shared

• David Cox

  University of Milan

  31 shared

• Jonathan S. Gootenberg

  Mass General Brigham

  31 shared

• Feng Zhang

  First Affiliated Hospital of GuangXi Medical University

  29 shared

• Christine S. Cheng

  University of California, San Diego

  27 shared

• Jason Wright

  27 shared

Awards & honors

• MSOM Responsible Research in Operations Management award (20…
• NSF CAREER Award (2015)
• Second Prize in the Institute for Operations Research and th…